DOCSLIB.ORG

Bats Are a Major Natural Reservoir for Hepaciviruses and Pegiviruses

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Bats Are a Major Natural Reservoir for Hepaciviruses and Pegiviruses Bats are a major natural reservoir for hepaciviruses and pegiviruses Phenix-Lan Quana,1, Cadhla Firtha, Juliette M. Contea, Simon H. Williamsa, Carlos M. Zambrana-Torreliob, Simon J. Anthonya,b, James A. Ellisonc, Amy T. Gilbertc, Ivan V. Kuzminc,2, Michael Niezgodac, Modupe O. V. Osinubic, Sergio Recuencoc, Wanda Markotterd, Robert F. Breimane, Lems Kalembaf, Jean Malekanif, Kim A. Lindbladeg, Melinda K. Rostalb, Rafael Ojeda-Floresh, Gerardo Suzanh, Lora B. Davisi, Dianna M. Blauj, Albert B. Ogunkoyak, Danilo A. Alvarez Castillol, David Moranl, Sali Ngamm, Dudu Akaiben, Bernard Agwandao, Thomas Briesea, Jonathan H. Epsteinb, Peter Daszakb, Charles E. Rupprechtc,3, Edward C. Holmesp, and W. Ian Lipkina aCenter for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032; bEcoHealth Alliance, New York, NY 10001; cPoxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333; dDepartment of Microbiology and Plant Pathology, University of Pretoria, Pretoria 0002, South Africa; eCenters for Disease Control and Prevention in Kenya, Nairobi, Kenya; fUniversity of Kinshasa, Kinshasa 11, Democratic Republic of the Congo; gCenters for Disease Control and Prevention Guatemala, 01015, Guatemala City, Guatemala; hFacultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510 México D. F., Mexico; iCenters for Disease Control and Prevention Nigeria, Abuja, Nigeria; jInfectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333; kDepartment of Veterinary Medicine, Ahmadu Bello University, Samaru, Zaria, Kaduna State, Nigeria; lCenter for Health Studies, Universidad del Valle de Guatemala, 01015, Guatemala City, Guatemala; mLaboratoire National Vétérinaire, B.P. 503 Garoua, Cameroon; nCentre de Surveillance de la Biodiversité, University of Kisangani, B.P. 2012 Kisangani, Democratic Republic of the Congo; oMammalogy Section, National Museums of Kenya, 00100 Nairobi, Kenya; pSydney Emerging Infections and Biosecurity Institute, School of Biological Sciences and Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia Edited* by Harvey Alter, National Institutes of Health, Bethesda, MD, and approved March 25, 2013 (received for review February 19, 2013) Although there are over 1,150 bat species worldwide, the diversity cause of chronic liver disease, cirrhosis, and hepatocellular carci- of viruses harbored by bats has only recently come into focus as noma, with ∼3% of the global population infected (16, 17). HCV a result of expanded wildlife surveillance. Such surveys are of and its distant relative, GB virus B (GBV-B), belong to the genus importance in determining the potential for novel viruses to emerge Hepacivirus within the family Flaviridae of single-stranded, positive- in humans, and for optimal management of bats and their habitats. sense RNA viruses (18, 19). New World monkeys can be experi- To enhance our knowledge of the viral diversity present in bats, we mentally infected with GBV-B, resulting in clinical hepatitis (20). initially surveyed 415 sera from African and Central American bats. Recently, nonprimate hepaciviruses (NPHV) were discovered in Unbiased high-throughput sequencing revealed the presence of domestic animals (dogs, horses), expanding the natural host range a highly diverse group of bat-derived viruses related to hepacivi- of these agents (21–23). A new flavivirus genus, Pegivirus, has been ruses and pegiviruses within the family Flaviridae. Subsequent PCR proposed for GB viruses GBV-A, GBV-C, and GBV-D (19). GBV-A screening of 1,258 bat specimens collected worldwide indicated the viruses have been identified in nonhuman primates and are not presence of these viruses also in North America and Asia. A total of known to infect humans, whereas GBV-C is frequently isolated 83 bat-derived viruses were identified, representing