Evolution and Adaptation of the Avian H7N9 Virus Into the Human Host
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Reverse Genetic Strategies to Interrogate Reassortment Restriction Among Group a Rotaviruses
REVERSE GENETIC STRATEGIES TO INTERROGATE REASSORTMENT RESTRICTION AMONG GROUP A ROTAVIRUSES BY JESSICA R. HALL A Thesis Submitted to the Graduate FACulty of WAKE FOREST UNIVERSITY GRADUATE SCHOOL OF ARTS AND SCIENCES in PArtiAl Fulfillment of the Requirements for the Degree of MASTER OF SCIENCE Biology August 2019 Winston-SAlem, North Carolina Approved By: SArah M. MCDonald, Ph.D., Advisor GloriA K. Muday, Ph.D., Chair DouglAs S. Lyles, Ph.D. JAmes B. PeAse, Ph.D. ACKNOWLEDGEMENTS This body of work wAs mAde possible by the influences of Countless people including, but not limited to, those named here. First, I Am thankful for my Advisor, Dr. SArah MCDonald, who paved wAy for this opportunity. Her infeCtious enthusiAsm for sCience served As A Consistent reminder to “keep getting baCk on the horse”. I Am grateful for my Committee members, Drs. DouglAs Lyles, GloriA Muday, And JAmes PeAse whose input And AdviCe Aided in my development into A CAreful sCientist who thinks CritiCAlly About her work. I Am Also thankful for Continued mentorship from my undergraduate reseArch advisor, Dr. NAthan Coussens, whose enthusiAsm for sCience inspired mine. I Am AppreCiAtive of All of my friends for their unyielding support. I Am blessed to have A solid foundation in my FAmily, both blood And Chosen. I Am thankful for my mother, LiAna HAll, who instilled in me my work ethiC And whose pride in me has inspired me to keep pursuing my dreAms. I Am forever indebted to Dr. DiAna Arnett, who has served As my personal And sCientifiC role model; thank you for believing in me, investing in me, And shaping me into the person and sCientist I am today. -
Key Factors That Enable the Pandemic Potential of RNA Viruses and Inter-Species Transmission: a Systematic Review
viruses Review Key Factors That Enable the Pandemic Potential of RNA Viruses and Inter-Species Transmission: A Systematic Review Santiago Alvarez-Munoz , Nicolas Upegui-Porras , Arlen P. Gomez and Gloria Ramirez-Nieto * Microbiology and Epidemiology Research Group, Facultad de Medicina Veterinaria y de Zootecnia, Universidad Nacional de Colombia, Bogotá 111321, Colombia; [email protected] (S.A.-M.); [email protected] (N.U.-P.); [email protected] (A.P.G.) * Correspondence: [email protected]; Tel.: +57-1-3-16-56-93 Abstract: Viruses play a primary role as etiological agents of pandemics worldwide. Although there has been progress in identifying the molecular features of both viruses and hosts, the extent of the impact these and other factors have that contribute to interspecies transmission and their relationship with the emergence of diseases are poorly understood. The objective of this review was to analyze the factors related to the characteristics inherent to RNA viruses accountable for pandemics in the last 20 years which facilitate infection, promote interspecies jump, and assist in the generation of zoonotic infections with pandemic potential. The search resulted in 48 research articles that met the inclusion criteria. Changes adopted by RNA viruses are influenced by environmental and host-related factors, which define their ability to adapt. Population density, host distribution, migration patterns, and the loss of natural habitats, among others, have been associated as factors in the virus–host interaction. This review also included a critical analysis of the Latin American context, considering its diverse and unique social, cultural, and biodiversity characteristics. The scarcity of scientific information is Citation: Alvarez-Munoz, S.; striking, thus, a call to local institutions and governments to invest more resources and efforts to the Upegui-Porras, N.; Gomez, A.P.; study of these factors in the region is key. -
Replication-Defective Chimeric Helper Proviruses and Factors Affecting Generation of Competent Virus
