Impaired antiviral response in human hepatoma cells

Hepatitis B, C, and D viruses can infect liver cells and in some individual s establish a chronic phase of infection. Presently, relatively little info rmation is available on the antiviral mechanisms in liver cells. Because no good in vitro model infection systems for hepatitis viruses are available, we have used influenza A, Sendal, and vesicular stomatitis (VSV) viruses t o characterize interferon (IFN) responses and IFN-induced antiviral mechani sms in human hepatoma cell lines. HepG2 or HuH7 cells dib not show any dete ctable IFN-alpha/beta production in response to influenza A or Sendal virus infections. Treatment of cells with IFN-alpha resulted in upregulation of IFN-alpha-inducible Mx, 2',5'-oligoadenylate synthetase (OAS) and HLA class I gene expression but only with exceptionally high levels of IFN-alpha (gr eater than or equal to 100 IU/ml). Accordingly, high pretreatment levels of IFN-alpha, 1000 IU/ml for influenza A end VSV and 100 IU/ml for Sendai vir us, were required before any detectable antiviral activity against these vi ruses was seen. IFN-gamma had some antiviral effect against influenza A vir us but appeared to be ineffective against VSV and Sendai virus. IFN-gamma u pregulated HLA class I protein expression, whereas Mx or OAS expression lev els were not increased. There was a modest upregulation of HLA class I expr ession during Sendai virus infection, whereas influenza A virus infection r esulted, after an initial weak upregulation, in a clear decrease in HLA cla ss I expression at late times of infection. The results suggest that hepato ma cells may have intrinsically poor ability to produce and respond to type I IFNs, which may contribute to their inability to efficiency resist viral infections. (C) 1999 Academic Press.