an infection from humans and chimpanzees (19). GBV-D was recently identi- rate of nearly 5%. Evolutionary analyses revealed that all known fied in Old World frugivorous bats (24). No pegiviruses have yet hepaciviruses and pegiviruses, including those previously docu- been identified to cause disease in their hosts (19). mented in humans and other primates, fall within the phylogenetic Here, we report the discovery of a highly diverse group of bat- diversity of the bat-derived viruses described here. The prevalence, derivedvirusesrelatedtohepaciviruses and pegiviruses. The unprecedented viral biodiversity, phylogenetic divergence, and prevalence, unprecedented viral biodiversity, and broad geo- worldwide distribution of the bat-derived viruses suggest that bats graphic distribution of these viruses, identified throughout the are a major and ancient natural reservoir for both hepaciviruses and order Chiroptera, suggest that bats are a key natural reservoir for pegiviruses and provide insights into the evolutionary history of both hepaciviruses and pegiviruses. hepatitis C virus and the human GB viruses. Results etermining the natural reservoirs for emerging pathogens is Discovery of Bat-Derived Hepaciviruses and Pegiviruses. We surveyed Dcritical for disease prediction and prevention. Nearly 60% of serum specimens from 415 apparently healthy bats captured emerging infectious diseases in humans are zoonotic, with up to from five different countries (Guatemala, Cameroon, Nigeria, 70% originating from wildlife (1). Bats [order Chiroptera, sub- orders Yinpterochiroptera and Yangochiroptera (2, 3)] are a nat- ural reservoir for many important zoonotic viruses that cause severe Author contributions: P.-L.Q. and W.I.L. designed research; P.-L.Q., J.M.C., and S.H.W. per- disease in humans, including lyssaviruses, severe acute respiratory formed research; P.-L.Q., C.M.Z.-T., S.J.A., J.A.E., A.T.G., I.V.K., M.N., M.O.V.O., S.R., W.M., R.F.B., L.K., J.M., K.A.L., M.K.R., R.O.-F., G.S., L.B.D., D.M.B., A.B.O., D.A.A.C., D.M., S.N., syndrome (SARS)-related coronaviruses (SARS-related CoV), D.A., B.A., J.H.E., P.D., and C.E.R. contributed new reagents/analytic tools; P.-L.Q., C.F., J.M.C., filoviruses, henipaviruses, and other paramyxoviruses (4–13). In S.H.W., C.M.Z.-T., T.B., E.C.H., and W.I.L. analyzed data; and P.-L.Q., C.F., T.B., E.C.H., and addition, several viruses establish persistent viral infections in bats, W.I.L. wrote the paper. in which apparent clinical signs appear only rarely (5). Bats possess The authors declare no conflict of interest. unique characteristics that may contribute to their capacity to *This Direct Submission article had a prearranged editor. function as a major reservoir host for viruses, including long life- Data deposition: The sequences reported in this paper have been deposited in the span, high species diversity, unique immune systems, gregarious GenBank database. For a list of accession numbers for the viruses identified in this study, roosting behaviors, and high spatial mobility and population see SI Appendix, Tables S6 and S7. densities (5). 1To whom correspondence should be addressed. E-mail: [email protected]. Although hepatitis C virus (HCV) was discovered more than 20 y 2Present address: Aravan, LLC, Lilburn, GA 30047. ago, its origin is unknown, and, until recently, humans appeared to 3Present address: The Global Alliance for Rabies Control, Manhattan, KS 66502. be its only natural host (14, 15). HCV was initially isolated from the This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. serum of a person with non-A, non-B hepatitis and is now a leading 1073/pnas.1303037110/-/DCSupplemental. 