Susceptible adult murine model for Junin virus

Abstract

The adult mouse model had been considered resistant to Junin virus (JV) infection. However, we found that C3H/HeJ murine strain proved highly susceptible up to 5 months of age to intracerebral inoculation with the prototype XJ JV strain, showing neurological signs and 80-90% mortality within 13 days. Neutralizing antibodies (Nt Ab) were absent, but low immunofluorescent Ab levels (1:5) were detected as from day +7. The virus could only be rescued by coculture of brain samples with Vero cells. Histopathological findings were consistent with the suckling mouse model and with a delayed-type hypersensitivity reaction. XJ inoculation by extraneural routes failed to cause disease, however, it induced Nt Abs. Ic infection with XJCL3 strain of JV attenuated for man and guinea pig, but not for mouse, induced high Nt Ab levels but not mortality. In either case, mice resisted ic XJ challenge. Thus, C3H/HeJ is the first adult mouse model susceptible to JV.

Arenavirus Glycan Shield Promotes Neutralizing Antibody Evasion and Protracted Infection

“…The failure to detect a putative Glc11 effect in suckling mice [ 39 ] could have been due to these young animals’ immunological immaturity, which entails reduced antibody responsiveness [ 71 ]. In addition, the more rapid disease course in mice (~10 days) as compared to guinea pigs (~18 days) may have outpaced nAb effects [ 53 , 70 , 72 ]. Alternatively, cell-mediated immunity may control primary Candid#1 infection largely independently of nAb responses [ 53 ].…”

Junín Virus Pathogenesis and Virus Replication

“…Adult C3H/HeJ mice, a mouse strain lacking toll like receptor (TLR)-4, are susceptible to Junín XJ strain when infected i.c., causing a high mortality rate within 13 days with no neutralizing antibodies and apparent delayed-type hypersensitivity reaction. This strain is not susceptible to other routes of infection outside the central nervous system (CNS) [30]. TLR-4 is responsible for pathogen recognition and activation of the innate immune system.…”

Effect of Ribavirin on Junin Virus Infection in Guinea Pigs

“…Several experimental animals have been utilized to study JUNV pathogenesis including various rodent species (C3H and athymic mice, guinea pigs, and rats) and non‐human primates ( Cebus apella , Callithrix jacchus and Macaca mulatta ) (Barrios et al., 1982; McKee et al., 1985; Avila et al., 1987; Carballal et al., 1987; Campetella et al., 1988; Kenyon et al., 1988). These models vary in their pathogenetic patterns, lethal infectious dose (LD 50 ), virus distribution and overall survival time depending upon virus strain, passage history and age of the animals.…”