Major histocompatibility complex-linked susceptibility or resistance to disease caused by a noncytopathic virus varies with the disease parameter evaluated.

Abstract

The influence of major transplantation antigens on susceptibility to T cell-mediated disease caused by infection with the noncytopathic virus lymphocytic choriomeningitis virus (LCMV) was evaluated in B10 H-2-congenic mice. Susceptibility to early T cell-mediated liver cell destruction (day 7-9) and early mortality (before day 12) was H-2Dq linked and correlated directly with early (day 6-8) and high cytotoxic T cell activity. In contrast, susceptibility to become an LCMV carrier, inability to rapidly clear virus, or tendency to develop late hepatitis (day 14-17) was linked to Dk and correlated with absence of early cytotoxic T cell activity. Thus, H-2D-regulated T cell-immune responses controlling both virus spread and immunopathology may directly determine the type and severity of disease. The results illustrate that susceptibility to disease caused by one virus may be linked to distinct MHC alleles dependent upon the disease parameter studied.

Hypercholesterolemia Exacerbates Virus-Induced Immunopathologic Liver Disease Via Suppression of Antiviral Cytotoxic T Cell Responses

“…The importance of CTL in LCMV-induced immunopathology also has been demonstrated in transgenic mice expressing the LCMV glycoprotein in the islets of Langerhans (16,17) where contact-dependent, perforin-mediated lysis of viral Ag-expressing cells is crucial to mediate the immunopathologic response (18). The extent of LCMV-induced immunopathologic disease depends on various host and virus parameters, such as viral tropism (14,19), genetic background (19,20), and immunocompetence of the host (21).…”

“…We used here ApoE Ϫ/Ϫ and LDLR Ϫ/Ϫ mice to determine whether these factors alter virushost equilibrium and enhance or prevent immunopathologic disease. Mice were infected with the hepatotropic LCMV WE strain, which can lead to substantial CTL-mediated liver cell damage in a dose-, age-, and MHC-dependent fashion (14,20). Using MHC class I tetramers complexed with defined viral epitopes (22, 23), we followed activation and peripheral recruitment of virus-specific CTL.…”

The Susceptibility to Cytotoxic T Lymphocyte Mediated Lysis of Chemically Induced Sarcomas from Immunodeficient and Normal Mice

“…The LCM virus used is rather promiscuous in its choice of target cells due to the fact that no virus receptor is needed, and a large number of different cell types including normal fibroblasts and MCA induced fibrosarcoma cell lines have been shown to be susceptible to infection [22,[30][31][32]. Therefore, the wide variation among the tumours in their ability to process and present the viral antigen is unlikely to be caused by differences in their susceptibility to infection with LCMV.…”

Host factors influencing viral persistence

“…This is very important since with non-cytocidal viruses this is the factor that determines the life or death of the infected host. An apparant paradox in this context is the observation that a partial immune defect may sometimes be associated with augmented immunopathology (see Marker et al 1976;Leist et al 1989). The reason for this becomes obvious when considering that a weakening of the T-cell response not only reduces the capacity to induce tissue damage, but also impairs antiviral e¡ector capacity.…”

“…This statement is self-evident for infecting agents with the capacity to seriously disturb host organ functions, but even in the case of, for example, non-cytocidal viruses, this may be very important. Thus, if too many host cells in critical organ sites have become infected before an e¤cient immune attack is established, the host may succumb from its own attempt to clear the infection (see, for example, Marker et al 1976; Thomsen et al 1979;Leist et al 1989;Ehl et al 1998). In this context, it should be remembered that non-cytocidal viruses may replicate to high titres without seriously a¡ecting the hostöthus allowing the stage to be set for the above scenario.…”