The responses of nude-athymic mice to nominally avirulent togavirus infections -- Bradish et al. 42 (3): 555 -- Journal of General Virology

This study examined how athymic nude mice (lacking T-lymphocytes) respond to infection with avirulent Semliki Forest virus compared to normal littermates. Nude mice showed transient antibody production peaking at day 5-9, then declining to negligible levels by day 14, whereas normal mice sustained antibody synthesis. When nude mice received normal spleen cell transfers one day before infection, antibody synthesis was restored to normal levels. Notably, some nude mice (up to 60% of females) survived avirulent infection and were protected against subsequent virulent challenge despite lacking detectable antibodies. However, nude mice showed persistent brain virus (10^3-10^4 p.f.u./brain for 7 weeks) that was cleared only after spleen cell transfer. The study demonstrated that T-cell-dependent and T-cell-independent mechanisms regulate different aspects of the immune response: early IgM synthesis and viraemia clearance were largely T-cell independent, while sustained antibody synthesis and brain virus clearance were T-cell dependent. The results reveal complex interactions between cellular and humoral immunity in controlling viral infection and protecting against virulent challenge.

Key findings

• Nude mice showed transient antibody synthesis (peaking day 5-9) that was T-cell dependent and could be restored to normal levels by spleen cell transfer
• Up to 60% of athymic mice survived avirulent infection and were protected against lethal virulent challenge despite lacking detectable serum antibodies, indicating T-cell-independent protective mechanisms
• Early viraemia clearance and IgM synthesis were largely T-cell independent, but sustained antibody synthesis and clearance of brain infectivity required T-cell functions
• Nude mice developed persistent brain viral infection (10^3-10^4 p.f.u./brain) lasting at least 7 weeks, which correlated inversely with serum antibody activity and was eliminated by spleen cell transfer
• The expression of virulence and control of brain infection involved interplay of both T-cell-dependent and T-cell-independent mechanisms, suggesting roles for macrophages and antibodies in viral regulation