8194–8199 | PNAS | May 14, 2013 | vol. 110 | no. 20 www.pnas.org/cgi/doi/10.1073/pnas.1303037110 Downloaded by guest on September 25, 2021 Democratic Republic of the Congo, and Kenya) that represent 33 genetic material from a total of 58 bat-derived viruses was species, 26 genera, and seven families (SI Appendix, Tables S1 and detected (SI Appendix, Tables S3 and S4). S2). Aliquots of sera were combined into 43 pools for nucleic acid To further explore the distribution of these viruses in other extraction; total RNA was randomly amplified and subjected to countries and bat species, an additional 1,166 sera/plasma speci- unbiased high-throughput sequencing (UHTS) (25). After re- mens and 83 tissue specimens from 34 bats (kidney, liver, and lung), moval of host sequences, each pool yielded between 87 and 3,098 representing 40 species, 31 genera, and seven families of bats from unique reads and 1–128 assembled contiguous sequences. The Nigeria, Bangladesh, and Mexico were screened (SI Appendix,Table analysis of these sequence data at the nucleotide (nt) and amino S2). Twenty-three sera/plasma and one lung specimen were posi- tive. Additional specimens from 9 of the bats from Mexico with acid (aa) levels revealed the presence of sequences with distant positive sera specimens, consisting of seven oral and two rectal similarity to flaviviruses in 29 sera pools. Between 1 and 716 fla- swabs were also tested. One positive rectal swab was detected (SI vivirus sequences, ranging from 50 to 10,803 nt in length, were fi Appendix,TablesS3andS4). identi ed in the positive pools. The sequences showed aa sequence In total, 1,673 specimens, collected between 2007 and 2011 from similarities ranging from 24% to 100% to members of the genus 1,615 bats representing 58 species, 44 genera, and eight families in Hepacivirus or Pegivirus. Specific and degenerate primers targeting seven countries worldwide were screened (SI Appendix,TableS2). a conserved motif in the RNA-dependent RNA polymerase gene The genetic material of bat-derived viruses was detected in six of (RdRp or NS5B) were designed from the UHTS data and used to the eight families of bats tested, representing all major phyloge- confirm the initial findings, and further for screening all individual netic lineages of the chiroptera.
Load more

Recommended publications
  • Antiviral Bioactive Compounds of Mushrooms and Their Antiviral Mechanisms: a Review
    viruses Review Antiviral Bioactive Compounds of Mushrooms and Their Antiviral Mechanisms: A Review Dong Joo Seo 1 and Changsun Choi 2,* 1 Department of Food Science and Nutrition, College of Health and Welfare and Education, Gwangju University 277 Hyodeok-ro, Nam-gu, Gwangju 61743, Korea; [email protected] 2 Department of Food and Nutrition, School of Food Science and Technology, College of Biotechnology and Natural Resources, Chung-Ang University, 4726 Seodongdaero, Daeduck-myun, Anseong-si, Gyeonggi-do 17546, Korea * Correspondence: [email protected]; Tel.: +82-31-670-4589; Fax: +82-31-676-8741 Abstract: Mushrooms are used in their natural form as a food supplement and food additive. In addition, several bioactive compounds beneficial for human health have been derived from mushrooms. Among them, polysaccharides, carbohydrate-binding protein, peptides, proteins, enzymes, polyphenols, triterpenes, triterpenoids, and several other compounds exert antiviral activity against DNA and RNA viruses. Their antiviral targets were mostly virus entry, viral genome replication, viral proteins, and cellular proteins and influenced immune modulation, which was evaluated through pre-, simultaneous-, co-, and post-treatment in vitro and in vivo studies. In particular, they treated and relieved the viral diseases caused by herpes simplex virus, influenza virus, and human immunodeficiency virus (HIV). Some mushroom compounds that act against HIV, influenza A virus, and hepatitis C virus showed antiviral effects comparable to those of antiviral drugs. Therefore, bioactive compounds from mushrooms could be candidates for treating viral infections. Citation: Seo, D.J.; Choi, C. Antiviral Bioactive Compounds of Mushrooms Keywords: mushroom; bioactive compound; virus; infection; antiviral mechanism and Their Antiviral Mechanisms: A Review.
