دورية أكاديمية
Characterization of virus‒host recombinant variants of the hepatitis E virus.
| العنوان: | Characterization of virus‒host recombinant variants of the hepatitis E virus. |
|---|---|
| المؤلفون: | Paronetto O; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), UMR 5051 (CNRS), UMR 1291 (INSERM), Université Toulouse III-Paul Sabatier, Toulouse, France., Allioux C; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), UMR 5051 (CNRS), UMR 1291 (INSERM), Université Toulouse III-Paul Sabatier, Toulouse, France., Diméglio C; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), UMR 5051 (CNRS), UMR 1291 (INSERM), Université Toulouse III-Paul Sabatier, Toulouse, France.; Laboratoire de Virologie, Hôpital Purpan, CHU Toulouse, Toulouse, France., Lobjois L; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), UMR 5051 (CNRS), UMR 1291 (INSERM), Université Toulouse III-Paul Sabatier, Toulouse, France., Jeanne N; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), UMR 5051 (CNRS), UMR 1291 (INSERM), Université Toulouse III-Paul Sabatier, Toulouse, France.; Laboratoire de Virologie, Hôpital Purpan, CHU Toulouse, Toulouse, France., Ranger N; Laboratoire de Virologie, Hôpital Purpan, CHU Toulouse, Toulouse, France., Boineau J; Laboratoire de Virologie, Hôpital Purpan, CHU Toulouse, Toulouse, France., Pucelle M; Laboratoire de Virologie, Hôpital Purpan, CHU Toulouse, Toulouse, France., Demmou S; Laboratoire de Virologie, Hôpital Purpan, CHU Toulouse, Toulouse, France., Abravanel F; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), UMR 5051 (CNRS), UMR 1291 (INSERM), Université Toulouse III-Paul Sabatier, Toulouse, France.; Laboratoire de Virologie, Hôpital Purpan, CHU Toulouse, Toulouse, France., Chapuy-Regaud S; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), UMR 5051 (CNRS), UMR 1291 (INSERM), Université Toulouse III-Paul Sabatier, Toulouse, France.; Laboratoire de Virologie, Hôpital Purpan, CHU Toulouse, Toulouse, France., Izopet J; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), UMR 5051 (CNRS), UMR 1291 (INSERM), Université Toulouse III-Paul Sabatier, Toulouse, France.; Laboratoire de Virologie, Hôpital Purpan, CHU Toulouse, Toulouse, France., Lhomme S; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), UMR 5051 (CNRS), UMR 1291 (INSERM), Université Toulouse III-Paul Sabatier, Toulouse, France.; Laboratoire de Virologie, Hôpital Purpan, CHU Toulouse, Toulouse, France. |
| المصدر: | Journal of virology [J Virol] 2024 Jun 13; Vol. 98 (6), pp. e0029524. Date of Electronic Publication: 2024 May 07. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0113724 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-5514 (Electronic) Linking ISSN: 0022538X NLM ISO Abbreviation: J Virol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington Dc : American Society For Microbiology Original Publication: Baltimore, American Society for Microbiology. |
| مواضيع طبية MeSH: | Hepatitis E virus*/classification , Hepatitis E virus*/drug effects , Hepatitis E virus*/genetics , Hepatitis E virus*/growth & development , Recombination, Genetic* , Host Microbial Interactions*/genetics, Humans ; Antiviral Agents/pharmacology ; Hep G2 Cells ; Hepatitis E/genetics ; Hepatitis E/virology ; Protein Processing, Post-Translational ; Ribavirin/pharmacology ; RNA, Viral/genetics ; RNA, Viral/metabolism ; Virus Replication/drug effects ; Virus Replication/genetics ; Ubiquitination/genetics ; Plasmids/genetics |
| مستخلص: | Hepatitis E virus is a single-strand, positive-sense RNA virus that can lead to chronic infection in immunocompromised patients. Virus-host recombinant variants (VHRVs) have been described in such patients. These variants integrate part of human genes into the polyproline-rich region that could introduce new post-translational modifications (PTMs), such as ubiquitination. The aim of this study was to characterize the replication capacity of different VHRVs, namely, RNF19A, ZNF787, KIF1B, EEF1A1, RNA18, RPS17, and RPL6. We used a plasmid encoding the Kernow strain, in which the fragment encoding the S17 insertion was deleted (Kernow p6 delS17) or replaced by fragments encoding the different insertions. The HEV RNA concentrations in the supernatants and the HepG2/C3A cell lysates were determined via RT-qPCR. The capsid protein ORF2 was immunostained. The effect of ribavirin was also assessed. The HEV RNA concentrations in the supernatants and the cell lysates were higher for the variants harboring the RNF19A, ZNF787, KIF1B, RPS17, and EEF1A1 insertions than for the Kernow p6 del S17, while it was not with RNA18 or RPL6 fragments. The number of ORF2 foci was higher for RNF19A, ZNF787, KIF1B, and RPS17 than for Kernow p6 del S17. VHRVs with replicative