About the Authors

In 2004, Randy A. Albrecht was recruited by Dr. Adolfo Garcia- Sastre as a postdoctoral fellow in the Department of Microbiology and is a member of the Global Health and Emerging Pathogens Institute at the Icahn School of Medicine at Mount Sinai in New York. Dr. Albrecht is currently an associate professor in the Department of Microbiology and is a member of the Global Health and Emerging Pathogens Institute at the Icahn School of Medicine at Mount Sinai. His research interests focus on host-pathogen interactions involving respiratory viruses, developing animal models of disease, and developing vaccines against respiratory viruses. His research is currently supported by funding from the National Institutes of Health.

Ste´phanie Anchisi started working on innate immunity sensing of RNA viruses as a graduate student with Dominique Garcin at the University of Geneva. In 2015, she started her postdoctoral research work on host proteins involved in inﬂuenza virus entry with Pr. Mirco Schmolke and Pr. Laurent Kaiser. From Geneva, Switzerland.

Wendy S. Barclay received her first degree from the University of Cambridge and her PhD from the University of Reading, conduct- ing research at the Common Cold Unit on the immune response to rhinovirus. She worked as a postdoctoral fellow in the laboratories of Professor Jeffrey Almond at the University of Reading, studying poliovirus replication, and Professor Peter Palese at Mount Sinai Medical Center, New York, where she developed reverse genetics technology for influenza B virus. In 1995 she returned to the UK to take up a lectureship at the University of Reading. In 2007 she moved to Imperial College London where she conducts research into the interaction of influenza viruses with their hosts.

Jessica A. Belser is a microbiologist in the Immunology and Path- ogenesis Branch of CDC’s Inﬂuenza Division. She studies the pathogenicity, transmissibility, and tropism of emerging inﬂuenza viruses, notably those within the H7 subtype. She is a recipient of the 2012 Presidential Early Career Award for Scientists and Engi- neers (PECASE) and the Charles C. Shepard Award.

Amar R. Bhagwat is an optical physicist by training and completed his doctoral dissertation in applied physics with Dr. Alexander Gaeta at Cornell University, where he investigated low-light-level nonlinear optical phenomena in atomic systems. During his postdoctoral training at the University of Michigan, he became interested in developing new techniques for imaging live biological systems. Currently, he is a research assistant professor in the group of Dr. Seema Lakdawala at the University of Pittsburgh studying cellular transport of inﬂuenza viruses using light-sheet microscopy. He is from Mumbai, India.

Christin Bruchhagen first joined the lab of Christina Ehrhardt as a practical student investigating the molecular basis of influenza-host interactions and then moved to the field of viral and bacterial super- infections for her master’s thesis in 2013. Since 2014 she continues the research of pathogen-host interactions in the context of influenza and S. aureus super-infections as a PhD student. Her work is currently funded by the University of Mu¨nster (IMF-EH121307).

Arturo Casadevall, MD, PhD, is Bloomberg Distinguished Pro- fessor and Chair of the W. Harry Feinstone Department of Molec- ular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health. Dr. Casadevall’s major research interests are in fungal pathogenesis and the mechanisms of antibody action. In the area of biodefense, he has an active research program to understand the mechanisms of antibody- mediated neutralization of Bacillus anthracis toxins. Dr. Casadevall is the editor-in-chief of mBio, the ﬁrst open access general journal of the American Society of Microbiology and is on About the Authors 635 the editorial board of several journals including the Journal of Infectious Diseases and the Journal of Experimental Medicine.He has also served in numerous NIH committees including those that drafted the NIAID Strategic Plan and the Blue Ribbon Panel on Biodefense Research. He served on the National Academy of Sciences panel that reviewed the science on the FBI investigation of the anthrax terror attacks of 2001, the National Science Advisory Board for Biosecurity from 2005 to 2014 and from 2015 to 2017, and as a Commissioner to the National Commission on Forensic Science, the United States Department of Justice.

Isabel Ferna´ndez de Castro obtained her PhD in biology from the Complutense University of Madrid in 2014. In 2010 she joined the Cell Structure Laboratory (CSL) of the National Biotechnology Center where she developed her PhD project. In 2012 she worked at the Plant Pathology Department, University of Kentucky, USA. She is currently a postdoctoral scientist in the CSL. Dr. Ferna´ndez de Castro uses advanced light and electron microscopy methods to investigate the biogenesis and architecture of viral factories assem- bled by RNA viruses.

Yi-ying Chou got into the world of virology during her undergraduate study at National Taiwan University. She was intrigued by the complexity of inﬂuenza viruses and started working on the molecular biology and transmissions of inﬂuenza viruses as a graduate student with Dr. Peter Palese at Icahn School of Medicine at Mount Sinai. In 2013, she moved to Boston to join Dr. Tom Kirchhausen’s group at Harvard Medical School to study the entry mechanisms of various viruses using real-time imaging techniques.

Samuel Cordey conducted his PhD in the laboratory of Professor Laurent Roux from the University of Geneva. In 2007, he joined the Professor Laurent Kaiser’s group in the University Hospitals of Geneva. Its main activities focus on the fundamental and translational virology research, development of new diagnostic tools, and supervision of routine laboratory analyzes. Since 2014, he is in charge of the Swiss National Inﬂuenza Center. 636 About the Authors

Michel Crameri joined the Institute of Medical Virology at the University of Zurich (Switzerland) in 2012. He completed his master’s studies in PD Dr. Jovan Pavlovic’s lab, focusing on the interference of inﬂuenza A viruses with the cellular innate immune response. Since 2013, he is a PhD student in the group of PD Dr. Jovan Pavlovic, working on speciﬁc aspects of innate immunity against herpesviruses.

Hannah M. Creager conducted her graduate research in the Microbiology and Molecular Genetics program at Emory Univer- sity as a guest researcher in the Inﬂuenza Division at the Centers for Disease Control and Prevention (CDC). Her research has explored inﬂuenza virus tropism in respiratory and ocular cells, employing the aerosol-based inoculation method described in the protocol chapter.

Anthony T. DiPiazza graduated with a BS in biology from the University of Maryland, College Park in 2010. After completion of a research fellowship at the Food and Drug Administration, Anthony matriculated into the Microbiology and Immunology doctoral program at the University of Rochester in 2011, completing his MS in 2014 with a focus on virus-speciﬁc immune responses. Anthony is currently completing his doctoral dissertation research regarding the role of CD4 T cells in protective immunity to inﬂuenza viruses under the guidance of Dr. Andrea J. Sant.

Christina Ehrhardt received her PhD from Wu¨rzburg University, Germany, where she studied the host signaling pathways that are induced upon inﬂuenza virus infections and that lead to kinase activation and cytokine expression. In 2005 she moved to the Institute of Virology at the University of Mu¨nster headed by Ste- phan Ludwig to set up a research group. Recent projects aim to unravel basic molecular-biological principles that underlie the establishment, dynamics, and functional complexity not only of inﬂuenza viruses but also of bacterial co-infections. Her research About the Authors 637 is currently supported by the University of Mu¨nster (IMF-EH121307; IZKF-EhC2/006/15) and the Deutsche For- schungsgemeinschaft (SFB1009/B02).

Shufang Fan received her PhD from the Graduate School of the Chinese Agricultural Academy of Science (CAAS) and was trained in influenza virology by Dr. Hualan Chen at Harbin Veterinary Research Institute. She is presently an Assistant Scientist in Dr. Kawaoka’s group. She has identified several amino acid residues that affect the pathogenicity of highly pathogenic H5N1 influenza viruses in mammals. Her current research focuses on the isolation and characterization of antigenic escape variants, and on testing the antiviral activity of small molecule compounds that she identified through systems biology approaches.

Evelyn Fessler was born on March 25, 1987, in Laupheim, Ger- many. She studied molecular medicine at the Friedrich-Alexander University Erlangen-Nuremberg and completed her studies with her undergraduate thesis work performed in the laboratory of Dr. Robert Weinberg at the Whitehead Institute in Cambridge. For her PhD she joined the laboratory of Dr. Jan Paul Medema at the Academic Medical Center in Amsterdam. After her graduation, she moved to Munich where she is now working as a postdoc in the laboratory of Dr. Lucas Jae at the Gene Center.