    [Show full text]
  • COVID-19: Perspective, Patterns and Evolving Strategies
    COVID-19: Perspective, Patterns and Evolving strategies Subject Category: Clinical Virology Vinod Nikhra* Department of Medicine, Hindu Rao Hospital & NDMC Medical College, New Delhi, India Submitted: 02 June 2020 | Approved: 06 July 2020 | Published: 09 July 2020 Copyright: © 2020 Nikhra V. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. DOI: https://dx.doi.org/10.29328/ebook1003 ORCID: https://orcid.org/0000-0003-0859-5232 *Corresponding author: Dr. Vinod Nikhra, M.D. Consultant and Faculty, Department of Medicine, Hindu Rao Hospital & NDMC Medical College, New Delhi, India, Tel: 91-9810874937; Email: [email protected]; drvinodnikhra@rediff mail.com Open Access COVID-19: Perspective, Patterns and Evolving strategies Table of Contents - 7 Chapters Sl No Chapters Title Pages The Trans-Zoonotic Virome Interface: Measures to 1 Chapter 1 003-011 Balance, Control and Treat Epidemics Exploring Pathophysiology of COVID-19 Infection: Faux 2 Chapter 2 012-020 Espoir and Dormant Therapeutic Options The Agent and Host Factors in COVID-19: Exploring 3 Chapter 3 021-036 Pathogenesis and Therapeutic Implications Adverse Outcomes for Elderly in COVID-19: Annihilation 4 Chapter 4 037-047 of the Longevity Dream Identifying Patterns in COVID-19: Morbidity, Recovery, 5 Chapter 5 048-058 and the Aftermath The New Revelations: Little-known Facts about COVID-19 6 Chapter 6 059-068 and their Implications Fear, Reaction and Rational Behaviour to COVID-19 in 7 Chapter 7 069-076 Public, Health Professionals and Policy Planners La Confusion: Caring for COVID-19 patients 8 Postscript 077-079 and the raging, engulfi ng and debilitating pandemic 9 Acknowledgement 080-080 *Corresponding HTTPS://WWW.HEIGHPUBS.ORG author: Dr.
    [Show full text]
  • Assembling Evidence for Identifying Reservoirs of Infection
    TREE-1806; No. of Pages 10 Review Assembling evidence for identifying reservoirs of infection 1 1,2 1,3 1 4 Mafalda Viana , Rebecca Mancy , Roman Biek , Sarah Cleaveland , Paul C. Cross , 3,5 1 James O. Lloyd-Smith , and Daniel T. Haydon 1 Boyd Orr Centre for Population and Ecosystem Health, Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK 2 School of Computing Science, University of Glasgow, Glasgow G12 8QQ, UK 3 Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA 4 US Geological Survey, Northern Rocky Mountain Science Center 2327, University Way, Suite 2, Bozeman, MT 59715, USA 5 Department of Ecology and Evolutionary Biology, University of California at Los Angeles, Los Angeles, CA 90095, USA Many pathogens persist in multihost systems, making patterns of incidence and prevalence (see Glossary) that the identification of infection reservoirs crucial for result from the connectivity between source and target devising effective interventions. Here, we present a con- populations (black arrows in Figure I in Box 1). We then ceptual framework for classifying patterns of incidence review methods that allow us to identify maintenance or and prevalence, and review recent scientific advances nonmaintenance populations (squares or circles in Figure that allow us to study and manage reservoirs simulta- I, Box 1), how they are connected (arrows in Figure I, Box neously. We argue that interventions can have a crucial 1), and the role that each of these populations has in role in enriching our mechanistic understanding of how maintaining the pathogen (i.e., reservoir capacity).
