Infection and disease induced in chimpanzees with 6/94, a parainfluenza type 1 virus isolated from human multiple sclerosis brain.

ABSTRACT

A parainfluenza type 1 virus (6/94) recovered from brain cell cultures of two patients with multiple sclerosis (MS) was inoculated into newborn chimpanzees by the intranasal (IN) or intracerebral (IC) routes. Four of the five animals receiving the virus IN developed clinical signs ranging from mild fever, with or without rhinorrhea, to severe respiratory disease. Two of the chimpanzees died as a result of pneumonia. Virus could be recovered from respiratory tracts for as long as 9 days after exposure and was followed by development of specific neutralizing antibody to the 6/94 virus but not to the HA2 strain of parainfluenza type 1. Brain examination showed astrocytosis, especially of posterior fossa structures, activation of microgliacytes and, in one animal, round cell infiltration of leptomeninges. Of thse three animals receiving virus IC, two developed recurrent seizures beginning 14 months after inoculation. One of these was sacrificed at 23 months of age after progressive neurologic disease, with electroencephalographic abnormalities, developed. The third animal died at 3 months of age of intercurrent pneumonia. No virus was recovered from these animals, although all showed antibody conversion to 6/94 but not HA2 virus. A variety of pathologic lesions were seen in the brains of both animals coming to necropsy particularly in the sacrificed chimpanzee. These included subacute encephalitis, extensive cortical and subcortical degeneration, vascular sclerosis, white matter gliosis and axonal dystrophy.