Adam Finn is professor of pediatrics at the University of Bristol, UK. He studied Medical Sciences at Cambridge University and then moved to University of Oxford Medical School to complete his clinical degree in 1983. After qualifying he did training jobs in pediatrics in Shefﬁeld, Bristol, and Guy’s Hospital London before taking up a fellowship in Infectious Diseases at the Children’s Hospital of Philadelphia in 1987. He completed his academic training as Lecturer in Immunology at the Institute of Child Health, Great Ormond St, London, where he wrote his PhD. In 1992, he took up a senior lecturer position at the University of Shefﬁeld, UK. Over the following 9 years he established both clinical and laboratory research groups there, focusing on mucosal immune responses to pediatric conjugate vaccines and the pathogenesis of upper and lower respiratory tract pneumococcal infection. In 2001, he moved to Bristol where he is now Theme Leader for Infection and Immunity, University of Bristol, and Clinical Research Lead—Children, Genetics, Haematology, Reproductive Health and Childbirth for the NIHR Clinical Research Network: 638 About the Authors

West of England. He is also a senior clinician in the pediatric immunology and infectious diseases clinical service for Bristol Royal Hospital for Children and the South West region and heads the Bristol Children’s Vaccine Centre. In addition, he became Chairman of the WHO European Technical Advisory Group of Experts (ETAGE) on Immunization in December 2011 and ex ofﬁcio member of the WHO Strategic Advisory Group of Experts, and member of the UK Department of Health Joint Committee on Vaccination and Immunisation (JCVI) since October 2014. In 2015, he was elected president of the European Society for Paedia- tric Infectious Diseases (ESPID). His research interests are elucidation of the nature of naturally acquired mucosal immunity to pneumococcus, meningococcus, and other respiratory bacteria, the determinants of bacterial transmission and vaccine indirect effects, and development of tools to assess human immune responses to candidate vaccine antigens. He also leads and supports numerous clinical trials of drugs and med- icines in children.

Guillaume Fournier graduated in veterinary medicine in 2007 and obtained his PhD in veterinary sciences from the University of Liege (Belgium) in 2012. In 2013 he joined the Molecular Genet- ics of RNA Viruses Unit at Institut Pasteur (Paris, France) as a postdoctoral scientist. He used various approaches to study inﬂu- enza virus-host cell interactions involved in viral RNA synthesis and trafﬁcking. He is currently working at the Laboratoire National de Sante (LNS) of Luxembourg as a scientist in charge of developing diagnostic tests for emerging infectious diseases.

In 2013, Ana Rita Gonçalves obtained a PhD in life sciences from the University of Lausanne (Switzerland), where she was investigating the Lassa virus entry into human dendritic cells, and contributing to the development of a nanoparticle-based vaccine against arenaviruses under the supervision of Dr. Stefan Kunz. She joined the Swiss National reference Center for Influenza (Geneva Univer- sity Hospitals, Switzerland) in September 2014 to work on influenza seasonal epidemiology and surveillance. Her work is supported by the Swiss Federal office of Public Health. About the Authors 639

Urs F. Greber received his Msc and PhD degrees from ETH Zurich in experimental biology and biotechnology. He conducted postdoctoral studies in cell biology at the Scripps Research Institute in La Jolla, CA, USA, and in virus infection biology at Yale Medical School, New Haven, CT, USA. In 1995, he received a competitive junior group leader award from the Swiss National Science Foun- dation and was then promoted to assistant professor with tenure track at the University of Zurich (UZH) in Switzerland. After promotions to associate and full professor at UZH, he became an elected member of the European Molecular Biology Organization (EMBO), the Helen C. Levitt Visiting Professor at the Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA, and the Severo Ochoa lecturer in Madrid, Spain. Besides teaching biology and medical students at undergraduate and graduate levels at UZH and ETH Zurich, he has been teaching at the University of Utrecht, Madrid, Radboud, and the Pasteur Institute University of Hong Kong. He has given over 200 scientific oral presentations at conferences abroad, including keynote lectures, and trained more than 35 postdoctoral fellows and PhD students and about the same number of Msc students in his laboratory at UZH. He has been the scientific director of the UZH Msc program in virology, and the UZH Biology Undergraduate Summer School from 2012–2017, and organized seven international conferences. Dr. Greber is the president of the largest non-for-profit organization for Life Sciences in Switzerland (LS2). He is an elected member of the scientific advisory board of the European Society of Virology and the German Society of Virology (GfV). He is currently serving on the editorial boards of seven scientific journals, and on the boards of the French National Center for Scientific Research (CNRS), the French Agency for Research (ANR), and the German Research Foundation (DFG). Urs is an expert in virus infection biology, with pioneering contributions to virus-receptor interactions, virus entry and uncoating, membrane traffic, cytoplasmic transport, and DNA import into the nucleus. He published more than 100 peer- reviewed papers, many of them in major journals for broad audi- ence. His current research activities target human respiratory disease causing viruses, such as adenoviruses, rhinoviruses, and influenza viruses. He uses a combination of system-wide profiling analyses, reductionist studies of virus particles, cells and micro- tissue, and employs computational modeling to enhance mechanis- tic insights into infection biology. He is a co-founder of the biotech company 3-V Biosciences Inc., Menlo Park, CA, USA. 3-V Bios- ciences has research and discovery operations in antiviral and anti- cancer drugs with broad spectrum and low likelihood of resistance. 640 About the Authors

After receiving his bachelor’s degree from the University of Science and Technology of China in 2009, Long Gui joined Dr. Kelly Lee’s group as a graduate student at the University of Washington at Seattle. His PhD thesis focused on biophysical studies of influenza virus membrane fusion using fluorescence spectroscopy and cryo- electron tomography. He has defended his thesis titled “Structural Insights into Viral Membrane Fusion Machinery via Cryo-Electron Tomography: Influenza Virus and Human Parainfluenza Virus” in 2016 and currently he is working as a postdoctoral researcher at the University of Texas Southwestern Medical Center.

Johanneke D. Hemmink has a background in veterinary medicine and started her research career after working in clinical farm animal medicine. She conducted her MSc and PhD at the Roslin Institute in Edinburgh working on bovine immunology against the proto- zoan parasites Theileria annulata and Theileria parva. In 2014 she joined the swine inﬂuenza immunology group at the Pirbright Institute in Surrey to work on the swine inﬂuenza transmission dynamics project, linking transmission, evolutionary dynamics, pathogenesis, and immunity in pigs. The work is funded by the BBSRC.0

Esteban A. Hernandez-Vargas started working as a postdoctoral scientist and consequently as a group leader at the Helmholtz Centre for Infection Research (HZI) in Braunschweig, Germany. Since March 2017, he and his research group moved to the Frank- furt Institute for Advanced Studies. Furthermore, he was visiting scholar at Los Alamos National Laboratory (USA), Universidad de Guadalajara (Mexico), and lecturer at the Otto von Guericke Uni- versit€at Magdeburg, Germany. He is a research member of the Mexican Research Council (CONACYT) since 2013. He belongs to the Editorial Board of Infectious Diseases, a specialty of Fron- tiers in Medicine and Public Health.

Lorna Hodgson completed her PhD at the University of Bristol in 2014 in the laboratory of Professor Jeremy Tavare´. During her PhD, she used correlative light and electron microscopy (CLEM) to study the trafﬁcking of the glucose transporter, GLUT4. There- after, she moved to Professor Paul Verkade’s group at the Univer- sity of Bristol where she is now working as a postdoctoral researcher specializing in the development of CLEM techniques and their application to synthetic and cellular biology. About the Authors 641

Anja B. Hoffmann obtained her MSc in biomolecular sciences from Vrije Universiteit (Brussels, Belgium) in 2015. The same year, she has started her PhD project in the Lozach group where she investigates the entry of phleboviruses into cells.

Don Howard is the former director and a Fellow of the University of Notre Dame’s Reilly Center for Science, Technology, and Values, where he now functions as co-director of the center’s ethics of emerging technologies focus area. He holds a permanent appointment as a professor in the Department of Philosophy. With a ﬁrst degree in physics (BSc, Lyman Briggs College, Michi- gan State University, 1971), Howard went on to obtain both an MA (1973) and a PhD (1979) in philosophy from Boston Univer- sity, where he specialized in philosophy of physics under the direc- tion of Abner Shimony. A Fellow of the American Physical Society, Past Chair of APS’s Forum on the History of Physics, and current Chair of its Commit- tee on International Freedom of Scientists, Howard is an interna- tionally recognized expert on the history and philosophy of modern physics, especially the work of Einstein and Bohr. He served as assistant editor and contributing editor for The Collected Papers of Albert Einstein (Princeton University Press), and is co-editor of the Einstein Studies series (Springer). His video/ audio lecture series, Albert Einstein: Physicist, Philosopher, Human- itarian, is available from The Great Courses, and a collection of his essays on Einstein is in preparation for the University of Chicago Press. Howard is also the co-founder (1990) of the International Society for the History of Philosophy of Science and was the founding co-editor of its journal, HOPOS (University of Chicago Press). Howard has been writing and teaching about the ethics of science and technology for many years. Co-editor of the collection, The Challenge of the Social and the Pressure of Practice: Science and Values Revisited (University of Pittsburgh Press), Howard has led NSF-funded workshops on science and ethics at Notre Dame for physics REU students, is currently the lead PI on an NSF-EESE research ethics grant, and has taught courses on topics ranging from the moral choices of atomic scientists during World War II and the Cold War, to the ethics of emerging weapons technologies and robot ethics. He also serves as the Secretary of the International 642 About the Authors

Society for Military Ethics. Among his current research interests are ethical and legal issues in cyberconflict and cybersecurity as well as the ethics of autonomous systems. His paper, “Virtue in Cybercon- flict,” was published in 2014 in the volume, Ethics of Information Warfare (Springer), and his essay on “Civic Virtue and Cyberse- curity” will soon appear in the volume, The Nature of Peace and the Morality of Armed Conflict (Palgrave Macmillan). His editorials on technology ethics have appeared in the Wall Street Journal,on CNN,atInsideSources, and in other venues.

