Natural non-homologous recombination led to the emergence of a duplicated V3-NS5A region in HCV-1b strains associated with hepatocellular carcinoma - Groupe VIH et Virus Humains Persistants / HIV and Human Persistent Virus Group (IBS-HIV&HPV) Access content directly
Journal Articles PLoS ONE Year : 2017

Natural non-homologous recombination led to the emergence of a duplicated V3-NS5A region in HCV-1b strains associated with hepatocellular carcinoma

1 HIFIH - Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques
2 CHU Angers - Centre Hospitalier Universitaire d'Angers
3 CHU Clermont-Ferrand
4 LMGE - Laboratoire Microorganismes : Génome et Environnement
5 LUBEM - Laboratoire Universitaire de Biodiversité et Ecologie Microbienne
6 Service de Bactériologie, Virologie, Hygiène [CHU Limoges]
7 RESINFIT - Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques
8 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
9 CPTP - Centre de Physiopathologie Toulouse Purpan
10 EA 4474 - Virologie de l'hépatite C
11 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
12 Hôpital Cochin [AP-HP]
13 UPD5 - Université Paris Descartes - Paris 5
14 Hôtel-Dieu de Nantes
15 Laboratoire de sérologie-virologie (CHU de Dijon)
16 Service de bactériologie-Virologie-Hygiène [Avicenne]
17 Service de virologie et d'immunologie biologique
18 Hôpital de la Croix-Rousse [CHU - HCL]
19 MAVIVHe - Morphogénèse et antigénicité du VIH, des Virus des Hépatites et Emergents
20 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
21 UGA UFRP - Université Grenoble Alpes - UFR Pharmacie
22 IBS - UMR 5075 - Institut de biologie structurale
23 GIMAP - Groupe Immunité des Muqueuses et Agents Pathogènes
24 Interaction virus-hôte et maladies du foie
25 IMRB - Institut Mondor de Recherche Biomédicale
26 IRHS - Institut de Recherche en Horticulture et Semences
Adeline Pivert
  • Function : Author
  • PersonId : 992791
Patrice André
Jacques Izopet

Abstract

Background: The emergence of new strains in RNA viruses is mainly due to mutations or intra and inter-genotype homologous recombination. Non-homologous recombinations may be deleterious and are rarely detected. In previous studies, we identified HCV-1b strains bearing two tandemly repeated V3 regions in the NS5A gene without ORF disruption. This polymorphism may be associated with an unfavorable course of liver disease and possibly involved in liver carcinogenesis. Here we aimed at characterizing the origin of these mutant strains and identifying the evolutionary mechanism on which the V3 duplication relies. Methods: Direct sequencing of the entire NS5A and E1 genes was performed on 27 mutant strains. Quasispecies analyses in consecutive samples were also performed by cloning and sequencing the NS5A gene for all mutant and wild strains. We analyzed the mutant and wild-type sequence polymorphisms using Bayesian methods to infer the evolutionary history of and the molecular mechanism leading to the duplication-like event. Results: Quasispecies were entirely composed of exclusively mutant or wild-type strains respectively. Mutant quasispecies were found to have been present since contamination and had persisted for at least 10 years. This V3 duplication-like event appears to have resulted from non-homologous recombination between HCV-1b wild-type strains around 100 years ago. The association between increased liver disease severity and these HCV-1b mutants may explain their persistence in chronically infected patients. Conclusions: These results emphasize the possible consequences of non-homologous recombination in the emergence and severity of new viral diseases.

Domains

Virology
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Dates and versions

hal-01882310 , version 1 (26-09-2018)

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Hélène Le Guillou-Guillemette, Adeline Pivert, Elise Bouthry, Cécile Henquell, Odile Petsaris, et al.. Natural non-homologous recombination led to the emergence of a duplicated V3-NS5A region in HCV-1b strains associated with hepatocellular carcinoma. PLoS ONE, 2017, 12 (4), pp.e0174651. ⟨10.1371/journal.pone.0174651⟩. ⟨hal-01882310⟩
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