The role of circulating interferon in the modifications of immune responsiveness by mouse hepatitis virus (MHV-3).

MHV-3 modifies the humoral immune response to SRBC. During acute infections timing was critical: infecting mice before antigen administration led to immunodepression. Simultaneous injection with virus and SRBC resulted in immunostimulation. Persistent MHV-3 infections were associated with a chronic immunodepression. The presence of circulating interferon (IF) was well correlated with these modifications. IF peaking before antigen was associated with immunodepression whereas IF secretion after antigen was associated with immunostimulation. Low, permanent levels of IF were associated with chronic immunodepression. Since IF is, up to now, the only product of activated lymphocytes that has been shown to modulate immune responses, our results suggest that induction of IF by MHV-3 may be the main mechanism by which this virus modifies immune responsiveness. Moreover, we have shown that MHV-3 infection in susceptible mice diminishes the secretion of lymphocyte IF in response to Sendai virus. In these animals, the thymus cortex was profoundly depleted although the thymus medulla remained unchanged. The MHV-3 infection may, therefore, interfere with a subpopulation of IF-secreting lymphocytes. The possible physiologic role of such lymphocyte subpopulation in terms of host-virus relationships is discussed.