Edward C. Hutchinson started working on the molecular biology of inﬂuenza viruses as a graduate student with Paul Digard at the University of Cambridge. In 2009 he moved to the University of Oxford to do postdoctoral research work with Ervin Fodor, and in 2016 he set up a research group at the MRC-University of Glasgow Centre for Virus Research. His work on inﬂuenza virus molecular biology and proteomics is currently supported by the University of Glasgow and an MRC Career Development Award.

Michael J. Imperiale undertook his undergraduate and graduate education at Columbia University, receiving a BA and PhD in biological sciences. He then moved to the Rockefeller University, where he first became interested in viruses while studying gene regulation in the human pathogen, adenovirus. In 1984, Dr. Imperiale joined the Department of Microbiology and Immu- nology at the University of Michigan. He was promoted to associate professor in 1990 and to professor in 1996. He served as Interim Chair of the Department of Microbiology and Immunol- ogy (January, 2003–June, 2004), and is now Associate Chair. He is currently the Arthur F. Thurnau Professor of Microbiology and Immunology and is also the Director of the Doctoral Program in Cancer Biology. In 2009 Dr. Imperiale was awarded the Distin- guished Faculty Achievement Award from the University of Michi- gan. He was elected as a Fellow of the American Academy of Microbiology in 2010 and as a Fellow of the American Association for the Advancement of Science in 2011. In 2017, he was appointed as associate vice president for Research at the University of Michigan Dr. Imperiale’s research interests focus on the study of DNA tumor viruses. He has made important contributions to our understanding of how these viruses regulate expression of their genes, how they contribute to oncogenesis, and how they interact with the infected cell in order to cause acute disease. Most recently his laboratory has been examining the behavior of polyomaviruses in About the Authors 643 healthy individuals and immunosuppressed patients. Dr. Imperiale’s work has been funded by the NIH and other federal and private agencies and has been published in leading journals in the field. He has presented his findings at numerous national and international conferences and is founding editor-in-chief of mSphere and an editor of mBio. He has served on several NIH grant review panels, as well as National Research Council committees addressing the issues of responsible conduct of research, dual use life sciences research, and the intersection of science and security, and has published extensively on these topics. He served as an inaugural member of the National Science Advisory Board for Biosecurity from 2005 to 2014 and currently serves on the Committee on Science, Technology, and Law at the National Academies.

Yoshinori Ito started working on inﬂuenza virus associated encephalopathy as a graduate student at Nagoya University Gradu- ate School of Medicine. In 2000, he moved to the National Insti- tutes of Health (USA) to do postdoctoral research work, and in 2006 he set up a clinical/research group at Nagoya University Graduate School of Medicine. From Nagoya, Japan.

Lucas T. Jae was born on June 5, 1985, in Frankfurt, Germany. During his studies of human biology at the Philipps-University of Marburg, he spent time at the Karolinska Institute in Stockholm and the Whitehead Institute in Cambridge, the latter of which he returned to for his master’s thesis in the laboratory of Dr. Robert Weinberg. Subsequently, he moved to Amsterdam for his PhD in the laboratory of former Whitehead Fellow Dr. Thijn Brummelk- amp, with Dr. Rene´ Bernards as his co-advisor. After a short stint as a postdoc in the same group, he joined the Gene Center in Munich to establish his own laboratory.

Umut Karakus joined Prof. Silke Stertz’ group at the Institute of Medical Virology at the University of Zurich (Switzerland) in 2012 as a master’s student. After graduating, he was employed by a pharmaceutical company in the molecular diagnostics department. In 2014, he moved back to research and started a PhD in Prof. Silke Stertz’ group at the University of Zurich, where he is investigating the entry characteristics of the newly discovered bat inﬂuenza virus subtypes. 644 About the Authors

Erik A. Karlsson began his work on nutritional influences on influenza virus infection as a doctoral student in the laboratory of Dr. Melinda Beck in the Gilling’s School of Global Public Health at the University of North Carolina at Chapel Hill. In 2010, he went on to do postdoctoral work with Dr. Stacey Schultz-Cherry at St. Jude Children’s Research Hospital in Memphis, Tennessee, focusing further on nutrition in the context of influenza virology and pathogenesis as well as global influenza surveillance and risk assessment. In 2017, he moved to Institute Pasteur of Cambodia where he manages the National Influenza Center as well as the World Health Organization H5 Reference Laboratory and continues his work on nutritional influences on viral infection in the context of low- to middle-income countries.

Yoshihiro Kawaoka received his DVM from the Ministry of Agri- culture and Fishery in Japan, his PhD from Hokkaido University, Japan, and was trained in influenza virology by Dr. Robert Webster at St. Jude Children’s Research Hospital, Memphis, TN, USA. He is now a professor at the University of Wisconsin-Madison, Madi- son, WI, USA, and at the University of Tokyo, Japan. In Madison, he is the Director of the Influenza Research Institute which focuses on influenza, Ebola, and systems biology research. Dr. Kawaoka has made several critical contributions to influenza viruses, including: (1) Identification of a critical difference between avian influenza viruses that kill birds and those that do not (i.e., multibasic versus monobasic HA cleavage sequence); (2) Establishment of reverse genetics, which allows the generation of “designer” influenza viruses; (3) Characterization of pandemic 1918 virus and of highly pathogenic avian H5N1, H7N9 viruses including the identification of amino acids that are critical for the pathogenicity of these viruses; and (4) Isolation of a highly pathogenic H5N1 influenza virus that acquired the ability to transmit among ferrets via respiratory dro- plets. His major influenza virus research interests are to unravel the determinants of viral pathogenicity, to better understand influenza virus evolution, and to develop novel countermeasures to influenza virus infections.

Carolin Klemm began her research in the field of virology as a master’s student in the group of Friedemann Weber at the Univer- sity of Marburg. In 2012 she moved to Mu¨nster to work as a graduate student in the lab of Christina Ehrhardt. Since 2015 she continues her projects in the field of inflammatory processes during influenza virus and S. aureus super-infections as postdoc at the Institute of Virology. Her work is currently funded by the Univer- sity of Mu¨nster (IZKF-EhC2/006/15). About the Authors 645

Michael M. C. Lai is a long-time RNA virologist. His research career spans more than 40 years and covers various topics of retrovirus, coronavirus, and hepatitis D and C viruses. He spent most of his career at the University of Southern California School of Medi- cine, Los Angeles. In 2003, he moved to Academia Sinica, Taiwan, where he expanded his research interest to dengue virus and inﬂu- enza virus. Currently he is a distinguished professor and director of the Center for Emerging Viruses, China Medical University Hos- pital, Taiwan. Among his credit was an appointment as Howard Hughes Medical Institute Investigator. He received Presidential Science Medallion of Taiwan (2013) and Nikkei Asia Prize in Science and Technology (2017). He was a long-time editor of Virology.

Seema S. Lakdawala trained as a molecular virologist with Dr. Matthew Weitzman at the Salk Institute for Biological Studies in San Diego, CA, working on viral ubiquitin ligases and the host DNA damage response. In October of 2009, during the H1N1 pandemic, she began a postdoctoral fellowship with Dr. Kanta Subbarao at the National Institutes of Health (NIH) where she utilized her molecular virology expertise to study inﬂuenza virus assembly dynamics and airborne transmission. At the NIH, Seema collaborated with Dr. Hari Shroff, a microscopist, which sparked her interest in live cell imaging using light sheet microscopes. In the fall of 2015, Seema started an independent laboratory at the Uni- versity of Pittsburgh in the Microbiology and Molecular Genetics Department studying inﬂuenza virus assembly and pathogenesis. The University of Pittsburgh and an NIH early career award support her research. She is from Fort Worth, Texas.

Caroline Lanz joined the Institute of Medical Virology at the University of Zurich (Switzerland) in 2012 as a master’s student in Prof. Alexandra Trkola’s lab, where she studied the entry process of HIV-2 and SIV. For her PhD, she joined the lab of Prof. Silke Stertz at the same institute to study the human and swine IFITM- mediated restriction of inﬂuenza A virus. Since 2017, she is working as a postdoctoral researcher in Silke Stertz’ lab. 646 About the Authors

Kelly K. Lee received his AB in physics from Harvard University. His PhD work at the Johns Hopkins University in the lab of Bertrand Garcıá-Moreno E. focused on comparing quantitative experimental measures of electrostatic interactions in proteins with computational predictions. The significant role played by ionizable residues in protein function drew him to study pH-driven conformational changes in viruses as a postdoctoral fellow in Jack Johnson’s group at the Scripps Research Institute. While at Scripps, Dr. Lee received an NIH K99/R00 career inde- pendence award that supported his first studies of influenza virus using a set of complementary biophysical and structural approaches including cryo-EM, small-angle X-ray scattering, and structural mass spectrometry. His lab at the University of Washington, Seattle, now investigates the fusion proteins and entry processes of envel- oped viruses including influenza and HIV.