MOLECULAR AND CELLULAR BIOLOGY, May 1987, p. 1797-1806 Vol. 7, No. 5 0270-7306/87/051797-10$02.00/0 Copyright © 1987, American Society for Microbiology Replication-Defective Chimeric Helper Proviruses and Factors Affecting Generation of Competent Virus: Expression of Moloney Murine Leukemia Virus Structural Genes via the Metallothionein Promoter ROBERT A. BOSSELMAN,* ROU-YIN HSU, JOAN BRUSZEWSKI, SYLVIA HU, FRANK MARTIN, AND MARGERY NICOLSON Amgen, Thousand Oaks, California 91320 Received 15 October 1986/Accepted 28 January 1987 Two chimeric helper proviruses were derived from the provirus of the ecotropic Moloney murine leukemia virus by replacing the 5' long terminal repeat and adjacent proviral sequences with the mouse metallothionein I promoter. One of these chimeric proviruses was designed to express the gag-pol genes of the virus, whereas the other was designed to express only the env gene. When transfected into NIH 3T3 cells, these helper proviruses failed to generate competent virus but did express Zn2 -inducible trans-acting viral functions needed to assemble infectious vectors. One helper cell line (clone 32) supported vector assembly at levels comparable to those supported by the Psi-2 and PA317 cell lines transfected with the same vector. Defective proviruses which carry the neomycin phosphotransferase gene and which lack overlapping sequence homology with the 5' end of the chimeric helper proviruses could be transfected into the helper cell line without generation of replication-competent virus. Mass cultures of transfected helper cells produced titers of about 104 G418r CFU/ml, whereas individual clones produced titers between 0 and 2.6 x 104 CFU/ml. -
Technical Glossary
WBVGL 6/28/03 12:00 AM Page 409 Technical Glossary abortive infection: Infection of a cell where there is no net increase in the production of infectious virus. abortive transformation: See transitory (transient or abortive) transformation. acid blob activator: A regulatory protein that acts in trans to alter gene expression and whose activity depends on a region of an amino acid sequence containing acidic or phosphorylated residues. acquired immune deficiency syndrome (AIDS): A disease characterized by loss of cell-mediated and humoral immunity as the result of infection with human immunodeficiency virus (HIV). acute infection: An infection marked by a sudden onset of detectable symptoms usually followed by complete or apparent recovery. adaptive immunity (acquired immunity): See immunity. adjuvant: Something added to a drug to increase the effectiveness of that drug. With respect to the immune system, an adjuvant increases the response of the system to a particular antigen. agnogene: A region of a genome that contains an open reading frame of unknown function; origi- nally used to describe a 67- to 71-amino acid product from the late region of SV40. AIDS: See acquired immune deficiency syndrome. aliquot: One of a number of replicate samples of known size. a-TIF: The alpha trans-inducing factor protein of HSV; a structural (virion) protein that functions as an acid blob transcriptional activator. Its specificity requires interaction with certain host cel- lular proteins (such as Oct1) that bind to immediate-early promoter enhancers. ambisense genome: An RNA genome that contains sequence information in both the positive and negative senses. The S genomic segment of the Arenaviridae and of certain genera of the Bunyaviridae have this characteristic. -
Dissecting Human Antibody Responses Against Influenza a Viruses and Antigenic Changes That Facilitate Immune Escape
University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2018 Dissecting Human Antibody Responses Against Influenza A Viruses And Antigenic Changes That Facilitate Immune Escape Seth J. Zost University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Allergy and Immunology Commons, Immunology and Infectious Disease Commons, Medical Immunology Commons, and the Virology Commons Recommended Citation Zost, Seth J., "Dissecting Human Antibody Responses Against Influenza A Viruses And Antigenic Changes That Facilitate Immune Escape" (2018). Publicly Accessible Penn Dissertations. 3211. https://repository.upenn.edu/edissertations/3211 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/3211 For more information, please contact [email protected]. Dissecting Human Antibody Responses Against Influenza A Viruses And Antigenic Changes That Facilitate Immune Escape Abstract Influenza A viruses pose a serious threat to public health, and seasonal circulation of influenza viruses causes substantial morbidity and mortality. Influenza viruses continuously acquire substitutions in the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). These substitutions prevent the binding of pre-existing antibodies, allowing the virus to escape population immunity in a process known as antigenic drift. Due to antigenic drift, individuals can be repeatedly infected by antigenically distinct influenza strains over the course of their life. Antigenic drift undermines the effectiveness of our seasonal influenza accinesv and our vaccine strains must be updated on an annual basis due to antigenic changes. In order to understand antigenic drift it is essential to know the sites of antibody binding as well as the substitutions that facilitate viral escape from immunity. -