advantages were less sensitive to the antiviral effect of ribavirin. No difference in PTMs was found between VHRVs with a replicative advantage and those without. In conclusion, our study showed that insertions did not systematically confer a replicative advantage in vitro . Further studies are needed to determine the mechanisms underlying the differences in replicative capacity. Importance: Hepatitis E virus (HEV) is a major cause of viral hepatitis. HEV can lead to chronic infection in immunocompromised patients. Ribavirin treatment is currently used to treat such chronic infections. Recently, seven virus-host recombinant viruses were characterized in immunocompromised patients. These viruses have incorporated a portion of a human gene fragment into their genome. We studied the consequences of these insertions on the replication capacity. We found that these inserted fragments could enhance virus replication for five of the seven recombinant variants. We also showed that the recombinant variants with replicative advantages were less sensitive to ribavirin in vitro . Finally, we found that the mechanisms leading to such a replicative advantage do not seem to rely on the post-translational modifications introduced by the human gene fragment that could have modified the function of the viral protein. The mechanisms involved in improving the replication of such recombinant viruses remain to be explored. Competing Interests: The authors declare no conflict of interest. |
| References: | N Engl J Med. 2014 Mar 20;370(12):1111-20. (PMID: 24645943) J Hepatol. 2018 Jun;68(6):1256-1271. (PMID: 29609832) Front Microbiol. 2021 Jul 16;12:696680. (PMID: 34335528) J Gen Virol. 2020 Jul;101(7):692-698. (PMID: 32469300) Front Microbiol. 2020 Jun 16;11:1156. (PMID: 32612582) Virology. 2023 Jan;578:128-140. (PMID: 36527931) J Virol. 1999 Jul;73(7):5646-53. (PMID: 10364314) Gastroenterology. 2018 Jan;154(1):211-223.e8. (PMID: 28958858) Antimicrob Agents Chemother. 2015 Dec 28;60(3):1608-14. (PMID: 26711757) J Hepatol. 2016 Sep;65(3):499-508. (PMID: 27174035) Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2438-43. (PMID: 21262830) Am J Transplant. 2013 Jul;13(7):1935-6. (PMID: 23659713) Cold Spring Harb Perspect Med. 2019 Jan 2;9(1):. (PMID: 29530948) J Clin Microbiol. 2012 Mar;50(3):897-902. (PMID: 22205792) J Virol. 2014 Oct;88(20):12098-111. (PMID: 25122776) Viruses. 2022 Jul 14;14(7):. (PMID: 35891516) Proc Natl Acad Sci U S A. 2017 Sep 5;114(36):E7489-E7498. (PMID: 28827361) Sci Rep. 2022 Feb 2;12(1):1720. (PMID: 35110582) Am J Transplant. 2008 Aug;8(8):1744-8. (PMID: 18557740) Virology. 2001 Dec 5;291(1):77-90. (PMID: 11878878) J Clin Med. 2020 Jan 24;9(2):. (PMID: 31991629) Nat Rev Dis Primers. 2017 Nov 16;3:17086. (PMID: 29154369) Biol Direct. 2015 Apr 11;10:16. (PMID: 25886938) Trends Microbiol. 2014 Feb;22(2):59-64. (PMID: 24268716) J Clin Virol. 2016 Jun;79:1-5. (PMID: 27038538) Biochimie. 2017 Oct;141:70-79. (PMID: 28483690) PLoS Pathog. 2017 May 30;13(5):e1006417. (PMID: 28558073) Liver Int. 2023 Apr;43(4):794-804. (PMID: 36617681) Sci Rep. 2019 Apr 18;9(1):6243. (PMID: 31000788) J Virol. 2015 Apr;89(7):3793-803. (PMID: 25609799) N Engl J Med. 2008 Feb 21;358(8):859-60. (PMID: 18287615) J Virol. 2012 May;86(10):5697-707. (PMID: 22398290) Front Microbiol. 2020 Jan 31;11:1. (PMID: 32082274) N Engl J Med. 2008 Feb 21;358(8):811-7. (PMID: 18287603) PLoS Pathog. 2018 Dec 10;14(12):e1007471. (PMID: 30532200) J Virol. 2016 Apr 14;90(9):4394-401. (PMID: 26889028) Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):1147-1152. (PMID: 28096411) J Viral Hepat. 2014 Jun;21(6):447-56. (PMID: 24750215) J Virol. 2014 Oct;88(20):12017-25. (PMID: 25100839) J Gen Virol. 2012 Mar;93(Pt 3):526-530. (PMID: 22113007) Proc Natl Acad Sci U S A. 2018 May 1;115(18):4773-4778. (PMID: 29669922) Clin Infect Dis. 2020 Aug 22;71(5):1204-1211. (PMID: 31793638) Gut. 2020 May;69(5):901-910. (PMID: 31727684) Viruses. 2019 May 17;11(5):. (PMID: 31108942) PLoS Pathog. 2022 Aug 25;18(8):e1010798. (PMID: 36007070) |
| معلومات مُعتمدة: | ECTZ159924 Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS); ECTZ189528 Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS) |
| فهرسة مساهمة: | Keywords: hepatitis E virus; ribavirin; viral fitness; virus–host recombinant variants |
| المشرفين على المادة: | 0 (Antiviral Agents) 49717AWG6K (Ribavirin) 0 (RNA, Viral) 0 (ORF2 protein, Hepatitis E virus) |
| تواريخ الأحداث: | Date Created: 20240507 Date Completed: 20240613 Latest Revision: 20240716 |
| رمز التحديث: | 20240717 |
| مُعرف محوري في PubMed: | PMC11237545 |
| DOI: | 10.1128/jvi.00295-24 |
| PMID: | 38712945 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1098-5514 |
|---|---|
| DOI: | 10.1128/jvi.00295-24 |