Valerie Le Sage trained as a molecular bacteriologist with Dr. Herve´ Le Moual at McGill University in Montreal, Que´bec, where she studied the two-component system PhoP/PhoQ in Salmonella typhimurium. In 2009, she started a postdoctoral fellowship in molecular virology with Dr. Bruce Banfield at Queen’s University in Kingston, Ontario. At Queen’s, Valerie conducted research efforts in the field of herpes virology that sought to exam- ine essential host and virus factors that promote infection. In 2012, she had the opportunity to drive multifaceted HIV-1 research in the laboratory of Dr. Andrew Mouland at Lady Davis Institute, Montreal, Que´bec, and examined the relationship between HIV-1 and several host factors, including the nuclear pore complex, mTOR, and the stress response. In the fall of 2016, Valerie joined the laboratory of Dr. Seema Lakdawala at the University of Pitts- burgh, to study influenza virus assembly and pathogenesis. She is from Montreal, Que´bec, Canada.

Psylvia Le´ger worked ﬁrst as a graduate student and then as a PhD student, with Dr. Miche`le Bouloy at the Institut Pasteur (Paris, France) where she got her PhD degree on the molecular biology of the highly pathogenic mosquito-borne bunyavirus Rift Valley Fever in 2009. In 2014, she joined the Lozach lab at the University Hospital Heidelberg as a postdoctoral fellow to pursue her work on arthropod-borne viruses. About the Authors 647

During his PhD with Vincent Croquette (Ecole Normale Super- ieure, Paris), Timothe´e Lionnet studied the mechanical properties of DNA and DNA unwinding enzymes using magnetic tweezers. He then went on to develop technologies to visualize transcription at the single molecule level in living cells, ﬁrst as a postdoc in the lab of Robert H. Singer (A. Einstein College of Medicine, NY) and then as Project Scientist coordinating the Transcription Imaging Consortium (HHMI Janelia Research Campus). Dr. Lionnet is currently assistant professor at the Institute for Systems Genetics (NYU School of Medicine) and his research group uses cutting- edge imaging technologies to interrogate gene expression mechanisms in living cells.

Marc Lipsitch is professor of epidemiology and director of the Center for Communicable Disease Dynamics at the Harvard School of Public Health. He is an author of more than 250 peer- reviewed publications on antimicrobial resistance, epidemiologic methods, mathematical modeling of infectious disease transmission, pathogen population genomics, and immunoepidemiology of Streptococcus pneumoniae. Recently he has had a growing interest in the use of transmission-dynamic simulations to improve the design of randomized and observational studies of infectious disease interventions. He has also begun to contribute to topics in bioethics related to infectious diseases and clinical trials in emer- gencies. Dr. Lipsitch joined the faculty of the Harvard School of Public Health in 1999, after a postdoctoral fellowship at Emory University with Dr. Bruce Levin, a visiting scientist appointment at CDC, and a DPhil in Zoology from the University of Oxford, where he studied with Drs. Robert May and Martin Nowak. He was a co-founder of the Cambridge Working Group in 2014, whose efforts helped to initiate a pause in US government funding for research involving the creation of potential pandemic pathogens, such as transmission-enhanced avian inﬂuenza strains. He has written extensively on aspects of science policy in relation to such studies. Dr. Lipsitch has received awards for research articles, mentoring, and journal reviewing. In 2015 he was elected a Fellow of the American Academy of Microbiology. He is or was on the editorial advisory boards/associate editor of eLife, PLoS Medicine, Journal of Infectious Diseases, American Journal of Epidemiology, Epidemiology, and Epidemics and has served as an advisor to CDC, FDA, PCAST, WHO, Congressional Budget Ofﬁce, Wellcome Trust, multiple pharmaceutical companies, and the Canadian and Mexican governments. 648 About the Authors

In 2008, Wen-Chun Liu started working on influenza viruses as a graduate student with Dr. Suh-Chin Wu at National Tsing-Hua University in Taiwan. Her thesis research focused on studies with influenza virus vaccines. In 2016, after graduation she became a recipient of a postdoc training fellowship from the Taiwan Ministry of Science and Technology, and transitioned to the Icahn school of Medicine at Mount Sinai in New York to receive mentored training by Dr. Randy A. Albrecht and Dr. Adolfo Garcıá-Sastre. Currently, her research is focused on studies on the immunology of and vaccines against influenza viruses and animal models of influenza.

Jason S. Long received his BSc in biology from University College London before going on to receive an MSc in virology from Impe- rial College London. He went on to achieve a PhD studying influenza virus as a joint project between Wendy Barclay at Imperial College London and the Animal and Plant Health Agency. He continued studying influenza virus with Wendy Barclay as a postdoctoral associate focusing on the host restriction of the influenza A virus polymerase. His research interests focus around virus-host interactions of emerging viruses and the mechanisms that underlie virus-host restriction.

Pierre-Yves Lozach obtained his PhD degree in virology at the Institut Pasteur (Paris, France) in 2004. He joined the lab of Ari Helenius (ETH Zurich, Switzerland) as a Marie-Curie postdoc fellow in 2007. He was appointed as tenure-track assistant professor at the INRS-Institut Armand Frappier (Canada) in 2011, and then granted a CellNetworks group leader position at the University Hospital Heidelberg (Germany) in 2013. His group investigates how arthropod-borne viruses infect humans and subsequently spread throughout the host, speciﬁcally from virology and cell biology perspectives.

Stephan Ludwig received his PhD from the University of Giessen, Germany. He moved to the University of Wu¨rzburg in 1994, Germany, and started to work as an assistant professor on the role of signal transduction pathways in inﬂammation and infection. In 2002 he was appointed associate professor for Molecular Medicine at the University of Du¨sseldorf, Germany, from where he ﬁnally moved to the University of Muenster in 2004 to take over the directorship of the Institute of Virology. His work is currently supported by several grants from the Deutsche Forschungsge- meinschaft (DFG), the Deutsche Krebshilfe, and the Federal Min- istry of Education and Research (BMBF). About the Authors 649

Taronna R. Maines is the Lead of the Pathogenesis Team in the Immunology and Pathogenesis Branch of CDC’s Inﬂuenza Divi- sion. Her research focuses on determining the risk to public health of emerging inﬂuenza viruses with pandemic potential and charac- terizing viral molecular determinants of virulence and transmission. She is a recipient of the Charles C. Shepard Award.

Patrick Matthias, PhD, is a senior group leader at the Friedrich Miescher Institute for Biomedical Research (FMI) in Basel, Swit- zerland. He is also adjunct professor at the University of Basel. He has a long-standing interest in the regulation of gene expression, in particular in the lymphoid system. During the last years a central focus of his laboratory has also been the study of protein acetylation and of histone deacetylases (HDACs). Work in the laboratory of Patrick Matthias has contributed importantly to understanding the role of speciﬁc HDACs, in particular HDAC1, 2, and 6, in normal and in pathological situations. Patrick Matthias is a member of the Faculty of 1000 and serves on several editorial and review boards. He is also the president of the Forum for Genetic Research, an organ of the Swiss Academy of Natural Sciences which fosters an interdisciplinary dialogue with political bodies and lay people on the impact of gene technology in our society.

Magalie Mazelier obtained her MSc in biotechnology at the Uni- versity of Marseille (France). In 2014, she joined the group of Pierre-Yves Lozach as a PhD student to study the host alternation of tick-borne bunyaviruses. 650 About the Authors

Be´ryl Mazel-Sanchez started working on influenza A virus as an undergraduate student with R. Volmer in Toulouse (France). In 2008, she moved to the University of St Andrews (Scotland) in the lab of R.M. Elliott. There she obtained a PhD working on bunyaviruses. In 2012, she went back to the influenza field as a postdoc in the group of P. Palese at Mount Sinai School of Medicine (New York, USA). Currently, Be´ryl is working on influenza A virus-host interaction as a postdoc in the recently established group of M. Schmolke at the University of Geneva (Switzerland).

Alice C. McHardy began working on computational methods for predicting the evolution of seasonal inﬂuenza viruses as a research staff member at the IBM T.J. Watson Research Center in Yorktown Heights, USA. She then became the head of “Computational Genomics and Epidemiology” group at the Max Planck Institute for Computer Science in Saarbru¨cken. In 2010 Alice McHardy became the chair of the Department for Algorithmic Bioinformat- ics at Heinrich Heine University in Du¨sseldorf. Since 2014 she is the head of the Computational Biology of Infection Research Group at the HZI.

