Timed appearance of lymphocytic choriomeningitis virus after gastric inoculation of mice.

Arenaviruses present an emerging health threat in agrarian areas of Africa and South America; however, the natural routes of arenaviral infections are not clearly understood. Our previous studies with lymphocytic choriomeningitis virus (LCMV), the prototype arenavirus, implicate oral and intragastric routes as natural routes of infection. Our studies raised many questions about the primary site of infection and the route of dissemination after gastric infection. In this report, we use in situ hybridization to detect LCMV in various organs at different time points (0 to 96 hours). After gastric inoculation, the gastric mucosa is the initial site of viral infection, followed by infection of the spleen and liver, then ileum and last, lung, kidney, brain, and esophagus. Furthermore, our observations suggest that virus is disseminated lymphatically rather than by a hematogenous route. Infectious center assays using mononuclear cells from stomach, blood, and spleen of mice infected by the gastric route confirmed active infection with LCMV and the presence of mononuclear cells producing infectious virus in these tissues. This is the first identification of gastric epithelia as a primary site of virus infection.