FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Journal of virology2016; 90(10); 5075-5089; doi: 10.1128/JVI.00132-16

Ion Channel Function and Cross-Species Determinants in Viral Assembly of Nonprimate Hepacivirus p7.

Abstract: Nonprimate hepacivirus (NPHV), the closest homolog of hepatitis C virus (HCV) described to date, has recently been discovered in horses. Even though the two viruses share a similar genomic organization, conservation of the encoded hepaciviral proteins remains undetermined. The HCV p7 protein is localized within endoplasmic reticulum (ER) membranes and is important for the production of infectious particles. In this study, we analyzed the structural and functional features of NPHV p7 in addition to its role during virus assembly. Three-dimensional homology models for NPHV p7 using various nuclear magnetic resonance spectroscopy (NMR) structures were generated, highlighting the conserved residues important for ion channel function. By applying a liposome permeability assay, we observed that NPHV p7 exhibited liposome permeability features similar to those of HCV p7, indicative of similar ion channel activity. Next, we characterized the viral protein using a p7-based trans-complementation approach. A similar subcellular localization pattern at the ER membrane was observed, although production of infectious particles was likely hindered by genetic incompatibilities with HCV proteins. To further characterize these cross-species constraints, chimeric viruses were constructed by substituting different regions of HCV p7 with NPHV p7. The N terminus and transmembrane domains were nonexchangeable and therefore constitute a cross-species barrier in hepaciviral assembly. In contrast, the basic loop and the C terminus of NPHV p7 were readily exchangeable, allowing production of infectious trans-complemented viral particles. In conclusion, comparison of NPHV and HCV p7 revealed structural and functional homology of these proteins, including liposome permeability, and broadly acting determinants that modulate hepaciviral virion assembly and contribute to the host-species barrier were identified. The recent discovery of new relatives of hepatitis C virus (HCV) enables for the first time the study of cross-species determinants shaping hepaciviral pathogenesis. Nonprimate hepacivirus (NPHV) was described to infect horses and represents so far the closest homolog of HCV. Both viruses encode the same viral proteins; however, NPHV protein functions remain poorly understood. In this study, we aimed to dissect NPHV p7 on a structural and functional level. By using various NMR structures of HCV p7 as templates, three-dimensional homology models for NPHV p7 were generated, highlighting conserved residues that are important for ion channel function. A p7-based trans-complementation approach and the construction of NPHV/HCV p7 chimeric viruses showed that the N terminus and transmembrane domains were nonexchangeable. In contrast, the basic loop and the C terminus of NPHV p7 were readily exchangeable, allowing production of infectious viral particles. These results identify species-specific constraints as well as exchangeable determinants in hepaciviral assembly.
Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Get Full Text
Publication Date: 2016-04-29 PubMed ID: 26962224PubMed Central: PMC4859704DOI: 10.1128/JVI.00132-16Google 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.
LinkedInCopy
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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 article explores the structural and functional features of Nonprimate Hepacivirus (NPHV) p7. The study generated three-dimensional models to pinpoint ion channel function and utilized a liposome permeability test to assess similarities to Hepatitis C virus (HCV) p7, revealing species-specific constraints and exchangeable determinants in Hepaciviral assembly.

Introduction and Background

  • The article begins by providing a background on Hepatitis C and Nonprimate Hepacivirus (NPHV). It explains the recognition of NPHV as the closest counterpart to Hepatitis C virus (HCV) found in horses but acknowledges that the conservation of the encoded Hepaciviral proteins remains uncertain.
  • The research highlights the importance of the p7 protein, which is located within the endoplasmic reticulum membranes, to the production of infectious particles.

The Study on NPHV p7

  • The researchers analyzed the structural and functional features of NPHV p7 and its role during virus assembly. They used different nuclear magnetic resonance spectroscopy (NMR) structures to create three-dimensional homology models, showcasing the conserved residues vital for ion channel functionality.
  • The study used a liposome permeability assay and found that the NPHV p7 exhibited similar characteristics to HCV p7 suggesting a similar ion channel activity.

