Infection of Cultured Murine Brain Cells by Semliki Forest Virus: Effects of Interferon- beta on Viral Replication, Viral Antigen Display, Major Histocompatibility Complex Antigen Display and Lysis by Cytotoxic T Lymphocytes

Publisher Website
Google Scholar
Abstract
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.b-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 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.