In vivo and in vitro models of demyelinating disease. IX. Progression of JHM virus infection in the central nervous system of the rat during overt and asymptomatic phases.
JHM virus, when inoculated into neonatal rats, can cause either a rapidly fatal acute encephalomyelitis or, after longer incubation periods, a paralytic disease. The cerebrospinal fluid (CSF) and serum anti-JHM virus IgG concentrations present in rats prior to onset of clinical symptoms or during the acute and paralytic phases of disease were compared. High CSF/serum ratios, indicative of local antibody production in the CNS, were noted only where disease was demonstrable suggesting that local antibody production accompanied the infection but did not prevent the neurological disease. Among animals in which neurologic symptoms had not become manifest, only those with elevated CSF/serum ratios were found to have histological CNS lesions. Immunofluorescent microscopy indicated that viral antigens were present in both glia and neurons. Antigen-positive cells were frequently present in histologically normal CNS tissue, while regions of necrosis were antigen negative. Testing for the presence of viral RNA with JHM cDNA probes revealed that the virus was rapidly disseminated throughout the CNS, presumably establishing centers of infection prior to the development of recognizable tissue damage. Viral RNA was also detected in the CNS following recovery from paralysis and as late as 5 months postinfection, where no disease occurred. These findings indicate that, although infection by JHM virus can spread rapidly throughout the CNS, formation of lesions during chronic disease is a slower process. The current data and previous observations suggest that JHM virus can remain in a latent state for periods of at least several months in rats without apparent neurologic disease despite the absence of any known provirus phase in the replicative strategy of coronaviruses.
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D000917:Antibody Formation; D000956:Antigens, Viral / Q000032:analysis; D001921:Brain / Q000382:microbiology / Q000473:pathology; D003332:Coronaviridae / Q000472:pathogenicity*; D003333:Coronaviridae Infections / Q000382:microbiology* / Q000473:pathology; D004247:DNA / Q000302:isolation & purification; D004279:DNA, Viral / Q000235:genetics; D003711:Demyelinating Diseases / Q000382:microbiology* / Q000473:pathology; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D051381:Rats; D011919:Rats, Inbred Strains; D011920:Rats, Inbred WF
D000914:Antibodies, Viral; D000956:Antigens, Viral; D004279:DNA, Viral; D004247:DNA