Ectromelia virus replication in major target organs of innately resistant and susceptible mice after intravenous infection

Abstract

Summary. The kinetics of ectromelia virus replication in the spleen and liver and of a/13 interferon production in the spleen were determined during the first 3 days after intravenous infection with the virulent Moscow strain in resistant C57 BL/6 and susceptible DBA/2 mice. Virus replication in the spleen as measured by assays for virus DNA and infectious centers was suppressed in C57 BL/ 6 mice relative to DBA/2 mice within the first 1 or 2 days of infection. Infectious centers increased in DBA/2 mice but not in C57 BL/6 mice. Differences in virus replication between strains were less discrete when spleens were assayed for infectious virus than when they were assayed for infectious centers because infectious centers of most C57 BL/6 mice had more infectious virus than infectious centers of DBA/2 mice. Virus replication in the liver, the major target organ, as measured by virus DNA and infectious virus assays, was suppressed in C57 BL/6 mice relative to DBA/2 mice 3 days after infection but not before that interval. The results indicate that genetic control of ectromelia virus replication begins within the first 1 or 2 days of infection in the spleen but is delayed in the liver and that genetic control is directed at the prevention of virus spread more than at virus replication.

Ectromelia virus: the causative agent of mousepox

“…Many genetic factors that control disease appear to be involved in limiting virus spread during the first few days of infection, more so than limiting virus replication itself (Brownstein et al, 1993). By crossing DBA/2 and C57BL/6 mice, loci that confer a B6-like response to infection, and therefore contribute to host resistance to severe mousepox, could be identified.…”

Innate resistance to lethal mousepox is genetically linked to the NK gene complex on chromosome 6 and correlates with early restriction of virus replication by cells with an NK phenotype

“…Again, there was a highly significant difference between the spleen virus titers of control and asialo GM1 ϩ cell-depleted B6 mice ( Table 2, experiment 3B). These results showed that the asialo GM1 ϩ cell population of B6 mice, but not D2 mice, which included NK cells but may not have been specific for NK cells could suppress ectromelia virus titers during the first 72 h of infection, when genetic resistance is being expressed in the spleen (5). This difference in the effects of asialo GM1 ϩ cells on ectromelia virus titers between B6 and D2 mice was unlikely to have been a consequence of high levels of ectromelia virus in D2 mice overwhelming resistance mediated by NK cells because we showed in a previous study that on PID 2 and PID 3, only 2 and 15%, respectively, of spleen cells are infected with virus in intact D2 mice given the same dose of virus by the same route as in the study reported here (5).…”

Interaction between unrelated viruses during in vivo co-infection to limit pathology and immunity

“…We suggest in the former case LCMV-induced Type I IFN production is curtailed after 3 days to levels that are effectively blocked by ECTV proteins. In contrast, LCMV infection after establishment of ECTV infection is likely ineffective as ECTV proteins have effectively shut down Type I IFN signaling (55, 61). Our results also show that ECTV modulation of Type I IFN production during ECTV/LCMV co-infection attenuates LCMV-specific CD8 T cell responses that are dependent on direct signaling via Type I IFN for sustained proliferation.…”