Bats are a major natural reservoir for hepaciviruses and pegiviruses

Although there are over 1,150 bat species worldwide, the diversity of viruses harbored by bats has only recently come into focus as a result of expanded wildlife surveillance. Such surveys are of importance in determining the potential for novel viruses to emerge in humans, and for optimal management of bats and their habitats. To enhance our knowledge of the viral diversity present in bats, we initially surveyed 415 sera from African and Central American bats. Unbiased high-throughput sequencing revealed the presence of a highly diverse group of bat-derived viruses related to hepaciviruses and pegiviruses within the family Flaviridae. Subsequent PCR screening of 1,258 bat specimens collected worldwide indicated the presence of these viruses also in North America and Asia. A total of 83 bat-derived viruses were identified, representing an infection rate of nearly 5%. Evolutionary analyses revealed that all known hepaciviruses and pegiviruses, including those previously documented in humans and other primates, fall within the phylogenetic diversity of the bat-derived viruses described here. The prevalence, unprecedented viral biodiversity, phylogenetic divergence, and worldwide distribution of the bat-derived viruses suggest that bats are a major and ancient natural reservoir for both hepaciviruses and pegiviruses and provide insights into the evolutionary history of hepatitis C virus and the human GB viruses.

[1]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[2]  C. Webb,et al.  A comparison of bats and rodents as reservoirs of zoonotic viruses: are bats special? , 2013, Proceedings of the Royal Society B: Biological Sciences.

[3]  Lijun Wu,et al.  Comparative Analysis of Bat Genomes Provides Insight into the Evolution of Flight and Immunity , 2013, Science.

[4]  P. Simmonds,et al.  Nonprimate Hepaciviruses in Domestic Horses, United Kingdom , 2012, Emerging infectious diseases.

[5]  C. Rice,et al.  Serology-Enabled Discovery of Genetically Diverse Hepaciviruses in a New Host , 2012, Journal of Virology.

[6]  Maulik R. Patel,et al.  Convergent Evolution of Escape from Hepaciviral Antagonism in Primates , 2012, PLoS biology.

[7]  M. Knörnschild,et al.  Bats host major mammalian paramyxoviruses , 2012, Nature Communications.

[8]  P. Simmonds,et al.  Evaluating the evidence for virus/host co-evolution. , 2011, Current opinion in virology.

[9]  C. Rice,et al.  Characterization of a canine homolog of hepatitis C virus , 2011, Proceedings of the National Academy of Sciences.

[10]  Jack T. Stapleton,et al.  The GB viruses: a review and proposed classification of GBV-A, GBV-C (HGV), and GBV-D in genus Pegivirus within the family Flaviviridae , 2011, The Journal of general virology.

[11]  J. Epstein,et al.  Investigating the role of bats in emerging zoonoses: Balancing ecology, conservation and public health interest , 2011 .

[12]  Stephen P. Luby,et al.  Identification of GBV-D, a Novel GB-like Flavivirus from Old World Frugivorous Bats (Pteropus giganteus) in Bangladesh , 2010, PLoS pathogens.

[13]  J. d'Alayer,et al.  The Disulfide Bonds in Glycoprotein E2 of Hepatitis C Virus Reveal the Tertiary Organization of the Molecule , 2010, PLoS pathogens.

[14]  P. Woo,et al.  Ecoepidemiology and Complete Genome Comparison of Different Strains of Severe Acute Respiratory Syndrome-Related Rhinolophus Bat Coronavirus in China Reveal Bats as a Reservoir for Acute, Self-Limiting Infection That Allows Recombination Events , 2010, Journal of Virology.

[15]  P. Mavromara,et al.  The HCV ARFP/F/core+1 protein: Production and functional analysis of an unconventional viral product , 2009, IUBMB life.

[16]  J. Simons,et al.  A new arenavirus in a cluster of fatal transplant-associated diseases. , 2008, The New England journal of medicine.

[17]  Kate E. Jones,et al.  Global trends in emerging infectious diseases , 2008, Nature.

[18]  Stephen P. Luby,et al.  Foodborne Transmission of Nipah Virus, Bangladesh , 2006, Emerging infectious diseases.

[19]  H. Field,et al.  Bats: Important Reservoir Hosts of Emerging Viruses , 2006, Clinical Microbiology Reviews.

[20]  M. St. Claire,et al.  Functional analyses of GB virus B p13 protein: development of a recombinant GB virus B hepatitis virus with a p7 protein. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[21]  J. Gonzalez,et al.  Fruit bats as reservoirs of Ebola virus , 2005, Nature.

[22]  Jonathan H. Epstein,et al.  Bats Are Natural Reservoirs of SARS-Like Coronaviruses , 2005, Science.

[23]  Kwok-Hung Chan,et al.  Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Guo-Ping Zhao,et al.  Cross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and human. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[25]  D. Stump,et al.  The hepatitis C virus alternate reading frame (ARF) and its family of novel products: the alternate reading frame protein/F-protein, the double-frameshift protein, and others. , 2005, Seminars in liver disease.

[26]  S. O’Brien,et al.  A Molecular Phylogeny for Bats Illuminates Biogeography and the Fossil Record , 2005, Science.

[27]  P. Simmonds,et al.  Genetic diversity and evolution of hepatitis C virus--15 years on. , 2004, The Journal of general virology.

[28]  T. Gojobori,et al.  Reduction of synonymous substitutions in the core protein gene of hepatitis C virus , 2004, Journal of Molecular Evolution.

[29]  X. L. Liu,et al.  Isolation and Characterization of Viruses Related to the SARS Coronavirus from Animals in Southern China , 2003, Science.

[30]  S. Evans,et al.  The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, Amantadine , 2003, FEBS letters.

[31]  W Ray Kim,et al.  Global epidemiology and burden of hepatitis C. , 2002, Microbes and infection.

[32]  R. Purcell,et al.  Host range studies of GB virus‐B hepatitis agent, the closest relative of hepatitis C virus, in New World monkeys and chimpanzees † , 2001, Journal of medical virology.

[33]  Zhenming Xu,et al.  Synthesis of a novel hepatitis C virus protein by ribosomal frameshift , 2001, The EMBO journal.

[34]  D. Stump,et al.  Evidence for a new hepatitis C virus antigen encoded in an overlapping reading frame. , 2001, RNA.

[35]  H. Field,et al.  Nipah virus infection in bats (order Chiroptera) in peninsular Malaysia. , 2001, Emerging infectious diseases.

[36]  H. Field,et al.  Nipah virus: a recently emergent deadly paramyxovirus. , 2000, Science.

[37]  R. Bartenschlager,et al.  Replication of hepatitis C virus. , 2000, The Journal of general virology.

[38]  R. Charrel,et al.  Phylogenetic analysis of GB viruses A and C: evidence for cospeciation between virus isolates and their primate hosts. , 1999, The Journal of general virology.

[39]  A. Gould,et al.  A morbillivirus that caused fatal disease in horses and humans. , 1995, Science.

[40]  J. Maniloff,et al.  Virus taxonomy : eighth report of the International Committee on Taxonomy of Viruses , 2005 .

[41]  C. Rice,et al.  Processing in the hepatitis C virus E2-NS2 region: identification of p7 and two distinct E2-specific products with different C termini , 1994, Journal of virology.

[42]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[43]  M. Houghton,et al.  Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. , 1989, Science.

[44]  H. Alter.  Discovery of the non-A, non-B hepatitis virus: the end of the beginning or the beginning of the end. , 1989, Transfusion medicine reviews.