Current and Novel Approaches in Influenza Management
Review Current and Novel Approaches in Influenza Management Erasmus Kotey 1,2,3 , Deimante Lukosaityte 4,5, Osbourne Quaye 1,2 , William Ampofo 3 , Gordon Awandare 1,2 and Munir Iqbal 4,* 1 West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Legon, Accra P.O. Box LG 54, Ghana; [email protected] (E.K.); [email protected] (O.Q.); [email protected] (G.A.) 2 Department of Biochemistry, Cell & Molecular Biology, University of Ghana, Legon, Accra P.O. Box LG 54, Ghana 3 Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Accra P.O. Box LG 581, Ghana; [email protected] 4 The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, UK; [email protected] 5 The University of Edinburgh, Edinburgh, Scotland EH25 9RG, UK * Correspondence: [email protected] Received: 20 May 2019; Accepted: 17 June 2019; Published: 18 June 2019 Abstract: Influenza is a disease that poses a significant health burden worldwide. Vaccination is the best way to prevent influenza virus infections. However, conventional vaccines are only effective for a short period of time due to the propensity of influenza viruses to undergo antigenic drift and antigenic shift. The efficacy of these vaccines is uncertain from year-to-year due to potential mismatch between the circulating viruses and vaccine strains, and mutations arising due to egg adaptation. Subsequently, the inability to store these vaccines long-term and vaccine shortages are challenges that need to be overcome. Conventional vaccines also have variable efficacies for certain populations, including the young, old, and immunocompromised. -
Adenoviral Vector-Based Vaccine Platforms for Developing the Next Generation of Influenza Vaccines
Review Adenoviral Vector-Based Vaccine Platforms for Developing the Next Generation of Influenza Vaccines Ekramy E. Sayedahmed 1 , Ahmed Elkashif 1, Marwa Alhashimi 1, Suryaprakash Sambhara 2,* and Suresh K. Mittal 1,* 1 Department of Comparative Pathobiology, Purdue Institute for Immunology, Inflammation and Infectious Disease, Purdue University Center for Cancer Research, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA; [email protected] (E.E.S.); [email protected] (A.E.); [email protected] (M.A.) 2 Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA * Correspondence: [email protected] (S.S.); [email protected] (S.K.M.) Received: 2 August 2020; Accepted: 17 September 2020; Published: 1 October 2020 Abstract: Ever since the discovery of vaccines, many deadly diseases have been contained worldwide, ultimately culminating in the eradication of smallpox and polio, which represented significant medical achievements in human health. However, this does not account for the threat influenza poses on public health. The currently licensed seasonal influenza vaccines primarily confer excellent strain-specific protection. In addition to the seasonal influenza viruses, the emergence and spread of avian influenza pandemic viruses such as H5N1, H7N9, H7N7, and H9N2 to humans have highlighted the urgent need to adopt a new global preparedness for an influenza pandemic. It is vital to explore new strategies for the development of effective vaccines for pandemic and seasonal influenza viruses. The new vaccine approaches should provide durable and broad protection with the capability of large-scale vaccine production within a short time. The adenoviral (Ad) vector-based vaccine platform offers a robust egg-independent production system for manufacturing large numbers of influenza vaccines inexpensively in a short timeframe. -
Through a Combination of Continual Antigenic Drift of Surface Proteins and High Transmission Rates the Identity of Circulating I