Assessing the Constraints and Determinants in Hepaciviral Assembly

  • To understand the limiting factors affecting the replication abilities between the two species, scientists constructed hybrid versions of the virus by substituting various sections of HCV p7 with NPHV p7.
  • The research found that the N terminus and transmembrane domains of NPHV were not interchangeable with those of HCV, implying a barrier to cross-species Hepaciviral assembly.
  • Conversely, they discovered that the basic loop and the C terminus of NPHV p7 could be easily substituted, allowing for the production of infectious trans-complemented viral particles.

Research Findings and Conclusion

  • Overall, the study found structural and functional similarities between NPHV and HCV p7 proteins, as well as identifying factors that modulate hepaciviral virion assembly and contribute to the host-species barrier.
  • Through these findings, the scientists were able to better understand the cross-species determinants that define hepaciviral pathogenesis.

Cite This Article

APA
Walter S, Bollenbach A, Doerrbecker J, Pfaender S, Brown RJP, Vieyres G, Scott C, Foster R, Kumar A, Zitzmann N, Griffin S, Penin F, Pietschmann T, Steinmann E. (2016). Ion Channel Function and Cross-Species Determinants in Viral Assembly of Nonprimate Hepacivirus p7. J Virol, 90(10), 5075-5089. https://doi.org/10.1128/JVI.00132-16

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 90
Issue: 10
Pages: 5075-5089

Researcher Affiliations

Walter, Stephanie
  • Institute for Experimental Virology, TWINCORE, Hannover, Germany.
Bollenbach, Alexander
  • Institute for Experimental Virology, TWINCORE, Hannover, Germany.
Doerrbecker, Juliane
  • Institute for Experimental Virology, TWINCORE, Hannover, Germany.
Pfaender, Stephanie
  • Institute for Experimental Virology, TWINCORE, Hannover, Germany.
Brown, Richard J P
  • Institute for Experimental Virology, TWINCORE, Hannover, Germany.
Vieyres, Gabrielle
  • Institute for Experimental Virology, TWINCORE, Hannover, Germany.
Scott, Claire
  • Leeds Institute of Cancer & Pathology, University of Leeds, St James' University Hospital, Leeds, Great Britain.
Foster, Richard
  • Leeds Institute of Cancer & Pathology, University of Leeds, St James' University Hospital, Leeds, Great Britain.
Kumar, Abhinav
  • Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, Great Britain.
Zitzmann, Nicole
  • Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, Great Britain.
Griffin, Stephen
  • Leeds Institute of Cancer & Pathology, University of Leeds, St James' University Hospital, Leeds, Great Britain.
Penin, François
  • Institut de Biologie et Chimie des Protéines, CNRS, UMR 5086, Laboratoire International Associé CNRS-UIUC, Labex Ecofect, University of Lyon, Lyon, France.
Pietschmann, Thomas
  • Institute for Experimental Virology, TWINCORE, Hannover, Germany.
Steinmann, Eike
  • Institute for Experimental Virology, TWINCORE, Hannover, Germany Eike.Steinmann@twincore.de.

MeSH Terms

  • Animals
  • Cell Line
  • Endoplasmic Reticulum / metabolism
  • Genetic Complementation Test
  • Hepacivirus / chemistry
  • Hepacivirus / genetics
  • Hepacivirus / physiology
  • Horses
  • Humans
  • Ion Channels / chemistry
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Liposomes
  • Models, Molecular
  • Permeability
  • Species Specificity
  • Viral Proteins / chemistry
  • Viral Proteins / genetics
  • Viral Proteins / metabolism
  • Virus Assembly
  • Virus Replication

