LCM Virus Infection and Nephritis

Abstract

Lymphocytic choriomeningitis (LCM) virus was first described in the mid- 1980s by Traub (1939) who noted that serum from certain mice was lethal when injected intracerebrally into other strains of mice. He demonstrated that the lethal agent was a vertically transmitted virus. Based on Traub’s early work, chronic LCM virus infection was felt to be the result of host immunological tolerance to the virus (Burnet and Fenner, 1949). In the mid- 1950s, Rowe (1954) demonstrated that LCM virus was not intrinsically cytopathic, i.e., the lethal acute meningitis following intracerebral injection of adult immunocompetent mice resulted from the animal’s immune reaction to the virus. While chronic LCM virus infection was long thought to result in no disease, Hotchin and Collins (1964) noted the occurrence of “late onset disease” with glomerulonephritis in persistently infected mice. Oldstone and Dixon (1967) demonstrated that the glomerulonephritis in mice with chronic LCM virus infection had an immune complex pathogenesis, They performed studies of the immunoglobulin eluted from the kidneys of chronically infected mice and reported that the eluted antibody had binding specificity for LCM antigens. This latter observation implied that mice chronically infected with LCM virus were not immunologically tolerant to the virus as had been previously thought (Burnet and Fenner, 1949). Controversy over this observation has continued and will be addressed later in this chapter.