Induction of Junin Virus Persistence in Adult Athymic Mice

Abstract

To determine the role of T lymphocytes in adult mice infected with Junin virus, 60-day-old athymic (nu/nu) mice and their immunocompetent (nu/+) littermates were inoculated intracerebrally with 10³ TCD50 of the XJ strain. None of them exhibited neurologic illness during a 6-month observation period, and mortality was 3% for nu/nu and 7% for nu/+ animals. The main features in infected nu/nu mice were: (i) high viral titers in brain, reaching a late peak (6.5 log/ml) 32 days postinoculation and persisting at least 6 months; (ii) low, late viremia appearing simultaneously with the viral peak in the central nervous system (CNS) and persisting up to 3 months after infection; (iii) absence of signs of neurologic disease or histologic lesions in brain and almost no mortality; and (iv) lack of detectable circulating antibodies either in IgM or in other immunoglobulins (Igs). Circulating anti-Junin antibodies were demonstrated in IgM and other Igs in immunocompetent mice, although no infectious virus or histologic lesions could be detected. These results show an important role for T lymphocytes in the clearence of Junin virus in the CNS, as demonstrated by viral persistence induced in adult athymic mice.

Reconstitution with T Lymphocytes Protects Nude Mice from a Central Nervous System Disorder Induced by a Temperature-sensitive Vesicular Stomatitis Virus

“…In contrast, tsG31-KS5 VSV inoculated into normal mice, either BALB/c (+/+) or Swiss outbred, produced an asymptomatic, persistent infection (Hughes et al, 1985 ;. Similar to temperature-sensitive VSV, adenovirus (Hashimoto & Umehara, 1977) and rabies virus (Kaplan et al, 1975) deleterious to normal mice than to nude mice (Zawatzky et al,1979); although Junin virus persisted and replicated in the CNS of nude mice, it did not cause any apparent clinical disease (Weissenbacher et al, 1986). Since some viruses do persist in the animals without inducing disease, the incomplete immune systems of the nude mice must be able to protect the animals from diseases produced by the viruses.…”

Epidemiology of argentine hemorrhagic fever

“…Finally, persistent JV infections have been described in cell culture (98), in wild reservoirs (79) and also in some experimental models, such as guinea pigs (55), rats (97) or congenitally athymic mice (92,96,71).…”

“…This strain readily induces persistent infections in genetically athymic mice (92,96) and in a low percentage of euthymic rats (97). However, the reproduction of the hemorrhagic picture resembling the h u m a n disease is only found in guinea pigs (88), m a r m o s e t s ,(91 ), or rhesus monkeys ( 58 ) while in suckling rodents, a lethal encephalitis is regularly observed.…”

“…Considerable evidence suggests that the T cell response is responsible for CNS damage in suckling mice since protection and absence of lesions were recorded in infected animals after thymectomy or t r e a t m e n t with i m m u n o s u p p r e s s o r s or in congenitally athymic mice (nu/'nu), These animals, whether adult or suckling, develop persistent a s y m p t o m a t i c infections with high brain virus titers and absence of lesions (92,96).…”

Mouse Splenocyte Transfer Effect Depends on Donor’s Junin Virus Infection Stage

“…The splenocytes from persistently infec ted mice seemed unable to modify the course of the persistent infection established in the athymic mouse, with no mortality, overt signs of disease or changes in viral levels, as is typical of this model [13]. This suggests an immune system alteration in mice persist ently infected with JV, where splenocytes cannot recognize JV antigen expressed in recipient-infected cells.…”