    [Show full text]
  • Variation in Antimicrobial Susceptibility Among Borrelia Burgdorferi Strains? Emir Hodzic*
    BOSNIAN JOURNAL OF BASIC MEDICAL SCIENCES REVIEW WWW.BJBMS.ORG Lyme Borreliosis: is there a preexisting (natural) variation in antimicrobial susceptibility among Borrelia burgdorferi strains? Emir Hodzic* Real-Time PCR Research and Diagnostic Core Facility, School of Veterinary Medicine, University of California at Davis, California, United States of America ABSTRACT The development of antibiotics changed the world of medicine and has saved countless human and animal lives. Bacterial resistance/tolerance to antibiotics have spread silently across the world and has emerged as a major public health concern. The recent emergence of pan-resistant bacteria can overcome virtually any antibiotic and poses a major problem for their successful control. Selection for antibiotic resistance may take place where an antibiotic is present: in the skin, gut, and other tissues of humans and animals and in the environment. Borrelia burgdorferi, the etiological agents of Lyme borreliosis, evades host immunity and establishes persistent infections in its mammalian hosts. The persistent infection poses a challenge to the effective antibiotic treatment, as demonstrated in various animal models. An increasingly heterogeneous sub- population of replicatively attenuated spirochetes arises following treatment, and these persistent antimicrobial tolerant/resistant spirochetes are non-cultivable. The non-cultivable spirochetes resurge in multiple tissues at 12 months after treatment, withB. burgdorferi-specific DNA copy levels nearly equivalent to those found in shame-treated experimental animals. These attenuated spirochetes remain viable, but divide slowly, thereby being tolerant to antibiotics. Despite the continued non-cultivable state, RNA transcription of multiple B. burgdorferi genes was detected in host tissues, spirochetes were acquired by xenodiagnostic ticks, and spirochetal forms could be visualized within ticks and mouse tissues.
    [Show full text]
  • Hepatitis C Virus P7—A Viroporin Crucial for Virus Assembly and an Emerging Target for Antiviral Therapy
    Viruses 2010, 2, 2078-2095; doi:10.3390/v2092078 OPEN ACCESS viruses ISSN 1999-4915 www.mdpi.com/journal/viruses Review Hepatitis C Virus P7—A Viroporin Crucial for Virus Assembly and an Emerging Target for Antiviral Therapy Eike Steinmann and Thomas Pietschmann * TWINCORE †, Division of Experimental Virology, Centre for Experimental and Clinical Infection Research, Feodor-Lynen-Str. 7, 30625 Hannover, Germany; E-Mail: [email protected] † TWINCORE is a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI). * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +49-511-220027-130; Fax: +49-511-220027-139. Received: 22 July 2010; in revised form: 2 September 2010 / Accepted: 6 September 2010 / Published: 27 September 2010 Abstract: The hepatitis C virus (HCV), a hepatotropic plus-strand RNA virus of the family Flaviviridae, encodes a set of 10 viral proteins. These viral factors act in concert with host proteins to mediate virus entry, and to coordinate RNA replication and virus production. Recent evidence has highlighted the complexity of HCV assembly, which not only involves viral structural proteins but also relies on host factors important for lipoprotein synthesis, and a number of viral assembly co-factors. The latter include the integral membrane protein p7, which oligomerizes and forms cation-selective pores. Based on these properties, p7 was included into the family of viroporins comprising viral proteins from multiple virus families which share the ability to manipulate membrane permeability for ions and to facilitate virus production. Although the precise mechanism as to how p7 and its ion channel function contributes to virus production is still elusive, recent structural and functional studies have revealed a number of intriguing new facets that should guide future efforts to dissect the role and function of p7 in the viral replication cycle.
