Infection of cultured murine brain cells by Semliki Forest virus: effects of interferon-alpha beta on viral replication, viral antigen display, major histocompatibility complex antigen display and lysis by cytotoxic T lymphocytes.
Primary brain cell cultures prepared from newborn mice were infected with Semliki Forest virus (SFV). The effects of interferon (IFN-alpha beta) treatment on SFV replication, SFV and major histocompatibility complex (MHC) class I antigen expression, and susceptibility to lysis by SFV-specific cytotoxic T lymphocytes (CTL) were determined. The IFN-alpha beta treatment prevented replication of SFV as determined by incorporation of [3H]uridine into SFV RNA and very markedly reduced the expression of SFV antigens on the cell surface as determined by lysis with antibody and complement or indirect immunofluorescence. However, IFN-alpha beta increased expression of MHC class I antigens, measured by indirect immunofluorescence and as assessed indirectly by susceptibility to killing by alloreactive T cell lines. SFV infection had no effect on MHC class I expression in either IFN-alpha beta-treated or -untreated cells. The infected IFN-alpha beta-untreated brain cells were susceptible to killing by the CTL at effector/target ratios in the range 3 to 30. The killing was MHC antigen-restricted, and uninfected cells were not killed. A target cell (YAC) highly susceptible to natural killer cell cytotoxicity was not killed by the CTL. IFN-alpha beta treatment prior to SFV infection resulted in an augmentation of lysis by the CTL, indicating that even where SFV antigen expression is reduced, in the context of enhanced MHC class I expression brain cells remain susceptible to CTL killing.
D000818:Animals; D000831:Animals, Newborn; D000956:Antigens, Viral / Q000032:analysis; D001921:Brain / Q000276:immunology / Q000382:microbiology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004261:DNA Replication / Q000187:drug effects*; D007370:Interferon Type I / Q000494:pharmacology*; D008285:Major Histocompatibility Complex; D051379:Mice; D008809:Mice, Inbred C3H; D012672:Semliki forest virus / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014779:Virus Replication / Q000187:drug effects
D000956:Antigens, Viral; D007370:Interferon Type I