INVITRO AND LONG-TERM INVIVO IMMUNE DYSFUNCTION AFTER INFECTION OF BALB C MICE WITH MOUSE HEPATITIS-VIRUS STRAIN A59/

Mouse hepatitis virus (MHV) is a pervasive pathogen in most mouse colo nies worldwide. Infection with this virus, which is often inadvertent and unrecognized, has previously been correlated in numerous anecdotal reports with immune modulation seriously affecting the outcome of bio medical experiments. Studies using experimental models to examine the effects of MHV infection have demonstrated that the virus can both sti mulate and depress immune function in vitro. We have used intranasal i nfection of MHV-susceptible BALB/c mice with MHV strain A59 to examine the effects of this virus on lymphoid tissue composition as well as i mmune function both in vitro and in vivo. We observed that the thymus, spleen, and lymph nodes underwent a transient period of marked cellul ar depletion. During that time, the percentages of T and B cells in th e spleen remained normal. However, within 1 week after inoculation, sp lenic lymphoid cell proliferation wag significantly decreased in respo nse to the T-cell stimuli, concanavalin A and anti-CD3 monoclonal anti body. This continued through day 35 but was resolved by 102 days posti noculation. Notably, at days 35 and 102, mice infected with MHV-A59 we re unable to reject skin grafts at a rate comparable to normal animals . These results support a basis for in vitro and, importantly, long-te rm in vivo immune dysfunction after infection with MHV.