English
French
Serology-enabled discovery of genetically diverse hepaciviruses in a new host.
Abstract: Genetic and biological characterization of new hepaciviruses infecting animals contributes to our understanding of the ultimate origins of hepatitis C virus (HCV) infection in humans and dramatically enhances our ability to study its pathogenesis using tractable animal models. Animal homologs of HCV include a recently discovered canine hepacivirus (CHV) and GB virus B (GBV-B), both viruses with largely undetermined natural host ranges. Here we used a versatile serology-based approach to determine the natural host of the only known nonprimate hepacivirus (NPHV), CHV, which is also the closest phylogenetic relative of HCV. Recombinant protein expressed from the helicase domain of CHV NS3 was used as antigen in the luciferase immunoprecipitation system (LIPS) assay to screen several nonprimate animal species. Thirty-six samples from 103 horses were immunoreactive, and viral genomic RNA was present in 8 of the 36 seropositive animals and none of the seronegative animals. Complete genome sequences of these 8 genetically diverse NPHVs showed 14% (range, 6.4% to 17.2%) nucleotide sequence divergence, with most changes occurring at synonymous sites. RNA secondary structure prediction of the 383-base 5' untranslated region of NPHV was refined and extended through mapping of polymorphic sites to unpaired regions or (semi)covariant pairings. Similar approaches were adopted to delineate extensive RNA secondary structures in the coding region of the genome, predicted to form 27 regularly spaced, thermodynamically stable stem-loops. Together, these findings suggest a promising new nonprimate animal model and provide a database that will aid creation of functional NPHV cDNA clones and other novel tools for hepacivirus studies.
Publication Date: 2012-04-04 PubMed ID: 22491452PubMed Central: PMC3372197DOI: 10.1128/JVI.00250-12Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- N.I.H.
- Extramural
- Research Support
- N.I.H.
- Intramural
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research investigated new hepaciviruses found in animals to further our understanding of Hepatitis C virus (HCV) and its origins in humans. The study identified these viruses’ natural hosts and revealed a significant genetic diversity among them, contributing to our capacity to study their pathogenesis using an animal model.
Research Objective
- The aim of the study was to understand the origins of Hepatitis C virus (HCV) in humans by analyzing new hepaciviruses in animals. This was achieved through determining the natural host for the nonprimate hepacivirus (NPHV), a recent canine hepacivirus(CHV).
Methodology
- The researchers utilized a luciferase immunoprecipitation system (LIPS) assay with a recombinant protein created from the CHV NS3 helicase domain as an antigen. This method was used to screen several nonprimate animal species for the presence of the virus.
- The study verified the presence of hepacivirus in horse blood samples, with viral genomic RNA detected in eight out of the 36 immunoreactive samples. No viral genetic material was detected in seronegative samples.
Findings
- The research revealed a 14% nucleotide sequence divergence in the complete genome sequences of the eight genetically diverse NPHVs found in the seropositive samples. The changes primarily occurred at synonymous sites.
- Additionally, predictions of RNA secondary structure of the NPHV were refined through mapping polymorphism sites to unpaired regions or (semi)covariant pairings.
- The research also delineated extensive RNA secondary structures in the genome coding region, predicted to form 27 regularly spaced, stable stem-loops.
Implications
- The research findings offer a new nonprimate animal model to study the origins and pathogenesis of HCV. The genetic diversity observed among the hepaciviruses broadens our understanding of this kind of virus.
- The data obtained will enable the creation of functional NPHV cDNA clones and other innovative tools for hepacivirus studies, opening up new potential directions for future research.
Cite This Article
APA
Burbelo PD, Dubovi EJ, Simmonds P, Medina JL, Henriquez JA, Mishra N, Wagner J, Tokarz R, Cullen JM, Iadarola MJ, Rice CM, Lipkin WI, Kapoor A.
(2012).
Serology-enabled discovery of genetically diverse hepaciviruses in a new host.