Andrew Mehle began his career studying mouse mammary tumor virus as an undergraduate researcher at Villanova University. He continued his training in the Harvard PhD Program in Virology. There he studied under Dana Gabuzda, MD, to define the molecular mechanisms by which the HIV Vif protein counteracts the antiviral protein APOBEC3G. He continued to combine biochemistry and molecular virology during his postdoctoral research with Jennifer Doudna, PhD, at the University of California Berkeley. He set up the influenza virus system in the Doudna group—focusing on the viral polymerase—and dissected virus-host interactions that control influenza virus host range. He established his own research group at the University of Wisconsin-Madison in 2011, where he is currently an assistant professor. The lab maintains a focus on the viral replication machinery and how virus-host interactions govern the outcome of infection. Work in the Mehle Lab is funded by grants from the National Institutes of Health/National Institute for Allergy and Infectious Disease, the American Lung Association, the Greater Milwaukee Fund Shaw Scientist Award, and the UW2020 Initiative. He was recently named an Investigator in the Pathogenies of Infectious Disease by the Burroughs Wellcome Fund. About the Authors 651

Yasuyuki Miyake is a visiting scientist at the University of Bristol, UK. He is a JSPS (Japan Society for the Promotion of Science) Research Fellow at Nagoya University. The focus of Yasu’s research is to understand the protein function(s) which is related to human disease(s) by using various techniques such as biochemistry, cell biology, and structural biology. He received his PhD in medicine at Osaka University (2006), Master of Integrated Biosciences at the University of Tokyo (2002), and BSc at Shinshu University (2000). He has worked as a postdoctoral fellow at Kyoto university (2006–2010), a senior postdoctoral fellow in Friedrich Miescher Institute for Biomedical Research (FMI) in Basel (2010-2015), and a postdoctoral fellow at Shinshu University (2016–2017). Since 2018, he re-started his expertise as an RPD (re-start postdoctoral) research fellow at Nagoya University after his 4-month paternity leave. He was awarded a Pﬁzer Forschungspreis fu¨r Infektiologie, Rheumatologie und Immunologie (2016) together with Indranil Banerjee and Yohei Yamauchi. Yasu’s primary area of expertise is molecular biology. He aims to reveal the molecular mechanisms of ubiquitin functions in inﬂuenza virus virions and infected cells. He is also interested in the molecular architecture of the HDAC6- ubiquitin complex and the molecular structure of Ctc1-Stn1- Ten1 (CST) complex in DNA replication.

Nadia Naffakh obtained her PhD in virology from University Paris Diderot-Paris 7. She is a scientist at CNRS, the French National Research Council, and is leading a research group within the Molecular Genetics of RNA Viruses Unit at Institut Pasteur, Paris. She is studying molecular interactions between the inﬂuenza A virus transcriptional machinery and host cell components that are essential for the synthesis, processing, and trafﬁcking of the viral mRNAs and genomic RNAs. Her approaches include the development of original methods to document virus-host protein-protein interactions in an infectious context.

Gabriele Neumann received her PhD from Justus-Liebig Univer- sity, Giessen, Germany, for the demonstration that RNA polymerase I can be used to generate influenza viral RNAs. As a postdoctoral fellow in Dr. Kawaoka’s group, she developed an RNA polymerase I-based system for the artificial generation of influenza viruses (reverse genetics). She also developed a reverse genetics system for Ebola virus. After a stint in industry to work on the development of influenza vaccines, Dr. Neumann is now a research professor and distinguished scientist in Dr. Kawaoka’s group. She primarily focuses on determining the molecular basis of influenza virulence and pathogenicity, and on mimicking and eventually predicting the antigenic evolution of influenza viruses in order to improve influenza vaccines. 652 About the Authors

Van Kinh Nguyen taught epidemiology in Vietnam and studied statistics in Belgium. In 2014, he started working on modeling viral dynamics as a graduate student with Esteban A. Hernandez-Vargas at the Helmholtz Institute for Infection Research. He is currently working on multiscale modeling of infectious diseases at the Frank- furt Institute for Advanced Studies.

After studying mathematics at the University of Lu¨beck, Susanne Reimering began working on the evolution of inﬂuenza viruses in the Computational Biology of Infection Research Group led by Alice McHardy at the HZI in Braunschweig.

Cristina Risco is a group leader and head of the Cell Structure Laboratory at the National Center for Biotechnology, one of the institutes of the National Research Council of Spain. She obtained her PhD in biology from the Complutense University of Madrid, conducted postdoctoral research at the National Cancer Institute (NCI-FCRDC, NIH, MD, USA), and worked as a visiting scientist at the Max Plank Institute for Biochemistry (Martinsried, Ger- many), the Universite´ Pierre et Marie Curie, and the Institut Jac- ques Monod (Paris, France). Dr. Risco’s research makes use of current developments in imaging technology to study virus-host interactions.

Ine´s Romero-Brey started working on the molecular biology of aquatic birnaviruses as a graduate student with Carlos P. Dopazo in the Department of Microbiology and Parasitology, at the Univer- sity of Santiago de Compostela (Spain), directed by Alicia Este´vez Toranzo and Juan Luis Barja Pe´rez. Her PhD period included two research stays at the laboratories of James R. Winton (Western Fisheries Research Center, Seattle, USA) and of Vikram N. Vakharia (University of Maryland Biotechnology Institute, Maryland, USA). In 2008 she moved to the University of About the Authors 653

Heidelberg (Germany) to do postdoctoral research work with Ralf Bartenschlager. In Heidelberg Ine´s works on the visualization of virus-host interactions by means of high-resolution microscopy techniques, with a focus on the study of members of the family Flaviviridae. To this aim, she collaborates with staff members of the Electron Microscopy Core Facility (EMCF) at the European Molecular Biology Laboratory (EMBL, Heidelberg), where she has a visitor contract since 2008. Ine´s enjoys doing research and teaching at the University of Heidelberg, moved by one of her passions: understand the principles governing the cell architecture and how these nanomachines (viruses) remodel the cell landscape to perform a successful infection cycle.

Martin Sachse obtained his PhD at the University of Utrecht, the Netherlands, in 2003. After working as a postdoctoral fellow at the Institut Curie in Paris, he joined the electron microscopy core facility of the Institut Pasteur, Paris, France.

Andrea J. Sant is a professor of microbiology and immunology at the University of Rochester within the D.H. Smith Center for Vaccine Biology and Immunology. She was awarded her PhD in immunology from Washington University in St. Louis in immuno- genetics, and then completed a postdoctoral fellowship at the National Institutes of Health with Dr. Ronald Germain. She was a faculty member at the University of Chicago from 1985 to 2002 and after which she moved to Rochester. Her major interests throughout her career have been on MHC class II restricted anti- gen presentation and CD4 T cell recognition. In the past 12 years, she has become highly focused on the regulation of CD4 T cell responses to influenza vaccination and infection. She has been most intrigued by the functional heterogeneity in CD4 T cells specific for influenza, both in terms of mechanisms that underlie these pheno- types and the consequences of this heterogeneity in the host. Her laboratory studies this in both human and animal models of infection and vaccination.

Chandra Savage began her career with Charles River at a contract research laboratory in 2000 after obtaining a BS in toxicology from the University of Louisiana at Monroe. While managing a group of toxicology technicians for many years, she helped develop processes 654 About the Authors

and procedures for a wide variety of species and techniques. In 2008 she joined St. Jude Children’s Research Hospital where she currently manages a similar group of technologists. She provides researcher assistance for inﬂuenza models, toxicokinetic models, production colonies for severely immunocompromised research models, and surgery support.

Ivo F. Sbalzarini is professor of the Faculty of Computer Science of TU Dresden, where he holds the Chair of Scientiﬁc Computing for Systems Biology at the Center for Systems Biology Dresden (CSBD). At the same time, Ivo is also a tenured Senior Research Group Leader with the Max Planck Institute of Molecular Cell Biology and Genetics since June 2012, and a faculty member of the Department of Mathematics of TU Dresden since February 2016. He received his degree in mechanical engineering, with majors in control theory and computational science from ETH Zurich (Switzerland) in 2002, which was awarded the Willi Studer Prize. In 2006, he obtained his doctoral degree in computer science from ETH Zurich. His dissertation received the 2006 Chorafas Award from the Weizmann Institute of Science. From 2006 to 2012, he was assistant professor of computational science at ETH Zurich. Ivo is a life-long honorary member of the Technical Society of Zurich, an associate editor for BMC Bioinformatics, and serves on various conference, program, and reviewer boards. Since 2016, Ivo is the Vice Dean of the Faculty of Computer Science, and Spokes- person of the International Max Planck Research School for Cell, Developmental and Systems Biology (IMPRS-CellDevoSys). Since 2013, Ivo serves on the Steering and Executive Committees of the Center for Systems Biology Dresden (CSBD), and he is co-leader of the Biological Systems Path of the Center for Advancing Electron- ics Dresden (cfaed). His research interests include biological image analysis, computer simulation of biological processes, systems biology, and parallel high-performance computing.

