title: Superinfection exclusion in cells infected with hepatitis C virus.
abstract: Superinfection exclusion is the ability of an established virus infection to interfere with infection by a second virus. In this study, we found that Huh-7.5 cells acutely infected with hepatitis C virus (HCV) genotype 2a (chimeric strain J6/JFH) and cells harboring HCV genotype 1a, 1b, or 2a full-length or subgenomic replicons were resistant to infection with cell culture-produced HCV (HCVcc). Replicon-containing cells became permissive for HCVcc infection after treatment with an HCV-specific protease inhibitor. With the exception of cells harboring a J6/JFH-FLneo replicon, infected or replicon-containing cells were permissive for HCV pseudoparticle (HCVpp) entry, demonstrating a postentry superinfection block downstream of primary translation. The surprising resistance of J6/JFH-FLneo replicon-containing cells to HCVpp infection suggested a defect in virus entry. This block was due to reduced expression of the HCV coreceptor CD81. Further analyses indicated that J6/JFH may be toxic for cells expressing high levels of CD81, thus selecting for a CD81(low) population. CD81 down regulation was not observed in acutely infected cells, suggesting that this may not be a general mechanism of HCV superinfection exclusion. Thus, HCV establishes superinfection exclusion at a postentry step, and this effect is reversible by treatment of infected cells with antiviral compounds.
authors.affiliation: Laboratory of Virology and Infectious Diseases, Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Tscherne
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Evans
authors.forename: Thomas
authors.initials: T
authors.lastname: von Hahn
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Jones
authors.forename: Zania
authors.initials: Z
authors.lastname: Stamataki
authors.forename: Jane A
authors.initials: JA
authors.lastname: McKeating
authors.forename: Brett D
authors.initials: BD
authors.lastname: Lindenbach
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rice
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis; D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D011480:Protease Inhibitors / Q000494:pharmacology; D011991:Receptors, Virus / Q000096:biosynthesis; D012093:Replicon; D060225:Tetraspanin 28; D014762:Viral Interference; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D015703:Antigens, CD; D000998:Antiviral Agents; C554798:CD81 protein, human; D011480:Protease Inhibitors; D011991:Receptors, Virus; D060225:Tetraspanin 28