J Virol, 86(11), 6171-6178.
https://doi.org/10.1128/JVI.00250-12 Publication
Researcher Affiliations
- Neurobiology and Pain Therapeutics Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.
MeSH Terms
- 5' Untranslated Regions
- Animals
- Antigens, Viral / genetics
- Hepacivirus / genetics
- Hepacivirus / immunology
- Hepacivirus / pathogenicity
- Hepatitis C / immunology
- Hepatitis C / veterinary
- Hepatitis C Antibodies / blood
- Horse Diseases / virology
- Horses
- Host Specificity
- Molecular Sequence Data
- Nucleic Acid Conformation
- RNA, Viral / genetics
- Recombinant Proteins / genetics
- Sequence Analysis, DNA
Grant Funding
- R21 AI081132 / NIAID NIH HHS
- AI070411 / NIAID NIH HHS
- U01 AI070411 / NIAID NIH HHS
- R24 EY017404 / NEI NIH HHS
- 095831 / Wellcome Trust
- U54 AI057158 / NIAID NIH HHS
- Intramural NIH HHS
- AI081132 / NIAID NIH HHS
- EY017404 / NEI NIH HHS
- R21 AI090196 / NIAID NIH HHS
- R01 AI079231 / NIAID NIH HHS
- AI57158 / NIAID NIH HHS
- AI079231 / NIAID NIH HHS
- AI090196 / NIAID NIH HHS
References
This article includes 41 references
- Aguilar PV, Estrada-Franco JG, Navarro-Lopez R, Ferro C, Haddow AD, Weaver SC. Endemic Venezuelan equine encephalitis in the Americas: hidden under the dengue umbrella.. Future Virol 2011;6(6):721-740.
- Bruderer U, Swam H, Haas B, Visser N, Brocchi E, Grazioli S, Esterhuysen JJ, Vosloo W, Forsyth M, Aggarwal N, Cox S, Armstrong R, Anderson J. Differentiating infection from vaccination in foot-and-mouth-disease: evaluation of an ELISA based on recombinant 3ABC.. Vet Microbiol 2004 Jul 14;101(3):187-97.
- Bukh J. Hepatitis C homolog in dogs with respiratory illness.. Proc Natl Acad Sci U S A 2011 Aug 2;108(31):12563-4.
- Bukh J, Apgar CL, Govindarajan S, Purcell RH. Host range studies of GB virus-B hepatitis agent, the closest relative of hepatitis C virus, in New World monkeys and chimpanzees.. J Med Virol 2001 Dec;65(4):694-7.
- Bukh J, Apgar CL, Yanagi M. Toward a surrogate model for hepatitis C virus: An infectious molecular clone of the GB virus-B hepatitis agent.. Virology 1999 Sep 30;262(2):470-8.
- Burbelo PD, Bren KE, Ching KH, Gogineni ES, Kottilil S, Cohen JI, Kovacs JA, Iadarola MJ. LIPS arrays for simultaneous detection of antibodies against partial and whole proteomes of HCV, HIV and EBV.. Mol Biosyst 2011 May;7(5):1453-62.
- Burbelo PD, Ching KH, Esper F, Iadarola MJ, Delwart E, Lipkin WI, Kapoor A. Serological studies confirm the novel astrovirus HMOAstV-C as a highly prevalent human infectious agent.. PLoS One 2011;6(8):e22576.
- Burbelo PD, Ching KH, Klimavicz CM, Iadarola MJ. Antibody profiling by Luciferase Immunoprecipitation Systems (LIPS).. J Vis Exp 2009 Oct 7;(32).
- Burbelo PD, Ching KH, Mattson TL, Light JS, Bishop LR, Kovacs JA. Rapid antibody quantification and generation of whole proteome antibody response profiles using LIPS (luciferase immunoprecipitation systems).. Biochem Biophys Res Commun 2007 Jan 26;352(4):889-95.
