Abstract
Replication of the diabetogenic variant of encephalomyocarditis virus (EMCV-D) in spleen cells and its association with subpopulations of spleen cells (L3T4+, Lyt-2+, Mac 1+, 33D1+ and AGM1 + cells) from both sexes of ICR Swiss mice were examined. Virus replication was limited to less than 0.5 log in suspensions of whole spleen cells, nonadherent cells or a B cell subfraction from both sexes of ICR Swiss mice following infection with EMCV-D at an MOI of 10; no virus replication was seen in adherent spleen cells from either sex. After 1 hour adsorption of EMCV-D onto spleen cells at a multiplicity of infection (MOI) of either 10 or 0.1, virus-associated cells were isolated using a monoclonal murine anti-EMCV-D and anti-mouse IgG conjugated to magnetic beads. Using an MOI of 0.1, less than 1 % of spleen cells bound virus particles after 1 hour adsorption at 4°C. Among the virus-positive cells, relatively higher percentages of adherent cell populations (Mac 1+ and 33D1 + cells) of both sexes bound virus particles within the first hour post-infection (PI) than did the other spleen cell subpopulations. Interferon (IFN)α/β production was detected as early as 4 hours PI in female spleen cell cultures infected with EMCV-D at an MOI of 0.1 while no IFNα/β activity was found in comparably infected male spleen cell cultures. Inhibiting IFNα/β activity in the virus-infected spleen cell cultures during the first 20 hours of infection using polyclonal rabbit anti-mouse IFNα/β serum eliminated production of IFNγ as well as IFNα/β. Spleen cell cultures depleted of adherent cells were unable to produce IFNα/β or IFNγ in the first 24 hours PI. The capacity to produce IFNγ at 12 hours after virus infection of spleen cells from both sexes of mice was restored to adherent cell-depleted cultures by addition of mouse IFNα/β at the time of infection. These results suggest that IFNα/β and adherent cells play critical roles in the early production of IFNγ (<16 hours PI) characteristic of the infected spleen cell cultures of females. Production of IFNα/β and IFNγ by spleen cells from both sexes of ICR Swiss mice was enhanced by administrating estrone to donor mice during the week before harvesting spleen cells. Virus-infected spleen cells from testosterone-treated females, but not males, exhibited shifts in the times of peak responses for each IFN activity to 4 hours earlier than those seen in virus-infected cells from untreated females. Spleen cells from testosterone-treated male mice showed suppressed activity in production of all 3 types of IFN.
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