    [Show full text]
  • Impact of Babesia Microti Infection on the Initiation and Course Of
    Tołkacz et al. Parasites Vectors (2021) 14:132 https://doi.org/10.1186/s13071-021-04638-0 Parasites & Vectors RESEARCH Open Access Impact of Babesia microti infection on the initiation and course of pregnancy in BALB/c mice Katarzyna Tołkacz1,2*, Anna Rodo3, Agnieszka Wdowiarska4, Anna Bajer1† and Małgorzata Bednarska5† Abstract Background: Protozoa in the genus Babesia are transmitted to humans through tick bites and cause babesiosis, a malaria-like illness. Vertical transmission of Babesia spp. has been reported in mammals; however, the exact timing and mechanisms involved are not currently known. The aims of this study were to evaluate the success of vertical transmission of B. microti in female mice infected before pregnancy (mated during the acute or chronic phases of Babesia infection) and that of pregnant mice infected during early and advanced pregnancy; to evaluate the pos- sible infuence of pregnancy on the course of parasite infections (parasitaemia); and to assess pathological changes induced by parasitic infection. Methods: The frst set of experiments involved two groups of female mice infected with B. microti before mating, and inseminated on the 7th day and after the 40th day post infection. A second set of experiments involved female mice infected with B. microti during pregnancy, on the 4th and 12th days of pregnancy. Blood smears and PCR targeting the 559 bp 18S rRNA gene fragment were used for the detection of B. microti. Pathology was assessed histologically. Results: Successful development of pregnancy was recorded only in females mated during the chronic phase of infection. The success of vertical transmission of B.
    [Show full text]
  • MODELING the SPREAD of the 1918 INFLUENZA PANDEMIC in a NEWFOUNDLAND COMMUNITY a Dissertation Presented to the Faculty of the Gr
    MODELING THE SPREAD OF THE 1918 INFLUENZA PANDEMIC IN A NEWFOUNDLAND COMMUNITY A Dissertation presented to the Faculty of the Graduate School at the University of Missouri In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy By JESSICA LEA DIMKA Dr. Lisa Sattenspiel, Dissertation Supervisor MAY 2015 The undersigned, appointed by the dean of the Graduate School, have examined the dissertation entitled MODELING THE SPREAD OF THE 1918 INFLUENZA PANDEMIC IN A NEWFOUNDLAND COMMUNITY Presented by Jessica Lea Dimka A candidate for the degree of Doctor of Philosophy And hereby certify that, in their opinion, it is worthy of acceptance. Professor Lisa Sattenspiel Professor Gregory Blomquist Professor Mary Shenk Professor Enid Schatz ACKNOWLEDGEMENTS This research could not have been completed without the support and guidance of many people who deserve recognition. Dr. Lisa Sattenspiel provided the largest amount of assistance and insight into this project, from initial development through model creation and data analysis to the composition of this manuscript. She has been an excellent mentor over the last seven years. I would also like to extend my gratitude to my committee members – Dr. Greg Blomquist, Dr. Mary Shenk, and Dr. Enid Schatz – for their advice, comments, patience and time. I also would like to thank Dr. Craig Palmer for his insight and support on this project. Additionally, I am grateful to Dr. Allison Kabel, who has provided me with valuable experience, advice and support in my research and education activities while at MU. Many thanks go to the librarians and staff of the Provincial Archives of Newfoundland and Labrador and the Centre for Newfoundland Studies at Memorial University of Newfoundland.
    [Show full text]
  • Natural Recombination of Equine Hepacivirus Subtype 1 Within The
    Virology 533 (2019) 93–98 Contents lists available at ScienceDirect Virology journal homepage: www.elsevier.com/locate/virology Natural recombination of equine hepacivirus subtype 1 within the NS5A and T NS5B genes ∗ Gang Lua,b,c,1, Jiajun Oua,b,c,1, Yankuo Suna,1, Liyan Wua,b,c, Haibin Xua,b,c, Guihong Zhanga, , ∗∗ Shoujun Lia,b,c, a College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, People's Republic of China b Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical Animal Diseases, Guangzhou, Guangdong Province, People's Republic of China c Guangdong Technological Engineering Research Center for Pet, Guangzhou, Guangdong Province, People's Republic of China ARTICLE INFO ABSTRACT Keywords: Equine hepacivirus (EqHV) was first reported in 2012 and is the closest known homolog of hepatitis Cvirus Equine hepacivirus (HCV). A number of studies have reported HCV recombination events. The aim of this study was to determine Subtype whether recombination events occur in EqHV strains. Considering that no information on the Chinese EqHV Recombination event genome sequence is available, we first sequenced the near-complete genomes of three field EqHV strains. Intra-subtype Through systemic analysis, we obtained strong evidence supporting a recombination event within the NS5A and China NS5B genes in the American EqHV strains, but not in the strains from China or other countries. Finally, using cut- off values for determination of HCV genotypes and subtypes, we classified the EqHV strains fromaroundthe world into one unique genotype and three subtypes. The recombination event occurred in subtype 1 EqHV strains. This study provides critical insights into the genetic variability and evolution of EqHV.