Grant Funding

  • G0700124 / Medical Research Council
  • MC_PC_13066 / Medical Research Council

References

This article includes 63 references
  1. 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.
    doi: 10.1073/pnas.1101794108pmc: PMC3136326pubmed: 21610165google scholar: lookup
  2. 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. Serology-enabled discovery of genetically diverse hepaciviruses in a new host.. J Virol 2012 Jun;86(11):6171-8.
    doi: 10.1128/JVI.00250-12pmc: PMC3372197pubmed: 22491452google scholar: lookup
  3. Drexler JF, Corman VM, Müller MA, Lukashev AN, Gmyl A, Coutard B, Adam A, Ritz D, Leijten LM, van Riel D, Kallies R, Klose SM, Gloza-Rausch F, Binger T, Annan A, Adu-Sarkodie Y, Oppong S, Bourgarel M, Rupp D, Hoffmann B, Schlegel M, Kümmerer BM, Krüger DH, Schmidt-Chanasit J, Setién AA, Cottontail VM, Hemachudha T, Wacharapluesadee S, Osterrieder K, Bartenschlager R, Matthee S, Beer M, Kuiken T, Reusken C, Leroy EM, Ulrich RG, Drosten C. Evidence for novel hepaciviruses in rodents.. PLoS Pathog 2013;9(6):e1003438.
    doi: 10.1371/journal.ppat.1003438pmc: PMC3688547pubmed: 23818848google scholar: lookup
  4. Quan PL, Firth C, Conte JM, Williams SH, Zambrana-Torrelio CM, Anthony SJ, Ellison JA, Gilbert AT, Kuzmin IV, Niezgoda M, Osinubi MO, Recuenco S, Markotter W, Breiman RF, Kalemba L, Malekani J, Lindblade KA, Rostal MK, Ojeda-Flores R, Suzan G, Davis LB, Blau DM, Ogunkoya AB, Alvarez Castillo DA, Moran D, Ngam S, Akaibe D, Agwanda B, Briese T, Epstein JH, Daszak P, Rupprecht CE, Holmes EC, Lipkin WI. Bats are a major natural reservoir for hepaciviruses and pegiviruses.. Proc Natl Acad Sci U S A 2013 May 14;110(20):8194-9.
    doi: 10.1073/pnas.1303037110pmc: PMC3657805pubmed: 23610427google scholar: lookup
  5. Kapoor A, Simmonds P, Scheel TK, Hjelle B, Cullen JM, Burbelo PD, Chauhan LV, Duraisamy R, Sanchez Leon M, Jain K, Vandegrift KJ, Calisher CH, Rice CM, Lipkin WI. Identification of rodent homologs of hepatitis C virus and pegiviruses.. mBio 2013 Apr 9;4(2):e00216-13.
    doi: 10.1128/mBio.00216-13pmc: PMC3622934pubmed: 23572554google scholar: lookup
  6. Lauck M, Sibley SD, Lara J, Purdy MA, Khudyakov Y, Hyeroba D, Tumukunde A, Weny G, Switzer WM, Chapman CA, Hughes AL, Friedrich TC, O'Connor DH, Goldberg TL. A novel hepacivirus with an unusually long and intrinsically disordered NS5A protein in a wild Old World primate.. J Virol 2013 Aug;87(16):8971-81.
    doi: 10.1128/JVI.00888-13pmc: PMC3754081pubmed: 23740998google scholar: lookup
  7. Firth C, Bhat M, Firth MA, Williams SH, Frye MJ, Simmonds P, Conte JM, Ng J, Garcia J, Bhuva NP, Lee B, Che X, Quan PL, Lipkin WI. Detection of zoonotic pathogens and characterization of novel viruses carried by commensal Rattus norvegicus in New York City.. mBio 2014 Oct 14;5(5):e01933-14.
    doi: 10.1128/mBio.01933-14pmc: PMC4205793pubmed: 25316698google scholar: lookup
  8. Corman VM, Grundhoff A, Baechlein C, Fischer N, Gmyl A, Wollny R, Dei D, Ritz D, Binger T, Adankwah E, Marfo KS, Annison L, Annan A, Adu-Sarkodie Y, Oppong S, Becher P, Drosten C, Drexler JF. Highly divergent hepaciviruses from African cattle.. J Virol 2015 Jun;89(11):5876-82.
    doi: 10.1128/JVI.00393-15pmc: PMC4442428pubmed: 25787289google scholar: lookup
  9. Baechlein C, Fischer N, Grundhoff A, Alawi M, Indenbirken D, Postel A, Baron AL, Offinger J, Becker K, Beineke A, Rehage J, Becher P. Identification of a Novel Hepacivirus in Domestic Cattle from Germany.. J Virol 2015 Jul;89(14):7007-15.
    doi: 10.1128/JVI.00534-15pmc: PMC4473572pubmed: 25926652google scholar: lookup
  10. Scheel TK, Simmonds P, Kapoor A. Surveying the global virome: identification and characterization of HCV-related animal hepaciviruses.. Antiviral Res 2015 Mar;115:83-93.