Title: Computer-assisted vaccine design Hao Zhou, Ramdas S. Pophale, and Michael W. Deem Departments of Bioengineering and Physics & Astronomy Rice University Houston, TX, USA Abstract We define a new parameter to quantify the antigenic distance between two H3N2 influenza strains: we use this parameter to measure antigenic distance between circulating H3N2 strains and the closest vaccine component of the influenza vaccine. For the data between 1971 and 2004, the measure of antigenic distance correlates better with efficacy in humans of the H3N2 influenza A annual vaccine than do current state of the art measures of antigenic distance such as phylogenetic sequence analysis or ferret antisera inhibition assays. We suggest that this measure of antigenic distance could be used to guide the design of the annual flu vaccine. We combine the measure of antigenic distance with a multiple-strain avian influenza transmission model to study the threat of simultaneous introduction of multiple avian influenza strains. For H3N2 influenza, the model is validated against observed viral fixation rates and epidemic progression rates from the World Health Organization FluNet – Global Influenza Surveillance Network. We find that a multiple-component avian influenza vaccine is helpful to control a simultaneous multiple introduction of bird-flu strains. We introduce Population at Risk (PaR) to quantify the risk of a flu pandemic, and calculate by this metric the improvement that a multiple vaccine offers. Computer-assisted vaccine design Introduction Circulating influenza virus uses the ability to change its surface proteins, along with its high transmission rate, to flummox the adaptive immune response of the host. The random accumulation of mutations in the hemagglutinin (HA) and neuraminidase (NA) epitopes, the regions on surface of the viral proteins that are recognized by host antibodies, pose a formidable challenge to the design of an effective annual flu vaccine. -
Detection of Influenza a Viruses from Environmental Lake and Pond Ice
TITLE “DETECTION OF INFLUENZA A VIRUSES FROM ENVIRONMENTAL LAKE AND POND ICE” Zeynep A. Koçer A Dissertation Submitted to the Graduate College of Bowling Green State University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY August 2010 Committee: Scott O. Rogers, Advisor W. Robert Midden Graduate Faculty Representative John Castello George Bullerjahn Paul Morris ii ABSTRACT Scott O. Rogers, Advisor Environmental ice is an ideal matrix for the long-term protection of organisms due to the limitation of degradative processes. As a result of global climate change, some glaciers and polar ice fields are melting at rapid rates. This process releases viable microorganisms that have been embedded in the ice, sometimes for millions of years. We propose that viral pathogens have adapted to being entrapped in ice, such that they are capable of infecting naïve hosts after melting from the ice. Temporal gene flow, which has been termed genome recycling (Rogers et al., 2004), may allow pathogens to infect large host populations rapidly. Accordingly, we hypothesize that viable influenza A virions are preserved in lake and pond ice. Our main objective was to identify influenza A (H1-H16) from the ice of a few lakes and ponds in Ohio that have high numbers of migratory and local waterfowl visiting the sites. We developed a set of hemagglutinin subtype-specific primers for use in four multiplex RT-PCR reactions. Model studies were developed by seeding environmental lake water samples in vitro with influenza A viruses and subjecting the seeded water to five freeze-thaw cycles at -20oC and -80oC. -
Antigenic Variation in Vector-Borne Pathogens
Synopsis Antigenic Variation in Vector-Borne Pathogens Alan G. Barbour* and Blanca I. Restrepo† *University of California Irvine, Irvine, California; and †Corporación para Investigaciones Biológicas, Medellín, Colombia Several pathogens of humans and domestic animals depend on hematophagous arthropods to transmit them from one vertebrate reservoir host to another and maintain them in an environment. These pathogens use antigenic variation to prolong their circulation in the blood and thus increase the likelihood of transmission. By convergent evolution, bacterial and protozoal vector-borne pathogens have acquired similar genetic mechanisms for successful antigenic variation. Borrelia spp. and Anaplasma marginale (among bacteria) and African trypanosomes, Plasmodium falciparum, and Babesia bovis (among parasites) are examples of pathogens using these mechanisms. Antigenic variation poses a challenge in the development of