    [Show full text]
  • Prediction and Prevention of the Next Pandemic Zoonosis
    Series Zoonoses 3 Prediction and prevention of the next pandemic zoonosis Stephen S Morse, Jonna A K Mazet, Mark Woolhouse, Colin R Parrish, Dennis Carroll, William B Karesh, Carlos Zambrana-Torrelio, W Ian Lipkin, Peter Daszak Lancet 2012; 380: 1956–65 Most pandemics—eg, HIV/AIDS, severe acute respiratory syndrome, pandemic infl uenza—originate in animals, See Comment pages 1883 are caused by viruses, and are driven to emerge by ecological, behavioural, or socioeconomic changes. Despite their and 1884 substantial eff ects on global public health and growing understanding of the process by which they emerge, no This is the third in a Series of pandemic has been predicted before infecting human beings. We review what is known about the pathogens that three papers about zoonoses emerge, the hosts that they originate in, and the factors that drive their emergence. We discuss challenges to their Mailman School of Public control and new eff orts to predict pandemics, target surveillance to the most crucial interfaces, and identify Health (Prof S S Morse PhD), and Center for Infection and prevention strategies. New mathematical modelling, diagnostic, communications, and informatics technologies can Immunity (Prof W I Lipkin MD); identify and report hitherto unknown microbes in other species, and thus new risk assessment approaches are Columbia University, needed to identify microbes most likely to cause human disease. We lay out a series of research and surveillance New York, NY, USA; One Health opportunities and goals that could help to overcome these challenges and move the global pandemic strategy from Institute, School of Veterinary Medicine, University of response to pre-emption.
    [Show full text]
  • Sero-Monitoring of Horses Demonstrates the Equivac® Hev Hendra Virus Vaccine to Be Highly Effective in Inducing Neu-Tralising A
    Article Sero-Monitoring of Horses Demonstrates the Equivac® HeV Hendra Virus Vaccine to Be Highly Effective in Inducing Neutralising Antibody Titres Kim Halpin * , Kerryne Graham and Peter A. Durr Australian Centre for Disease Preparedness (ACDP), Commonwealth Scientific and Industrial Research Organisation (CSIRO), 5 Portarlington Road, East Geelong, VIC 3219, Australia; [email protected] (K.G.); [email protected] (P.A.D.) * Correspondence: [email protected]; Tel.: +61-352275510 Abstract: Hendra virus (HeV) is a high consequence zoonotic pathogen found in Australia. The HeV vaccine was developed for use in horses and provides a One Health solution to the prevention of human disease. By protecting horses from infection, the vaccine indirectly protects humans as well, as horses are the only known source of infection for humans. The sub-unit-based vaccine, containing recombinant HeV soluble G (sG) glycoprotein, was released by Pfizer Animal Health (now Zoetis) for use in Australia at the end of 2012. The purpose of this study was to collate post-vaccination serum neutralising antibody titres as a way of assessing how the vaccine has been performing in the field. Serum neutralization tests (SNTs) were performed on serum samples from vaccinated horses submitted to the laboratory by veterinarians. The SNT results have been analysed, together with age, dates of vaccinations, date of sampling and location. Results from 332 horses formed the data Citation: Halpin, K.; Graham, K.; set. Provided horses received at least three vaccinations (consisting of two doses 3–6 weeks apart, Durr, P.A. Sero-Monitoring of Horses and a third dose six months later), horses had high neutralising titres (median titre for three or more Demonstrates the Equivac® HeV vaccinations was 2048), and none tested negative.