    doi: 10.1016/j.antiviral.2014.12.014pmc: PMC5081135pubmed: 25545071google scholar: lookup
  11. Pfaender S, Brown RJ, Pietschmann T, Steinmann E. Natural reservoirs for homologs of hepatitis C virus.. Emerg Microbes Infect 2014 Mar;3(3):e21.
    doi: 10.1038/emi.2014.19pmc: PMC3974340pubmed: 26038514google scholar: lookup
  12. . Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.. Lancet 2015 Aug 22;386(9995):743-800.
    doi: 10.1016/S0140-6736(15)60692-4pmc: PMC4561509pubmed: 26063472google scholar: lookup
  13. Hoofnagle JH. Hepatitis C: the clinical spectrum of disease.. Hepatology 1997 Sep;26(3 Suppl 1):15S-20S.
    doi: 10.1002/hep.510260703pubmed: 9305658google scholar: lookup
  14. Pawlotsky JM. New hepatitis C therapies: the toolbox, strategies, and challenges.. Gastroenterology 2014 May;146(5):1176-92.
    doi: 10.1053/j.gastro.2014.03.003pubmed: 24631495google scholar: lookup
  15. Bartenschlager R, Frese M, Pietschmann T. Novel insights into hepatitis C virus replication and persistence.. Adv Virus Res 2004;63:71-180.
    doi: 10.1016/S0065-3527(04)63002-8pubmed: 15530561google scholar: lookup
  16. Scott C, Griffin S. Viroporins: structure, function and potential as antiviral targets.. J Gen Virol 2015 Aug;96(8):2000-2027.
    doi: 10.1099/vir.0.000201pubmed: 26023149google scholar: lookup
  17. Carrère-Kremer S, Montpellier-Pala C, Cocquerel L, Wychowski C, Penin F, Dubuisson J. Subcellular localization and topology of the p7 polypeptide of hepatitis C virus.. J Virol 2002 Apr;76(8):3720-30.
    doi: 10.1128/JVI.76.8.3720-3730.2002pmc: PMC136108pubmed: 11907211google scholar: lookup
  18. Isherwood BJ, Patel AH. Analysis of the processing and transmembrane topology of the E2p7 protein of hepatitis C virus.. J Gen Virol 2005 Mar;86(Pt 3):667-676.
    doi: 10.1099/vir.0.80737-0pubmed: 15722527google scholar: lookup
  19. Chandler DE, Penin F, Schulten K, Chipot C. The p7 protein of hepatitis C virus forms structurally plastic, minimalist ion channels.. PLoS Comput Biol 2012;8(9):e1002702.
    doi: 10.1371/journal.pcbi.1002702pmc: PMC3447957pubmed: 23028296google scholar: lookup
  20. Luik P, Chew C, Aittoniemi J, Chang J, Wentworth P Jr, Dwek RA, Biggin PC, Vénien-Bryan C, Zitzmann N. The 3-dimensional structure of a hepatitis C virus p7 ion channel by electron microscopy.. Proc Natl Acad Sci U S A 2009 Aug 4;106(31):12712-6.
    doi: 10.1073/pnas.0905966106pmc: PMC2722341pubmed: 19590017google scholar: lookup
  21. Griffin SD, Beales LP, Clarke DS, Worsfold O, Evans SD, Jaeger J, Harris MP, Rowlands DJ. The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, Amantadine.. FEBS Lett 2003 Jan 30;535(1-3):34-8.
    doi: 10.1016/S0014-5793(02)03851-6pubmed: 12560074google scholar: lookup
  22. Clarke D, Griffin S, Beales L, Gelais CS, Burgess S, Harris M, Rowlands D. Evidence for the formation of a heptameric ion channel complex by the hepatitis C virus p7 protein in vitro.. J Biol Chem 2006 Dec 1;281(48):37057-68.
    doi: 10.1074/jbc.M602434200pubmed: 17032656google scholar: lookup
  23. Montserret R, Saint N, Vanbelle C, Salvay AG, Simorre JP, Ebel C, Sapay N, Renisio JG, Böckmann A, Steinmann E, Pietschmann T, Dubuisson J, Chipot C, Penin F. NMR structure and ion channel activity of the p7 protein from hepatitis C virus.. J Biol Chem 2010 Oct 8;285(41):31446-61.
    doi: 10.1074/jbc.M110.122895pmc: PMC2951219pubmed: 20667830google scholar: lookup
  24. Foster TL, Thompson GS, Kalverda AP, Kankanala J, Bentham M, Wetherill LF, Thompson J, Barker AM, Clarke D, Noerenberg M, Pearson AR, Rowlands DJ, Homans SW, Harris M, Foster R, Griffin S. Structure-guided design affirms inhibitors of hepatitis C virus p7 as a viable class of antivirals targeting virion release.. Hepatology 2014 Feb;59(2):408-22.
