Subacute Infection with Temperature-Sensitive Vesicular Stomatitis Virus Mutant G41 in the Central Nervous System of Mice. I. Clinical and Virologic Studies

Abstract

Inoculation of three- to four-week-old BALB/c mice with temperature-sensitive (ts) vesicular stomatitis virus mutant G41 produced a subacute neurological disease, initially characterized by development of lethargy, hunched posture, and ruffled fur within five to seven days after infection. More than 90% of infected mice developed these clinical signs. In approximately 60% of infected mice, the initial neurological signs proceeded to striking hind-limb paralysis and weight loss. These signs usually appeared by seven to nine days after infection and lasted for 21-28 days. Only 16% of the mice died as a result of infection; death usually occurred eight to 12 days after infection. Most of the infected mice recovered from the acute phase of disease and appeared normal by four weeks after infection. However, hind-limb paralysis persisted in 4% of the mice for as long as the mice were observed, i.e., 42 days. The mutant ts-G41 was recovered from the brains and spinal cords of infected mice for the first seven days after infection. Peak titers of virus were modest, 10(4)-10(5) pfu/ml in brain tissue and 10(3)-10(4) pfu/ml in spinal cord tissue. Virus isolated after in vivo infection was temperature-sensitive and thus not revertant wild-type virus. Although virus was recoverable by homogenization for only the first seven days of infection, use of cocultivation techniques permitted the detection of ts-G41 in brains and spinal cords of infected animals for as long as 21 days after infection. Virus recovered by cocultivation was also temperature-sensitive.