- Burbelo PD, Goldman R, Mattson TL. A simplified immunoprecipitation method for quantitatively measuring antibody responses in clinical sera samples by using mammalian-produced Renilla luciferase-antigen fusion proteins.. BMC Biotechnol 2005 Aug 18;5:22.
- Burbelo PD, Kovacs JA, Ching KH, Issa AT, Iadarola MJ, Murphy AA, Schlaak JF, Masur H, Polis MA, Kottilil S. Proteome-wide anti-hepatitis C virus (HCV) and anti-HIV antibody profiling for predicting and monitoring the response to HCV therapy in HIV-coinfected patients.. J Infect Dis 2010 Sep 15;202(6):894-8.
- . West Nile virus disease and other arboviral diseases--United States, 2010.. MMWR Morb Mortal Wkly Rep 2011 Aug 5;60(30):1009-13.
- Davis M, Sagan SM, Pezacki JP, Evans DJ, Simmonds P. Bioinformatic and physical characterizations of genome-scale ordered RNA structure in mammalian RNA viruses.. J Virol 2008 Dec;82(23):11824-36.
- Dolgin E. Research technique: the murine candidate.. Nature 2011 Jun 8;474(7350):S14-5.
- Gruber AR, Lorenz R, Bernhart SH, Neubu00f6ck R, Hofacker IL. The Vienna RNA websuite.. Nucleic Acids Res 2008 Jul 1;36(Web Server issue):W70-4.
- Honda M, Brown EA, Lemon SM. Stability of a stem-loop involving the initiator AUG controls the efficiency of internal initiation of translation on hepatitis C virus RNA.. RNA 1996 Oct;2(10):955-68.
- Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA.. Science 2005 Sep 2;309(5740):1577-81.
- Kapoor A, Li L, Victoria J, Oderinde B, Mason C, Pandey P, Zaidi SZ, Delwart E. Multiple novel astrovirus species in human stool.. J Gen Virol 2009 Dec;90(Pt 12):2965-2972.
- Kapoor A, Mehta N, Dubovi EJ, Simmonds P, Govindasamy L, Medina JL, Street C, Shields S, Lipkin WI. Characterization of novel canine bocaviruses and their association with respiratory disease.. J Gen Virol 2012 Feb;93(Pt 2):341-346.
- Kapoor A, Mehta N, Esper F, Poljsak-Prijatelj M, Quan PL, Qaisar N, Delwart E, Lipkin WI. Identification and characterization of a new bocavirus species in gorillas.. PLoS One 2010 Jul 23;5(7):e11948.
- Kapoor A, Simmonds P, Gerold G, Qaisar N, Jain K, Henriquez JA, Firth C, Hirschberg DL, Rice CM, Shields S, Lipkin WI. Characterization of a canine homolog of hepatitis C virus.. Proc Natl Acad Sci U S A 2011 Jul 12;108(28):11608-13.
- Kapoor A, Simmonds P, Lipkin WI, Zaidi S, Delwart E. Use of nucleotide composition analysis to infer hosts for three novel picorna-like viruses.. J Virol 2010 Oct;84(19):10322-8.
- Kapoor A, Victoria J, Simmonds P, Slikas E, Chieochansin T, Naeem A, Shaukat S, Sharif S, Alam MM, Angez M, Wang C, Shafer RW, Zaidi S, Delwart E. A highly prevalent and genetically diversified Picornaviridae genus in South Asian children.. Proc Natl Acad Sci U S A 2008 Dec 23;105(51):20482-7.
- Kapoor A, Victoria J, Simmonds P, Wang C, Shafer RW, Nims R, Nielsen O, Delwart E. A highly divergent picornavirus in a marine mammal.. J Virol 2008 Jan;82(1):311-20.
- Kosakovsky Pond SL, Posada D, Gravenor MB, Woelk CH, Frost SD. Automated phylogenetic detection of recombination using a genetic algorithm.. Mol Biol Evol 2006 Oct;23(10):1891-901.