    doi: 10.1002/hep.26685pmc: PMC4298801pubmed: 24022996google scholar: lookup
  25. Cook GA, Dawson LA, Tian Y, Opella SJ. Three-dimensional structure and interaction studies of hepatitis C virus p7 in 1,2-dihexanoyl-sn-glycero-3-phosphocholine by solution nuclear magnetic resonance.. Biochemistry 2013 Aug 6;52(31):5295-303.
    doi: 10.1021/bi4006623pmc: PMC3855088pubmed: 23841474google scholar: lookup
  26. OuYang B, Xie S, Berardi MJ, Zhao X, Dev J, Yu W, Sun B, Chou JJ. Unusual architecture of the p7 channel from hepatitis C virus.. Nature 2013 Jun 27;498(7455):521-5.
    doi: 10.1038/nature12283pmc: PMC3725310pubmed: 23739335google scholar: lookup
  27. Steinmann E, Penin F, Kallis S, Patel AH, Bartenschlager R, Pietschmann T. Hepatitis C virus p7 protein is crucial for assembly and release of infectious virions.. PLoS Pathog 2007 Jul;3(7):e103.
    doi: 10.1371/journal.ppat.0030103pmc: PMC1924870pubmed: 17658949google scholar: lookup
  28. Jones CT, Murray CL, Eastman DK, Tassello J, Rice CM. Hepatitis C virus p7 and NS2 proteins are essential for production of infectious virus.. J Virol 2007 Aug;81(16):8374-83.
    doi: 10.1128/JVI.00690-07pmc: PMC1951341pubmed: 17537845google scholar: lookup
  29. Madan V, Bartenschlager R. Structural and Functional Properties of the Hepatitis C Virus p7 Viroporin.. Viruses 2015 Aug 6;7(8):4461-81.
    doi: 10.3390/v7082826pmc: PMC4576187pubmed: 26258788google scholar: lookup
  30. Steinmann E, Pietschmann T. Hepatitis C virus p7-a viroporin crucial for virus assembly and an emerging target for antiviral therapy.. Viruses 2010 Sep;2(9):2078-2095.
    doi: 10.3390/v2092078pmc: PMC3185753pubmed: 21994720google scholar: lookup
  31. Pfaender S, Cavalleri JM, Walter S, Doerrbecker J, Campana B, Brown RJ, Burbelo PD, Postel A, Hahn K, Anggakusuma, Riebesehl N, Baumgärtner W, Becher P, Heim MH, Pietschmann T, Feige K, Steinmann E. Clinical course of infection and viral tissue tropism of hepatitis C virus-like nonprimate hepaciviruses in horses.. Hepatology 2015 Feb;61(2):447-59.
    doi: 10.1002/hep.27440pubmed: 25212983google scholar: lookup
  32. Tanaka T, Kasai H, Yamashita A, Okuyama-Dobashi K, Yasumoto J, Maekawa S, Enomoto N, Okamoto T, Matsuura Y, Morimatsu M, Manabe N, Ochiai K, Yamashita K, Moriishi K. Hallmarks of hepatitis C virus in equine hepacivirus.. J Virol 2014 Nov;88(22):13352-66.
    doi: 10.1128/JVI.02280-14pmc: PMC4249100pubmed: 25210167google scholar: lookup
  33. Parera M, Martrus G, Franco S, Clotet B, Martinez MA. Canine hepacivirus NS3 serine protease can cleave the human adaptor proteins MAVS and TRIF.. PLoS One 2012;7(8):e42481.
    doi: 10.1371/journal.pone.0042481pmc: PMC3411667pubmed: 22870331google scholar: lookup
  34. Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: Molecular Evolutionary Genetics Analysis version 6.0.. Mol Biol Evol 2013 Dec;30(12):2725-9.
    doi: 10.1093/molbev/mst197pmc: PMC3840312pubmed: 24132122google scholar: lookup
  35. Thompson JD, Higgins DG, Gibson TJ. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice.. Nucleic Acids Res 1994 Nov 11;22(22):4673-80.
    doi: 10.1093/nar/22.22.4673pmc: PMC308517pubmed: 7984417google scholar: lookup
  36. Biasini M, Bienert S, Waterhouse A, Arnold K, Studer G, Schmidt T, Kiefer F, Gallo Cassarino T, Bertoni M, Bordoli L, Schwede T. SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information.. Nucleic Acids Res 2014 Jul;42(Web Server issue):W252-8.
    doi: 10.1093/nar/gku340pmc: PMC4086089pubmed: 24782522google scholar: lookup
  37. Kalita MM, Griffin S, Chou JJ, Fischer WB. Genotype-specific differences in structural features of hepatitis C virus (HCV) p7 membrane protein.. Biochim Biophys Acta 2015 Jun;1848(6):1383-92.