Florian Ingo Schmidt did his first experiments with influenza as an undergraduate visiting student in the laboratory of George G. Brownlee at the University of Oxford. As a graduate student, he studied poxvirus entry with Ari Helenius at the ETH Zurich. In 2013, he moved to the Whitehead Institute/MIT, where he used alpaca nanobodies to study influenza virus and inflammasomes in the lab of Hidde L. Ploegh. In 2017 he established his own research group at the Institute of Innate Immunity at the University of Bonn, Germany. His current work on virus-induced inflammatory responses is supported by the Emmy Noether program of the German Research Foundation (DFG). From Bonn, Germany. About the Authors 655

Mirco Schmolke works on influenza A virus-host interactions using recombinant virus models since 2005, when he joined the group of Stephan Ludwig at the University of Mu¨nster, Germany, as a postdoc. Here he studied inflammatory responses of highly pathogenic avian influenza A virus infected primary human endo- thelial cells. From 2009 to 2014 he performed a second postdoc at the Icahn School of Medicine at Mount Sinai in New York, USA, in the group of Adolfo Garcıà Sastre, working on the role of accessory influenza A virus proteins in viral pathogenesis in animal models. Since 2014 he is assistant professor at the University of Geneva, Switzerland. Supported by the Swiss National fund, his team studies the impact of acute viral infections on host microbiota and the consequences of microbiota alteration for the host organism.

Holly A. Shelton has worked on the molecular biology of influenza viruses and utilized animal models for the virus since her first postdoctoral position with Professor Wendy Barclay in 2007. In 2011 she moved onto a Research Fellow’s program at the Pirbright Institute to initiate an independent group which culminated in her achieving group leader status in 2016. Along the way she has had two daughters. Holly’s current influenza research is supported by the BBSRC.

Monika Stegmann completed her PhD at the University of Oxford in 2015 working on a molecular immunology project with Neil Barclay, developing a label-free quantitative proteomics approach to investigate the role of labile disulﬁde bond cleavage during immune activation. Thereafter, she moved to the Advanced Proteomics Facility at the University of Oxford as a postdoctoral researcher and collaborated on various research projects. In 2017 she moved to UCB Pharma where she is now working in the cellular sciences department. From Switzerland, a village close to Zurich called Bonstetten. 656 About the Authors

Wen-Chi Su obtained her PhD from National Taiwan University studying gene regulation. She joined the laboratory of Dr. Michael M. C. Lai at Academia Sinica as a postdoctoral fellow and began her research on inﬂuenza virus in 2010. She joined China Medical University Hospital as an assistant researcher in 2012 and has been an assistant professor in China Medical University since 2014. Currently, her study focuses on virus-host interactions and viral pathogenesis.

Aartjan J. W. te Velthuis received his MSc in biochemistry and his PhD in medicine from the University of Leiden, the Netherlands, working on the replication of the SARS-coronavirus. He subsequently did his postdoctoral training in the laboratories of Ervin Fodor and Achilles Kapanidis at the University of Oxford. He is currently a Wellcome Trust Sir Henry Dale fellow and a Research Group Leader at the Department of Pathology, University of Cam- bridge. His research focuses on understanding the molecular mechanism of viral RNA-dependent RNA polymerases.

Terrence M. Tumpey is the chief of the Immunology and Patho- genesis Branch of CDC’s Influenza Division. His research in influenza virus pathogenesis and immunity has been recognized with the Lancet Award for the top scientific paper of 2005 and two Charles C. Shepard Awards for outstanding research paper at the CDC.

Andre van Kru¨chten first came in contact with the work on molecular mechanisms driven by secondary bacterial infection upon an influenza infection during his master’s program, which he finished in 2013 in the lab of Christina Ehrhardt. Since 2014 he works as a PhD student in her lab for more detailed studies on this topic. He was supported by a grant from the Ju¨rgen-Manchot Foundation and the Deutsche Forschungsgemeinschaft (SFB1009/B02). About the Authors 657

Paul Verkade obtained his PhD at the University of Utrecht, the Netherlands, in 1996. He did a postdoc at the EMBL, Heidelberg, in Germany after which he was asked to set up the Electron Micros- copy unit at the newly formed Max Planck Institute for Molecular Cell Biology in Dresden, Germany. In 2006 he moved to the University of Bristol, UK, where he set up the EM unit of the Wolfson Bioimaging Facility, a fully integrated light and electron microscopy center. His research group focuses on the development and application of microscopy techniques mainly for the study of sorting mechanisms in intracellular transport pathways. The main tools in the lab are electron microscopy (EM) and correlative light electron microscopy (CLEM) in which ﬁelds he has published over 70 papers. His lab is the home of the EMBO practical course on CLEM. The current focus of the lab is on the application of those techniques to the ﬁeld of synthetic biology, i.e., how are synthetic particles taken up and processed by cells.

Catherine J. Whittaker was awarded an International Fogarty Fellowship, which supported her postdoctoral training at the National Institutes of Health, USA. She returned to the UK to take up a post at the Institute for Animal Health to characterize avian antibody phage display platforms, and subsequently establish immune-speciﬁc chicken microarrays. In 2012 Catherine joined Public Health England where she now leads the translational inﬂu- enza group.

Yohei Yamauchi is the editor of this book. He began herpesvirus research as an undergraduate student at Nagoya University School of Medicine in the lab of Yukihiro Nishiyama. After graduating from med school with an eye to pursuing a scientific career, he first performed two years of clinical internship at the Japanese Red Cross Nagoya First Hospital. He then returned to the Nishiyama lab to do his PhD, and in 2008 graduated with a degree in Molec- ular Virology. Later in 2008 he was hired as an NIH-funded postdoc by Ari Helenius to work on the cell biology of influenza A virus entry at ETH Zu¨rich, Switzerland. He remained until the lab ceased operation in 2014 due to the retirement of Ari Helenius. The following year he moved to the University of Zu¨rich as O¨ berassistent. In 2016, he was recruited by the University of Bristol, UK, as Reader (associate professor) in Viral Cell Biology. Yohei’s research focus is understanding the mechanism of virus entry by combining virology, cell and molecular biology, high- throughput screening and imaging. From Aichi, Japan. The Yamauchi lab website can be found at yamauchilab.com. 658 About the Authors

Emilio Yańguëz obtained his PhD from the Universidad Autoń- oma de Madrid (Spain), under the supervision of Profs. Amelia Nieto and Juan Ortıń. During this time, he uncovered the mechanisms by which viral mRNAs are selectively translated in the cells infected with influenza A virus. In 2013, he joined the group of Prof. Silke Stertz at the University of Zurich (Switzerland), where he is currently working as a senior research associate. His main interest is the application of genome- and proteome-wide technologies for the discovery and characterization of new host-factors involved in influenza A virus replication. INDEX

A Catheter ...... 410, 413, 414, 419, 421, 423 Adenovirus...... 483, 611, 613, CD4 T cell ...... 514, 517, 617, 619, 625 523, 524, 526, 528 Aerosol...... v, 25, 53, 387–388, CD8 T cell ...... 514, 517, 523, 412, 421, 439 524, 526, 528, 532 Aerosol chamber ...... 411, 421 Cell biology ...... 221, 610, 617 Aggresome processing ...... 237 Cell lysis ...... 338, 364, 365, Allantoic ﬂuid ...... 67, 75, 89, 95, 372, 416, 445, 453 308, 312, 314, 315, 323 Chicken...... 6, 7, 11, 56, 60, Anesthesia ...... 409, 418–421, 423, 518 62, 63, 65–68, 72, 75, 83, 85, 89, 95, 98, 104, Animal models...... v, 401–429, 112, 113, 265, 307, 308, 312, 314, 323, 377, 432, 488–490, 513, 576, 579, 591, 603 401, 402, 404–406, 408–411, 413, 414, Antigenic escape...... 462, 466, 476, 417–420, 422, 423, 425, 427–429, 491, 495, 508 478–480, 485 Clathrin-mediated endocytosis...... 13 Antigenic evolution...... v, 462, 551–561 Clustered regularly interspaced short palindromic Antigenic selection...... 464, 466, 477, 478, 485 repeat (CRISPR)/Cas9...... 122, 139, 581 B Coding DNA (cDNA)...... 34, 45–47, 82, 83, 141, 156, 167, 191, 192, 331, 344, 352, Baculovirus ...... 336 353, 355, 356, 360, 463, 469, 470, 479, 483 Bioluminescence...... 432, 433, Co-infection ...... v, 611 436, 438–440, 456 Complementary RNA (cRNA)...... 13, 15, Biosafety ...... 34, 53, 62, 163, 33, 344–347, 352, 353, 355, 356, 360 192, 197, 215, 295, 305, 306, 313, 389, 412, Computational biology...... 553, 559 435–438, 444, 445, 448, 449, 451, 453, 455, Computational models 494, 501, 504, 521, 522, 526, 576, 577, discrete vs continuous models ...... 617, 618 580–582, 584, 585, 590, 593, 595–597 hypothesis-driven vs. data-driven models ..... 617, 619 Biosafety cabinet (BSC) ...... 34, 53, spatiotemporal vs. temporal models...... 617, 618 62, 192, 389–393, 395–397, 435–439, 441, 444, stochastic vs. deterministic models...... 617, 618 445, 448, 451, 453, 455, 492, 494, 501, 504, white box vs. black-box models...... 617, 618, 620 521, 522, 526 Computational software Biosafety level (BSL)...... 34, 62, AdaPatch 1.1 ...... 553 197, 215, 234, 283, 306, 312, 439, 441, 445, Antigenic Tree Inference 1.0...... 553 448, 581, 582, 596 AntiPatch 1.0 ...... 553 Biosecurity ...... 576, 577, 580, 590, 592, 593 FastTree 2.1...... 553 Blood sampling ...... 408–409, 417, 418 MUSCLE 3.8 ...... 553 Brain-heart infusion (BHI)...... 377, 378, 384 SweepDynamics 1.0 ...... 553 Bronchoalveolar lavage (BAL) ...... 29, 410, trimAl 1.2 ...... 553 415, 417, 419, 492, 499–501 Confocal microscopy ...... 163, 166, Bronchoscope...... 413 171, 173, 174, 180, 304 Bunyavirus ...... 613 Correlative light and electron microscopy (CLEM) ...... v, 164, 213–235, 237–259 C cRNP ...... 344 Cambridge Working Group ...... 593 Cryo-electron tomography Cap-snatching ...... 13, 15, 362, 370 (cryo-EM)...... 215, 261–278, 615, 619, 623 Cryosectioning ...... 239, 243, 248, 255, 281–299

