Superinfection exclusion in cells infected with hepatitis C virus

J Virol. 2007 Apr;81(8):3693-703. doi: 10.1128/JVI.01748-06. Epub 2007 Feb 7.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / biosynthesis
  • Antiviral Agents / pharmacology
  • Cell Line
  • Hepacivirus / physiology*
  • Humans
  • Protease Inhibitors / pharmacology
  • Receptors, Virus / biosynthesis
  • Replicon
  • Tetraspanin 28
  • Viral Interference*
  • Virus Internalization
  • Virus Replication


  • Antigens, CD
  • Antiviral Agents
  • CD81 protein, human
  • Protease Inhibitors
  • Receptors, Virus
  • Tetraspanin 28