    doi: 10.1016/j.bbamem.2015.03.006pmc: PMC7094707pubmed: 25772504google scholar: lookup
  38. Humphrey W, Dalke A, Schulten K. VMD: visual molecular dynamics.. J Mol Graph 1996 Feb;14(1):33-8, 27-8.
    doi: 10.1016/0263-7855(96)00018-5pubmed: 8744570google scholar: lookup
  39. StGelais C, Tuthill TJ, Clarke DS, Rowlands DJ, Harris M, Griffin S. Inhibition of hepatitis C virus p7 membrane channels in a liposome-based assay system.. Antiviral Res 2007 Oct;76(1):48-58.
    doi: 10.1016/j.antiviral.2007.05.001pubmed: 17574688google scholar: lookup
  40. Steinmann E, Brohm C, Kallis S, Bartenschlager R, Pietschmann T. Efficient trans-encapsidation of hepatitis C virus RNAs into infectious virus-like particles.. J Virol 2008 Jul;82(14):7034-46.
    doi: 10.1128/JVI.00118-08pmc: PMC2446957pubmed: 18480457google scholar: lookup
  41. Brohm C, Steinmann E, Friesland M, Lorenz IC, Patel A, Penin F, Bartenschlager R, Pietschmann T. Characterization of determinants important for hepatitis C virus p7 function in morphogenesis by using trans-complementation.. J Virol 2009 Nov;83(22):11682-93.
    doi: 10.1128/JVI.00691-09pmc: PMC2772676pubmed: 19726506google scholar: lookup
  42. Vieyres G, Brohm C, Friesland M, Gentzsch J, Wölk B, Roingeard P, Steinmann E, Pietschmann T. Subcellular localization and function of an epitope-tagged p7 viroporin in hepatitis C virus-producing cells.. J Virol 2013 Feb;87(3):1664-78.
    doi: 10.1128/JVI.02782-12pmc: PMC3554161pubmed: 23175364google scholar: lookup
  43. Pietschmann T, Kaul A, Koutsoudakis G, Shavinskaya A, Kallis S, Steinmann E, Abid K, Negro F, Dreux M, Cosset FL, Bartenschlager R. Construction and characterization of infectious intragenotypic and intergenotypic hepatitis C virus chimeras.. Proc Natl Acad Sci U S A 2006 May 9;103(19):7408-13.
    doi: 10.1073/pnas.0504877103pmc: PMC1455439pubmed: 16651538google scholar: lookup
  44. Appel N, Zayas M, Miller S, Krijnse-Locker J, Schaller T, Friebe P, Kallis S, Engel U, Bartenschlager R. Essential role of domain III of nonstructural protein 5A for hepatitis C virus infectious particle assembly.. PLoS Pathog 2008 Mar 28;4(3):e1000035.
    doi: 10.1371/journal.ppat.1000035pmc: PMC2268006pubmed: 18369481google scholar: lookup
  45. Keck ZY, Xia J, Wang Y, Wang W, Krey T, Prentoe J, Carlsen T, Li AY, Patel AH, Lemon SM, Bukh J, Rey FA, Foung SK. Human monoclonal antibodies to a novel cluster of conformational epitopes on HCV E2 with resistance to neutralization escape in a genotype 2a isolate.. PLoS Pathog 2012;8(4):e1002653.
    doi: 10.1371/journal.ppat.1002653pmc: PMC3325216pubmed: 22511875google scholar: lookup
  46. Lindenbach BD, Evans MJ, Syder AJ, Wölk 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.
    doi: 10.1126/science.1114016pubmed: 15947137google scholar: lookup
  47. Dentzer TG, Lorenz IC, Evans MJ, Rice CM. Determinants of the hepatitis C virus nonstructural protein 2 protease domain required for production of infectious virus.. J Virol 2009 Dec;83(24):12702-13.
    doi: 10.1128/JVI.01184-09pmc: PMC2786863pubmed: 19812162google scholar: lookup
  48. Owsianka A, Tarr AW, Juttla VS, Lavillette D, Bartosch B, Cosset FL, Ball JK, Patel AH. Monoclonal antibody AP33 defines a broadly neutralizing epitope on the hepatitis C virus E2 envelope glycoprotein.. J Virol 2005 Sep;79(17):11095-104.
    doi: 10.1128/JVI.79.17.11095-11104.2005pmc: PMC1193588pubmed: 16103160google scholar: lookup
  49. Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.. Nucleic Acids Res 1997 Sep 1;25(17):3389-402.
    doi: 10.1093/nar/25.17.3389pmc: PMC146917pubmed: 9254694google scholar: lookup
  50. Pearson WR. Searching protein sequence libraries: comparison of the sensitivity and selectivity of the Smith-Waterman and FASTA algorithms.. Genomics 1991 Nov;11(3):635-50.