Yohei Yamauchi (ed.), Influenza Virus: Methods and Protocols, Methods in Molecular Biology, vol. 1836, https://doi.org/10.1007/978-1-4939-8678-1, © Springer Science+Business Media, LLC, part of Springer Nature 2018 659 INFLUENZA VIRUS:METHODS AND PROTOCOLS 660 Index C-type lectins...... 161 F Cyberwarfare ...... 581 Cytokine ...... 15, 376, 514, Ferret ...... 6, 401–414, 417–419, 516, 517, 522–525, 529 422–424, 427–429, 432, 433, 435–439, 462, Cytopathic effect (CPE) ...... 29, 41, 476, 477, 480, 488–493, 499–502, 506–508, 42, 51, 55, 61, 70, 71, 73, 76, 77, 79, 85, 98, 112, 513–529, 576, 578–580, 590, 592, 599, 602 177, 178, 384, 385, 441, 477, 479, 483, 484 Fiducials ...... 221, 229, 241, 253, 258, 259, 267, 275 D Filter-aided sample preparation (FASP)...... 93–96, 98–105 Deep sequencing...... 122, 123, 125, 128, 559 First-strand synthesis...... 347, 355, 356 3D-electron microscopy (EM) methods ...... 213–235 Flow cytometry (FC) ...... 127, 133, Dengue virus (DV) ...... 122, 215 134, 150, 155, 160, 164, 167, 174–176, 489, Design centering ...... 622 493, 494, 504–506, 509, 514–516, 521, 522, Diagnosis ...... v, 5, 23–31, 41, 44, 524, 526, 528 62, 66, 86, 491, 572, 611 Fluorescence dequenching ...... 262, 263, Dual-view inverted selective-plane illumination 272, 274, 278 microscopy (diSPIM) ...... 305, 308, Fluorescence spectrometry ...... 262, 264 309, 315–321, 323, 324 Fluorescent labeling ...... 179 Dynamic light scattering...... 266, 271 Fluorimetry...... 160, 164, E 167, 174–175, 177, 181 Focused ion beam-scanning electron microscopy 50% Egg infectious dose (EID50) ...... 61, 65, (FIB-SEM)...... 214, 215, 75, 81, 428 222, 223, 229, 231–233 Electron tomography (ET)...... 196, 213, Freeze substitution (FS) ...... 214, 218, 214, 216, 217, 220, 221, 223, 225–227, 229, 219, 226, 227, 239, 241, 243, 247, 249, 254–256 230, 239, 262, 264, 267, 271, 273, 275, 419 G ELISpots...... 426, 489, 493, 501–504, 514, 516, 517, 522–525, 529 Gain of function (GOF) ...... v, 575–585, 589–604 Embedding ...... 214, 216–218, Gain of function research of concern 220, 222, 223, 225, 227, 229, 231–233, 239, (GoFRoC) ...... 590, 595–601 240, 242–244, 247, 249, 254, 282–285, 287, Genetic evolution...... 551–561 290–292, 296, 299, 520, 552 Gene-trap retrovirus ...... 122–124, 126 Embryonated chicken eggs ...... 6, 56, Genome-wide loss-of-function genetics ...... 121 62, 63, 65–68, 75, 83, 265, 307, 308, 312, 314, Globin RNA-primed transcription...... 350, 369–370 323, 508 Green fluorescent protein (GFP) ...... 228, Endocytosis ...... 13, 14, 238, 257, 304, 315, 318, 322, 345, 381, 385 142, 159–161, 164, 185–193, 237, 239, 253, Guinea pig ...... 401–406, 261, 331, 612, 620 408–411, 413, 414, 417–419, 422, 423, 484, 603 Endosome...... 13, 14, 155, 175, 185–187, 192, 193, 196, 237, 239, 253, H 254, 259, 261, 262, 282, 325, 612, 614, 621, 624 Enzyme-linked immunosorbent assay Haemadsorption (HAd) ...... 89, 91, 97, 98, 104, 113 (ELISA)...... 61, 75, HAP1 cells...... 122–124, 127, 128, 132–135 418, 435, 443, 445, 451, 488, 490, 491, Haploid human cells ...... 122 497–498, 502, 507, 524 Haploid screening ...... 121–135 Epidemics ...... 4, 8, 59, Hemagglutination assay (HA assay) ...... 29, 51, 61, 121, 303, 461, 462, 531, 551, 569–572, 575 64, 70–72, 75, 84, 85, 112, 113, 413, 422, 494 Escherichia coli ...... 37, 48, 56, Hemagglutination inhibition (HI) 143, 147, 156, 305, 333, 335–337, 464, 465, assay...... 477, 480, 484, 488, 470–473, 481, 482 491, 494–497, 552, 553, 555, 557, 559 Evans Blue Dye ...... 518–520 Hemagglutinin (HA) ...... 8, 61, 261, Evolution ...... 7, 14, 304, 462, 514, 533, 461, 487, 551, 578, 598 535, 543, 551–561, 600, 610, 618, 622, 623 Hemagglutinin stalk immunity ...... 488, 489 Hepatitis C virus (HCV) ...... 215, 228, 616 INFLUENZA VIRUS:METHODS AND PROTOCOLS Index 661 High efficiency particulate air (HEPA) filter ...... 402, 384, 435, 441, 444, 445, 448, 451, 455, 457, 406–408, 412, 516 465, 475, 477–479 High pathogenicity avian influenza viruses Mathematical modeling (HPAIV) ...... 576, 577, 579 Akaike information criteria (AIC)...... 538, 539, High-pressure freezing (HPF) ...... 214, 218, 545, 547 219, 226, 227, 229, 234, 239, 241, 243, 247, cost function...... 533, 536–538, 249, 256 541, 544, 546 High throughput sequencing (HTS)...... 36, 45, optimizer conditions...... 537, 538 53, 522 parameter boundaries ...... 537, 538, 544 Histone deacetylase 6 (HDAC6) ...... 330–337, parameter estimation ...... 531–545 339, 340 R...... 531–545 Human embryonic kidney (HEK) 293T MATLAB ...... 199, 205, 309, cells...... 123, 126, 127, 142, 319–321, 325 143, 148, 306, 310, 313, 322, 348, 349, 357, MaxQuant ...... 92, 94, 96, 97, 360, 362–364, 371, 464, 465, 473, 474, 482, 483 107–110, 113 Hybridization ...... 50, 196, 198, Medical Image Processing, Analysis and 199, 201–205, 208, 282, 318, 334, 341, 362, 463 Visualization (MIPAV)...... 309, 318–320, 324 Membrane fusion ...... 14, 159, 161, 163, I 175, 215, 261, 262, 264, 330 IgA-secreting B cells ...... 502, 504 Metal-tagging transmission electron microscopy ImageJ...... 168, 169, 223, (METTEM) ...... 281–299 Methicillin-resistant Staphylococcus aureus 232, 268, 272, 275, 309, 318 Imaris ...... 309, 318–320, 325 (MRSA)...... 375 Immunoglobulin response ...... 493 Microneutralisation (MN) assays ...... 552, 570 Microvesicles ...... 89 Immunogold ...... 281–299 Immunolabeling...... 239, 244, 251, Middle East respiratory syndrome coronavirus 252, 257, 258, 283, 285, 290, 292, 294–296, 299 (MERS-CoV)...... 577–579 Minigenome ...... 345, 348, 357, 600 In silico reconstitution ...... 615, 624 In situ polymerase assay...... 348–349, 359–362 Mouse ...... 12, 65, 299, 331, Interferon ...... 2, 68, 532, 552 377, 403–406, 408–411, 413, 414, 416, 418, Intracellular staining (ICS)...... 426, 505, 506, 516 419, 422, 423, 428, 433, 435–438, 449, 456, 488, 490, 516, 579 Intranasal challenge (IN)...... 411, 420, 428 Intratracheal challenge (IT)...... 421, 429 Mucosal atomization device (MAD)...... 411, 428 Intravenous pathogenicity index (IVPI).... 413, 422, 429 Multi-cycle infection ...... 376, 379, 385 Mutagenesis...... 38, 48, 50, L 122, 123, 127, 133–135, 305, 309, 322, 463, 464, 467–473, 479, 480, 485 Laryngoscope ...... 413, 419, 421 Lentivirus...... 139–158 N Light-sheet microscopy ...... v, 303–325 Nanobody...... 