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Universidad de Buenos Aires (20020110100128BA); Consejo Nacional de Investigaciones Cientificas y Tecnologicas (CONICET) (PIP-0443); Agencia de Promocion Cientifica y Tecnologica (ANPCyT, BID-PICT 761); DGICYT (Direccion General de Investigacion Cientifica y Tecnica) project BFU2012-31861; Fundacion Ramon Areces

In order to assess the effect of the antiviral Ribavirin on the course of Junín virus infection in Callithrix jacchus, seven inoculated monkeys were treated with 15 mg of the drug, twice a day, starting 6 days after infection when all animals were viremic. The three untreated controls showed typical signs of Junín virus infection at 14 days pi and their mean time of death was 18 days. In contrast, no signs of illness were detected in Ribavirin-treated animals until 24 days pi, when marmosets showed signs of neurological involvement: 5 of these animals died (mean day of death: 36) but the two remaining treated monkeys improved and survived infection without sequelae. The comparison of survival rates (0% vs 28%) and the delay of the mean day of death observed indicates that the Ribavirin treatment used has therapeutic effect on Junín virus infection in vivo.

2-day-old Wistar rats intracerebrally infected with the XJC13 strain of virus exhibited a 5% survival rate which rose to 71% after immune serum treatment. Brain viral titers were relatively unaffected by this treatment. Histologic studies showed necrosis in the cerebellum and brain cortex with mononuclear cell infiltration in both treated and nontreated groups. Beginning on day 16 postinfection, however, intracerebral perivascular gliosis foci and mild meningeal congestion were minimal in the treated animals. These findings imply that passively transferred humoral immunity leads to prompt recovery in this experimental model.

The effect of Junin virus infection on the active and passive delayed hyper-sensitivity of Jones Mote type in guinea pigs was studied. It was shown that in both types of hypersensitivity there is a suppression of the cutaneous reaction.

The effects of cyclophosphamide (CY), anti-mouse thymocyte sera, oxisuran, and cytosine arabinoside were evaluated in adult and newborn mice infected with Junin virus. Treatment with CY was the most effective, Adult mice, which are not normally susceptible to intracerebral infection with 10(3) LD50 of Junin virus, were rendered susceptible by treatment with an adequate dose and schedule of CY. However, CY-treated newborn mice were protected from death. This animal model may be suitable for use in pathogenesis and protection studies.

The effects of the administration of a bacterial endotoxin on the course of the Junin viral infection in the mouse were studied. The results showed that maximal protection against the disease was produced when both endotoxin and the virus were given on the day of birth. If endotoxin was administered first (on the day of birth) and was followed by the virus 24 hours later, a lesser degree of protection was obtained, but with a 48-hours interval there was no protection. If the virus was administered first (on the day of birth), followed by endotoxin 1 to 8 days later, the mortality was the same as with virus alone. If the interval between the administration of the virus and the endotoxin was 9 to 10 days, a very high mortality was observed in 24 hours, possibly due to an increased sensitivity of the infected mouse to the lethal effect of endotoxin. Viral titrations showed that the brains of endotoxin-protected mice contained enough virus to kill normal mice, indicating that the mere presence of the virus is not sufficient to produce death in the infected animals. Circulating antibodies to the virus were detectable 28 days after infection, i.e., about 13 days after the signs of the disease had disappeared. This fact and the failure of endotoxin-protected mice to survive a new challenge with Junin virus suggest that the protective phenomenon is not antibody-related. Since endotoxin fails to protect when given to mice either simultaneously with the virus 2 days after birth or one or more days after infection on the day of birth, it is very unlikely that an enhanced release of interferon might be responsible for the observed protection. Thymic function and its possible alteration by endotoxin is discussed.