vaccines against vector- borne pathogens. What Is Antigenic Variation? original antigen is archived in the cell and can be Immunodominant antigens are commonly used in the future. The adaptive immune system used to distinguish strains of a species of of an infected vertebrate selects against the pathogens. These antigens can vary from strain original infecting serotype, but that specific to strain to the extent that the strain-specific response is ineffective against new variants. One immune responses of vertebrate reservoirs example of antigenic variation occurs in determine the population structure of the B. hermsii, a cause of tickborne relapsing fever pathogen. One such strain-defining antigen is (4), which has a protein homologous to the OspC the OspC outer membrane protein of the Lyme protein of B. burgdorferi. However, instead of a disease spirochete Borrelia burgdorferi in the single version of this gene, each cell of B. -
Origins and Evolution of the Global RNA Virome
bioRxiv preprint doi: https://doi.org/10.1101/451740; this version posted October 24, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Origins and Evolution of the Global RNA Virome 2 Yuri I. Wolfa, Darius Kazlauskasb,c, Jaime Iranzoa, Adriana Lucía-Sanza,d, Jens H. 3 Kuhne, Mart Krupovicc, Valerian V. Doljaf,#, Eugene V. Koonina 4 aNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA 5 b Vilniaus universitetas biotechnologijos institutas, Vilnius, Lithuania 6 c Département de Microbiologie, Institut Pasteur, Paris, France 7 dCentro Nacional de Biotecnología, Madrid, Spain 8 eIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious 9 Diseases, National Institutes of Health, Frederick, Maryland, USA 10 fDepartment of Botany and Plant Pathology, Oregon State University, Corvallis, Oregon, USA 11 12 #Address correspondence to Valerian V. Dolja, [email protected] 13 14 Running title: Global RNA Virome 15 16 KEYWORDS 17 virus evolution, RNA virome, RNA-dependent RNA polymerase, phylogenomics, horizontal 18 virus transfer, virus classification, virus taxonomy 1 bioRxiv preprint doi: https://doi.org/10.1101/451740; this version posted October 24, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 19 ABSTRACT 20 Viruses with RNA genomes dominate the eukaryotic virome, reaching enormous diversity in 21 animals and plants. The recent advances of metaviromics prompted us to perform a detailed 22 phylogenomic reconstruction of the evolution of the dramatically expanded global RNA virome. -
Viruses Affecting Tropical and Subtropical Crops: Biology, 1 Diversity, Management
Viruses Affecting Tropical and Subtropical Crops: Biology, 1 Diversity, Management Gustavo Fermin,1* Jeanmarie Verchot,2 Abdolbaset Azizi3 and Paula Tennant4 1Instituto Jardín Botánico de Mérida, Faculty of Sciences, Universidad de Los Andes, Mérida, Venezuela; 2Department of Entomology and Plant Pathology, Oklahoma State University, Stillwater, Oklahoma, USA; 3Department of Plant Pathology, Faculty of Agriculture, Tarbiat Modares University, Tehran, Iran; 4Department of Life Sciences, The University of the West Indies, Mona Campus, Jamaica 1.1 Introduction of various basic concepts and phenomena in biology (Pumplin and Voinnet, 2013; Scholthof, Viruses are the most abundant biological en- 2014). However, they have also long been tities throughout marine and terrestrial eco- considered as disease-causing entities and systems. They interact with all life forms, are regarded as major causes of considerable including archaea, bacteria and eukaryotic losses in food crop production. Pathogenic organisms and are present in natural or agri- viruses imperil food security by decimating cultural ecosystems, essentially wherever life crop harvests as well as reducing the quality forms can be found (Roossinck, 2010). The of produce, thereby lowering profitability. concept of a virus challenges the way we de- This is particularly so in the tropics and fine life, especially since the recent discover- subtropics where there are ideal conditions ies of viruses that possess ribosomal genes. throughout the year for the perpetuation of These discoveries include the surprisingly the pathogens along with their vectors. Vir- large viruses of the Mimiviridae (Claverie and uses account for almost half of the emerging Abergel, 2012; Yutin et al., 2013), the Pan- infectious plant diseases (Anderson et al., doraviruses that lack phylogenetic affinity 2004).