140 Lipophilic dye...... 163, 238, 265, 269 Liposome ...... 181, 261–278, 624 Nano-Glo...... 433, 435, 437, Liquid chromatography-tandem mass 439, 440, 442–445, 453, 456 NanoLuc spectrometry (LC-MS/MS) ...... 92, 93, ...... 432, 433, 439, 443, 445, 453, 455–457 96, 104, 330, 332 Live-cell imaging...... 163, 166, 171–174, Nasal wash ...... 25, 27, 28, 179, 180, 304, 309, 316, 619 410, 415, 417, 419, 424, 425, 429, 433 Natural challenge ...... 420, 428 M Nebulizer ...... 411, 428 Necropsy...... 414–415, 417, 499, 500, 508, 526 Macropinocytosis ...... 13 Neuraminidase (NA)...... 8, 11, 12, 15, 46, Madin Darby Canine Kidney (MDCK) cells...... 6, 26, 56, 107, 330, 450, 454, 551, 552, 602, 603 29, 35, 38–43, 50–53, 55, 60, 63, 64, 68–70, Next generation sequencing (NGS) ...... 62, 129, 73–76, 84, 98, 104, 110, 197, 203, 209, 241, 132, 142, 146, 151, 152, 154, 157, 158 297, 304, 307, 308, 310, 312, 314, 315, 320, Nuclear export protein (NEP) ...... 15, 107, 345 INFLUENZA VIRUS:METHODS AND PROTOCOLS 662 Index O RNA dependent RNA polymerase (RdRp) ...... 33, 161, 281, 343–346, 360, 362, 369, 371–373, 624 Orthomyxovirus...... 7, 13 RNA extraction ...... 25, 36, P 41–43, 53, 55, 82, 346, 352–353, 360, 371, 485 RNA imaging ...... v, 318 Pandemics...... v, 3, 4, 6, 8, 11, 16, 24, 60, RNA interference (RNAi) ...... 122, 611, 613, 614 68, 196, 303, 323, 431, 531, 551, 552, 557, 570, S 571, 575–585, 591, 596, 599–602, 604, 611 Particle tracking ...... 173, 174 Sanger sequencing...... 49, 53, 154, Passage ...... 12, 56, 69, 107, 322, 470, 472, 480 412, 419, 432, 439, 579, 590, 592 Sapphire discs ...... 214, 218–220, Peripheral blood mononuclear cells (PBMC) ...... 416, 226–229, 233, 256 426, 429, 492, 493, 499, 501, 508, 517, 518 Scientists for Science ...... 593 Phenotypic screen ...... 144, 149, 151–153 Sedation ...... 406–407, 411, Phosphorus assay...... 265, 266, 269, 271, 277 413, 414, 417, 421, 428 Plaque assay ...... 51, 52, 55, 61, 64, Sf9 cells ...... 332, 336, 338 68–71, 73–75, 112, 241, 242, 245, 307, 310, Sialic acid ...... 12–15, 66, 313, 315, 322, 415, 425, 426, 439, 465, 466, 68, 85, 261, 303, 427, 600, 602 475, 478 Silver enhancement (SE)...... 282, 284, Plaque purification ...... 39, 51–53 286–289, 297 Positive selection ...... 553, 554, 556, 560 Simulations ...... 532, 538, Potential pandemic pathogen (PPP)...... 575–585, 582, 584, 611, 615, 618–621, 623–625 590–597, 602, 603 Single domain antibody...... 139–158 Primer extension assay ...... 345, 361 Single molecule sensitivity RNA fluorescent in situ Proteomics...... v, 89–110 hybridisation (smFISH) ...... 195–207, 282 R Single-cycle infection ...... 376 Sodium dodecyl sulfate polyacrylamide gel Rab11 ...... 13, 15, 196, 215, 282 electrophoresis (SDS-PAGE)...... 91, 98, Radiolabelled capped oligonucleotide 112, 168, 169, 171, 178, 189, 191, 192, 272, transcription...... 349–351, 366–369 363, 366 Rapid influenza diagnostic tests (RIDTs)...... 23–26, Sourcing...... 403–406, 427 28, 29, 31 Spanish Flu ...... v Reassortment...... 11, 12, 196, Spinning disk confocal microscopy (SDCM) ...... 304 552, 554, 591, 592, 597 Spray factor (SF) ...... 392, 393, 396, 397 Receptor-destroying enzyme (RDE) ...... 436, Staphylococcus aureus (S. aureus) ...... 375–385 450, 453, 454, 466, 476, 477, 484, 491, 494, Subcellular fractionation...... 186, 187, 189–191, 193 495, 497 Super-infection ...... 375–385 Red blood cell (RBC) ...... 8, 61, Super-resolution microscopy...... 164 64, 65, 70–72, 83–85, 89, 95, 98, 104, 113, 416, Swab – nasopharyngeal...... 24, 27–29, 34, 40 426, 429, 466, 476, 484, 491, 492, 495, 497, Swine...... 4, 11, 196, 404–407, 499, 500, 507, 508, 515, 518, 519, 526 409–411, 413–415, 418, 419, 422, 423, 488, Replicon...... 345 552, 599 Reporter virus ...... 431–458 Swine influenza virus ...... 4, 6, 41, 60, 552 Respiratory pathogen...... 514 SYBR safe...... 306, 310 Reverse genetics (RG)...... v, 34, 47, System-wide analysis ...... 610 113, 196, 238, 297, 305–307, 309, 310, 312, T 322, 433, 462, 464, 482, 591, 592 Reverse transcriptase (RT)...... 30, 34, 37, Taxonomy...... 8, 107 45, 62, 66, 354 Tissue culture ...... 6, 60, 61, 63, Reverse transcription polymerase chain reaction 64, 68, 69, 73, 74, 98, 99, 122, 123, 127, 197, (RT-PCR) ...... 24, 25, 27–30, 290, 307, 308, 348, 349, 357, 390, 393, 402, 41, 43, 81–83, 86, 185–193, 353 435, 436, 441, 448, 450, 451, 453–455, 475, Revertant ...... 600 477, 478, 618, 621 INFLUENZA VIRUS:METHODS AND PROTOCOLS Index 663 50% Tissue culture infectious dose (TCID50)...... 61, Uukuniemi virus (UUKV) ...... 160–164, 166, 64, 65, 73, 75–80, 393, 396, 415, 425, 426, 433, 168–175, 178–180 435, 439, 441, 443, 445, 448–451, 453, 454, 458, 477, 484, 533, 542 V Titer ...... 413, 422, 534, 571 Vaccine trials...... v, 567–572 Tokuyasu...... 239, 240, Variable domain of heavy-chain only antibodies 242–244, 246–249, 253, 281–299 (VHHs)...... 140–143, 145–149, 151, 154–158 Total internal reflection fluorescence (TIRF) Viral ribonucleoproteins (vRNPs)...... 13, 185, microscopy...... 163, 167, 173, 174, 180 186, 193, 195–197, 281–299, 303–325, 330, 344 Transfection...... 34, 38, 51, 56, Virions ...... 7, 8, 10–16, 124, 126, 133, 148, 171, 223, 226, 228, 229, 89–110, 140, 141, 156, 163, 174, 178–180, 195, 306, 307, 310, 312, 313, 322, 334, 336, 349, 263, 322, 329–341, 506, 508, 509, 532, 552, 357–360, 362–364, 372, 465, 473, 474, 482, 483 609, 610, 612, 613, 616–619, 623–625 Transmissibility...... 431, 575, Virulence...... 376, 428, 578, 577–580, 590–592, 599, 600, 603 579, 582, 590, 592, 596, 600 Transmission electron microscopy (TEM) ...... 196, Virus entry...... v, 146, 159–181, 221, 229, 233, 239, 244, 253, 258, 259, 262, 186, 192, 237–259, 612, 616, 621, 623 267, 275, 281–299 Virus transport medium (VTM) ...... 402, 410, 415, 419 Transwell inserts...... 387, 388, Virus uncoating...... 186, 552 393, 394, 396 Virus-liposome contacts ...... 268, 275, 276 Tree inference...... 553, 555–557 Vitrification...... 267, 273, 275 Trizol extraction...... 352, 353 Turkey...... 7, 427, 484, 491, 495 W

U Western blotting (WB) ...... 90, 187–189, 191, 193, 266, 271, 272, 278, 332, 334, 335, 339 Ubiquitin ...... 113, 329–332, 339, 341 Wide-ﬁeld ﬂuorescence microscopy...... 171, 199 Ultramicrotomy ...... 216, 220, 229, 243, 244, 250, 284, 287, 298 X Unanchored ubiquitin ...... 330–332, 334, 335, 338, 339 Xenogen IVIS200 system ...... 433