Evolution of lymphocytic choriomeningitis virus infection from neonatal inoculation through development of adult “late onset disease” and glomerulonephritis

Summary

Immunofluorescent studies of infection following intracerebral inoculation of LCM virus in neonatal mice show that virus spreads by contamination of cerebrospinal fluid and subcutaneous connective tissue, in addition to invasion of the bloodstream. Hematogenous dissemination involves the liver in 1 day, the spleen and kidneys in 2 days, and all remaining organs and tissues of the body, including the entire lymphoreticular system, in 3 days, with stability of the infection reached in 5 days. Hematogenous spread probably occurs via freely circulating plasma virus, since no virus is seen in red cells, and infected white cells appear only after the earliest peripheral tissue infection has already occurred.

Fluorescence in organs of older mice afflicted with “late disease” remains intense, and is indistinguishable in distribution from that seen in neonatal tolerant mice. Heaviest infection, occurring in the skin, gastrointestinal tract, and kidneys, explains the high degree of contagiousness noted in such animals, and may also be relevant to the pathogenesis of “late disease”, characterized by sparse and ruffled fur, weight loss, and glomerulonephritis. In particular, persistent viral proliferation in the kidneys may contribute to the virus-gamma globulin complexes coating and perhaps damaging the glomeruli.