Introduction
Lymphocytic choriomeningitis virus (LCMV) causes a natural infection in mice and provides a useful model for studying the interaction between a viral infection and host immunity. First isolated in the 1930s by Armstrong and Lillie [4], LCMV derived its name from the acute central nervous (CNS) system disease that occurred after intracerebral inoculation of virus into mice and monkeys. Subsequent work revealed, however, that LCMV itself was noncytocidal, and that the characteristic choriomeningirls was a manifestation of the host immune response to the virus. In other diseases resulting from LCMV infection, such as hepatitis and immune-complex disease, the pathological basis for disease is also immune mediated. Studies of this early model of immune-mediated viral disease provided the groundwork for our recognition and understanding of viral immunopathology. In this chapter, we will review the immunology of LCMV infection, focusing on the immunopathology of LCMV disease and the possible mechanisms involved.
The immune response to LCMV
Intravenous or intraperitoneal injection of adult immunocompetent mice with the Armstrong strain of LCMV results in an acute infection. Following infection, the virus replicates rapidly in many tissues such as the lung, liver, spleen and lymph nodes. Levels of infectious virus peak approximately 3 days after infection. By day 5, there is a rapid decline in virus titers and the infection is almost completely resolved by day 8. Evaluation of the immune response shows that natural killer cell activity increases soon after infection and peaks at approximately day 3 [66]. Around day 5, LCMV-specific cytotoxic T cells (CTL) appear. The peak of the CTL response occurs at days 8-9 of infection and falls off rapidly over the next 5-10 days. Synthesis of