Determinants Involved in Hepatitis C Virus and GB Virus B Primate Host Restriction - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Virology Année : 2015

Determinants Involved in Hepatitis C Virus and GB Virus B Primate Host Restriction

Robert E Lanford
  • Fonction : Auteur
Nicola J Rose
  • Fonction : Auteur

Résumé

Hepatitis C virus (HCV) only infects humans and chimpanzees, while GB virus B (GBV-B), another hepatotropic hepacivirus, infects small New World primates (tamarins and marmosets). In an effort to develop an immunocompetent small primate model for HCV infection to study HCV pathogenesis and vaccine approaches, we investigated the HCV life cycle step(s) that may be restricted in small primate hepatocytes. First, we found that replication-competent, genome-length chimeric HCV RNAs encoding GBV-B structural proteins in place of equivalent HCV sequences designed to allow entry into simian hepatocytes failed to induce viremia in tamarins following intrahepatic inoculation, nor did they lead to progeny virus in permissive, transfected human Huh7.5 hepatoma cells upon serial passage. This likely reflected the disruption of interactions between distantly related structural and nonstructural proteins that are essential for virion production, whereas such cross talk could be restored in similarly designed HCV intergenotypic recombinants via adaptive mutations in NS3 protease or helicase domains. Next, HCV entry into small primate hepatocytes was examined directly using HCV-pseudotyped retroviral particles (HCV-pp). HCV-pp efficiently infected tamarin hepatic cell lines and primary marmoset hepatocyte cultures through the use of the simian CD81 ortholog as a coreceptor, indicating that HCV entry is not restricted in small New World primate hepatocytes. Furthermore, we observed genomic replication and modest virus secretion following infection of primary marmoset hepatocyte cultures with a highly cell culture-adapted HCV strain. Thus, HCV can successfully complete its life cycle in primary simian hepatocytes, suggesting the possibility of adapting some HCV strains to small primate hosts.
Fichier principal
Vignette du fichier
2015 Marnata et al J Virol.pdf (2.28 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-04631765 , version 1 (02-07-2024)

Identifiants

Citer

Caroline Marnata, Aure Saulnier, Dimitri Mompelat, Thomas Krey, Lisette Cohen, et al.. Determinants Involved in Hepatitis C Virus and GB Virus B Primate Host Restriction. Journal of Virology, 2015, 89 (23), pp.12131-12144. ⟨10.1128/jvi.01161-15⟩. ⟨hal-04631765⟩
0 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More