Comparative pathology of Lassa virus infection in monkeys, guinea pigs, and Mastomys natalensis

Experimental Lassa virus infections of squirrel monkeys, guinea pigs, and the African multimammate rat, Mastomys natalensis, were studied virologically and pathologically. In the monkeys, early viral lymphoreticulotropism, hepatotropism, nephrotropism, and viremia were noted. At the time of death, viral titers in nearly all target organs were associated with necrotic changes: splenic lymphoid necrosis, renal tubular necrosis, myocarditis, arteritis, and hepatocytic regeneration. In convalescent monkeys, organ titres diminished slowly, and viraemia persisted at 28 days. At this time, renal and splenic regeneration was occurring and a new lesion, choriomeningitis, was present. Guinea pigs infected with Lassa virus developed respiratory insufficiency with pulmonary edema, alveolar hyaline membranes, myocarditis, and focal calcification of myocardial fibers and hepatocytes. Dying animals contained Lassa virus in virtually every organ tested, whereas survivors at 56 days were free of virus and had high complement fixing antibody titers. Infection of neonatal Mastomys did not cause any clinical disease or pathologic lesions despite the presence of virus in the blood, lymph nodes, liver, spleen, lung, brain, urine, and throat secretions throughout the 74 day study. Infected adult Mastomys also remained normal but had virus in many organs. In one animal, virus persisted until the termination of the study at 103 days. Several animals developed a mild meningoencephalitis. The pattern of infection and virus shedding in M. natalensis is ideal for maintenance of the virus in nature; together with the epidemiologic field data this emphasizes the incidental nature of the exposure and infection of man.