    doi: 10.1016/0888-7543(91)90071-Lpubmed: 1774068google scholar: lookup
  51. Smith DB, Bukh J, Kuiken C, Muerhoff AS, Rice CM, Stapleton JT, Simmonds P. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource.. Hepatology 2014 Jan;59(1):318-27.
    doi: 10.1002/hep.26744pmc: PMC4063340pubmed: 24115039google scholar: lookup
  52. Simmonds P, Bukh J, Combet C, Deléage G, Enomoto N, Feinstone S, Halfon P, Inchauspé G, Kuiken C, Maertens G, Mizokami M, Murphy DG, Okamoto H, Pawlotsky JM, Penin F, Sablon E, Shin-I T, Stuyver LJ, Thiel HJ, Viazov S, Weiner AJ, Widell A. Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes.. Hepatology 2005 Oct;42(4):962-73.
    doi: 10.1002/hep.20819pubmed: 16149085google scholar: lookup
  53. Nieva JL, Madan V, Carrasco L. Viroporins: structure and biological functions.. Nat Rev Microbiol 2012 Jul 2;10(8):563-74.
    doi: 10.1038/nrmicro2820pmc: PMC7097105pubmed: 22751485google scholar: lookup
  54. Pavlović D, Neville DC, Argaud O, Blumberg B, Dwek RA, Fischer WB, Zitzmann N. The hepatitis C virus p7 protein forms an ion channel that is inhibited by long-alkyl-chain iminosugar derivatives.. Proc Natl Acad Sci U S A 2003 May 13;100(10):6104-8.
    doi: 10.1073/pnas.1031527100pmc: PMC156333pubmed: 12719519google scholar: lookup
  55. Griffin S. "Too little, too late?" Will inhibitors of the hepatitis C virus p7 ion channel ever be used in the clinic?. Future Med Chem 2014;6(17):1893-907.
    doi: 10.4155/fmc.14.121pubmed: 25495983google scholar: lookup
  56. Carrère-Kremer S, Montpellier C, Lorenzo L, Brulin B, Cocquerel L, Belouzard S, Penin F, Dubuisson J. Regulation of hepatitis C virus polyprotein processing by signal peptidase involves structural determinants at the p7 sequence junctions.. J Biol Chem 2004 Oct 1;279(40):41384-92.
    doi: 10.1074/jbc.M406315200pubmed: 15247249google scholar: lookup
  57. Scull MA, Schneider WM, Flatley BR, Hayden R, Fung C, Jones CT, van de Belt M, Penin F, Rice CM. The N-terminal Helical Region of the Hepatitis C Virus p7 Ion Channel Protein Is Critical for Infectious Virus Production.. PLoS Pathog 2015 Nov;11(11):e1005297.
    doi: 10.1371/journal.ppat.1005297pmc: PMC4654572pubmed: 26588073google scholar: lookup
  58. StGelais C, Foster TL, Verow M, Atkins E, Fishwick CW, Rowlands D, Harris M, Griffin S. Determinants of hepatitis C virus p7 ion channel function and drug sensitivity identified in vitro.. J Virol 2009 Aug;83(16):7970-81.
    doi: 10.1128/JVI.00521-09pmc: PMC2715780pubmed: 19493992google scholar: lookup
  59. Sakai A, Claire MS, Faulk K, Govindarajan S, Emerson SU, Purcell RH, Bukh J. The p7 polypeptide of hepatitis C virus is critical for infectivity and contains functionally important genotype-specific sequences.. Proc Natl Acad Sci U S A 2003 Sep 30;100(20):11646-51.
    doi: 10.1073/pnas.1834545100pmc: PMC208812pubmed: 14504405google scholar: lookup
  60. Steinmann E, Whitfield T, Kallis S, Dwek RA, Zitzmann N, Pietschmann T, Bartenschlager R. Antiviral effects of amantadine and iminosugar derivatives against hepatitis C virus.. Hepatology 2007 Aug;46(2):330-8.
    pubmed: 17599777doi: 10.1002/hep.21686google scholar: lookup
  61. Crooks GE, Hon G, Chandonia JM, Brenner SE. WebLogo: a sequence logo generator.. Genome Res 2004 Jun;14(6):1188-90.
    doi: 10.1101/gr.849004pmc: PMC419797pubmed: 15173120google scholar: lookup
  62. von Heijne G. The signal peptide.. J Membr Biol 1990 May;115(3):195-201.
    doi: 10.1007/BF01868635pubmed: 2197415google scholar: lookup
  63. von Heijne G. Life and death of a signal peptide.. Nature 1998 Nov 12;396(6707):111, 113.
    doi: 10.1038/24036pubmed: 9823886google scholar: lookup

