Abstract
The pathogenesis for adult rats of a Venezuelan encephalitis virus (VEE) strain, V‐198, was studied. This virus strain was chosen following virulence‐testing of 12 prototype alphavirus strains, selected from the Semliki Forest, Venezuelan, Eastern, and Western encephalitis virus complexes; only VEE strain V‐198 killed all adult rats when inoculated subcutaneously (sc) with 6.0–6.5 log~10~ plaque‐forming units (PFU). Lower doses of strain V‐198 by the same route were also lethal: 5.0 and 3.0 log~10~ PFU killed 100%, and 1.0 log~10~ PFU killed 70% of rats. Viral infectivity titrations of tissues obtained from V‐198 straininfected rats demonstrated that virus replicated early in thymus and spleen, but did not replicate in bone marrow or liver. Following a brief viremia, virus infectivity titers peaked in brain, but did not persist there. A biphasic neutrophilia also occurred. Lower doses of inoculum virus affected the timing but not the degree of neutrophil fluctuations, virus replication, and clinical disease. Rats, moribund seven days after inoculation of 4.3 log~10~ PFU, exhibited central nervous system signs and histologic evidence of encephalomyelitis. Significant proportions of rats, otherwise lethally infected with V‐198 virus, were protected by a single intraperitoneal inoculation of hyperimmune V‐198 antiserum, administered 3 or 4, but not 5 days after virus.
Since the rat has been well characterized with respect to metabolic alterations following other infectious diseases, it is anticipated that this model for lethal virus‐induced disease will be useful for defining more precisely the functional relationships between viral growth, tissue destruction, metabolic alterations, and clinical course of disease, and that it may suggest specific approaches for effective treatment of viral diseases in general.