- Lindenbach BD, Evans MJ, Syder AJ, Wu00f6lk B, Tellinghuisen TL, Liu CC, Maruyama T, Hynes RO, Burton DR, McKeating JA, Rice CM. Complete replication of hepatitis C virus in cell culture.. Science 2005 Jul 22;309(5734):623-6.
- Lipkin WI. Microbe hunting.. Microbiol Mol Biol Rev 2010 Sep;74(3):363-77.
- Menne S, Cote PJ. The woodchuck as an animal model for pathogenesis and therapy of chronic hepatitis B virus infection.. World J Gastroenterol 2007 Jan 7;13(1):104-24.
- Muerhoff AS, Leary TP, Simons JN, Pilot-Matias TJ, Dawson GJ, Erker JC, Chalmers ML, Schlauder GG, Desai SM, Mushahwar IK. Genomic organization of GB viruses A and B: two new members of the Flaviviridae associated with GB agent hepatitis.. J Virol 1995 Sep;69(9):5621-30.
- Murray CL, Rice CM. Turning hepatitis C into a real virus.. Annu Rev Microbiol 2011;65:307-27.
- Nam JH, Faulk K, Engle RE, Govindarajan S, St Claire M, Bukh J. In vivo analysis of the 3' untranslated region of GB virus B after in vitro mutagenesis of an infectious cDNA clone: persistent infection in a transfected tamarin.. J Virol 2004 Sep;78(17):9389-99.
- Pietschmann T, Lohmann V, Kaul A, Krieger N, Rinck G, Rutter G, Strand D, Bartenschlager R. Persistent and transient replication of full-length hepatitis C virus genomes in cell culture.. J Virol 2002 Apr;76(8):4008-21.
- Pond SL, Frost SD, Muse SV. HyPhy: hypothesis testing using phylogenies.. Bioinformatics 2005 Mar 1;21(5):676-9.
- Simmonds P. SSE: a nucleotide and amino acid sequence analysis platform.. BMC Res Notes 2012 Jan 20;5:50.
- Simmonds P, Tuplin A, Evans DJ. Detection of genome-scale ordered RNA structure (GORS) in genomes of positive-stranded RNA viruses: Implications for virus evolution and host persistence.. RNA 2004 Sep;10(9):1337-51.
- Simons JN, Leary TP, Dawson GJ, Pilot-Matias TJ, Muerhoff AS, Schlauder GG, Desai SM, Mushahwar IK. Isolation of novel virus-like sequences associated with human hepatitis.. Nat Med 1995 Jun;1(6):564-9.
- Simons JN, Pilot-Matias TJ, Leary TP, Dawson GJ, Desai SM, Schlauder GG, Muerhoff AS, Erker JC, Buijk SL, Chalmers ML. Identification of two flavivirus-like genomes in the GB hepatitis agent.. Proc Natl Acad Sci U S A 1995 Apr 11;92(8):3401-5.
- Stapleton JT, Foung S, Muerhoff AS, Bukh J, Simmonds P. The GB viruses: a review and proposed classification of GBV-A, GBV-C (HGV), and GBV-D in genus Pegivirus within the family Flaviviridae.. J Gen Virol 2011 Feb;92(Pt 2):233-46.
- Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S. MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods.. Mol Biol Evol 2011 Oct;28(10):2731-9.
- Wakita T, Pietschmann T, Kato T, Date T, Miyamoto M, Zhao Z, Murthy K, Habermann A, Kru00e4usslich HG, Mizokami M, Bartenschlager R, Liang TJ. Production of infectious hepatitis C virus in tissue culture from a cloned viral genome.. Nat Med 2005 Jul;11(7):791-6.
- Wobus CE, Thackray LB, Virgin HW 4th. Murine norovirus: a model system to study norovirus biology and pathogenesis.. J Virol 2006 Jun;80(11):5104-12.
Citations
This article has been cited 125 times.Secure Payments
Satisfaction Guarantee
We offer a 60-day guarantee to ensure you are completely satisfied.
Fast & Free Shipping
We provide fast and free shipping on all orders over $40.