Citations

This article has been cited 4 times.
  1. Boukadida C, Fritz M, Blumen B, Fogeron ML, Penin F, Martin A. NS2 proteases from hepatitis C virus and related hepaciviruses share composite active sites and previously unrecognized intrinsic proteolytic activities. PLoS Pathog 2018 Feb;14(2):e1006863.
    doi: 10.1371/journal.ppat.1006863pubmed: 29415072google scholar: lookup
  2. Tanaka T, Otoguro T, Yamashita A, Kasai H, Fukuhara T, Matsuura Y, Moriishi K. Roles of the 5' Untranslated Region of Nonprimate Hepacivirus in Translation Initiation and Viral Replication. J Virol 2018 Apr 1;92(7).
    doi: 10.1128/JVI.01997-17pubmed: 29343570google scholar: lookup
  3. Pfaender S, Walter S, Grabski E, Todt D, Bruening J, Romero-Brey I, Gather T, Brown RJ, Hahn K, Puff C, Pfankuche VM, Hansmann F, Postel A, Becher P, Thiel V, Kalinke U, Wagner B, Bartenschlager R, Baumgärtner W, Feige K, Pietschmann T, Cavalleri JM, Steinmann E. Immune protection against reinfection with nonprimate hepacivirus. Proc Natl Acad Sci U S A 2017 Mar 21;114(12):E2430-E2439.
    doi: 10.1073/pnas.1619380114pubmed: 28275093google scholar: lookup
  4. Brown E, Swinscoe G, Lefteri DA, Singh R, Moran A, Thompson RF, Maskell D, Beaumont H, Bentham MJ, Donald C, Kohl A, Macdonald A, Ranson N, Foster R, McKimmie CS, Kalli AC, Griffin S. Inhibitors of the small membrane (M) protein viroporin prevent Zika virus infection. Elife 2024 Aug 23;13.
    doi: 10.7554/eLife.68404pubmed: 39177307google scholar: lookup
Subscribe to our newsletter
Join 99,970 horse owners like you who receive our email updates on horse health and nutrition.