The responses of nude-athymic mice to nominally avirulent togavirus infections

Abstract

Following intraperitoneal infection by an avirulent strain of Semliki Forest virus, athymic nude mice showed almost normal clearance of viraemia and a transitory peak of antibody activity at 5 to 9 days which fell to less than about 0.1% of the normal antibody activity from the 14th day. When nude mice received a transfer of normal spleen cells from sex-matched litter mates at 1 day before infection, a pattern of high and continous antibody synthesis was established for at least the following 7 weeks. This clear T-cell dependence of the regulation of serum antibody synthesis was unrelated to the development of regulatory (pre-challenge) or protective (post-challenge) immunity since, particularly for female nude mice, up to 60% were benignly and protectively infected in the absence of detectable antibody activity. The brains of such nude mice showed persistence of infectivity for at least 7 weeks at 10 to 10(4) p.f.u./brain after avirulent infection and at about 10(3) to 10(4) p.f.u./brain after virulent challenge. The prior transfer of normal spleen cells to nude mice enabled them to clear brain infectivity as efficiently as normal mice. These results are discussed in terms of the evident interplay of both T-lymphocyte dependent and T-lymphocyte independent functions in the control of brain infectivity, in the expression of virulence and in the stimulation of regulatory and protective immunity.