    [Show full text]
  • Proline to Threonine Mutation at Position 162 of NS5B of Classical
    viruses Article Proline to Threonine Mutation at Position 162 of NS5B of Classical Swine Fever Virus Vaccine C Strain Promoted Genome Replication and Infectious Virus Production by Facilitating Initiation of RNA Synthesis Huining Pang, Ling Li, Hongru Liu and Zishu Pan * State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China; [email protected] (H.P.); [email protected] (L.L.); [email protected] (H.L.) * Correspondence: [email protected] Abstract: The 30untranslated region (30UTR) and NS5B of classical swine fever virus (CSFV) play vital roles in viral genome replication. In this study, two chimeric viruses, vC/SM30UTR and vC/b30UTR, with 30UTR substitution of CSFV Shimen strain or bovine viral diarrhea virus (BVDV) NADL strain, were constructed based on the infectious cDNA clone of CSFV vaccine C strain, respectively. After virus rescue, each recombinant chimeric virus was subjected to continuous passages in PK-15 cells. The representative passaged viruses were characterized and sequenced. Serial passages resulted in generation of mutations and the passaged viruses exhibited significantly increased genomic replication efficiency and infectious virus production compared to parent viruses. A proline to threonine mutation at position 162 of NS5B was identified in both passaged vC/SM30UTR 0 Citation: Pang, H.; Li, L.; Liu, H.; and vC/b3 UTR. We generated P162T mutants of two chimeras using the reverse genetics system, 0 0 Pan, Z. Proline to Threonine Mutation separately. The single P162T mutation in NS5B of vC/SM3 UTR or vC/b3 UTR played a key role in at Position 162 of NS5B of Classical increased viral genome replication and infectious virus production.
    [Show full text]
  • Mechanism for Coordinated RNA Packaging and Genome Replication by Rotavirus Polymerase VP1
    Structure Article Mechanism for Coordinated RNA Packaging and Genome Replication by Rotavirus Polymerase VP1 Xiaohui Lu,1,5 Sarah M. McDonald,2 M. Alejandra Tortorici,2,6 Yizhi Jane Tao,1,7 Rodrigo Vasquez-Del Carpio,2,8 Max L. Nibert,3 John T. Patton,2 and Stephen C. Harrison1,4,* 1Laboratory of Molecular Medicine, Children’s Hospital and Harvard Medical School, Boston, MA 02115, USA 2Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA 3Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA 4Howard Hughes Medical Institute, Children’s Hospital, Boston, MA 02115, USA 5Present address: Optimal Decisions Group, Cambridge, MA 02142, USA 6Present address: Unite´ de Virologie Structurale, De´ partement de Virologie, Institut Pasteur, 75724 Paris Cedex 15, France 7Present address: Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77251, USA 8Present address: Department of Molecular Physiology and Biophysics, Mount Sinai School of Medicine, New York, NY 10029, USA *Correspondence: [email protected] DOI 10.1016/j.str.2008.09.006 SUMMARY reflect this particle-associated RNA synthesis mechanism (Butcher et al., 2001; Tao et al., 2002). Rotavirus RNA-dependent RNA polymerase VP1 cat- Rotaviruses, members of the Reoviridae family, are nonenvel- alyzes RNA synthesis within a subviral particle. This oped particles with three concentric protein layers surrounding activity depends on core shell protein VP2. A con- 11 segments of dsRNA (Estes and Kapikian, 2007; Prasad served sequence at the 30 end of plus-strand RNA et al., 1996). The outermost layer is shed during cell entry, result- templates is important for polymerase association ing in a transcriptionally active, double-layered particle (DLP).
    [Show full text]