IMPAIRED RESPONSIVENESS TO GAMMA-INTERFERON OF MACROPHAGES INFECTED WITH LYMPHOCYTIC CHORIOMENINGITIS VIRUS CLONE-13 - SUSCEPTIBILITY TO HISTOPLASMOSIS

Lymphocytic choriomeningitis virus clone 13 (LCMV clone 13), a variant isolated from the spleens of neonatally infected mice, causes persist ent infections in mice infected as adults. Such persistently infected mice succumb to a normally sublethal dose of Histoplasma capsulatum, a nd their macrophages contain overwhelming numbers of yeast cells of th e fungus. Both LCMV clone 13 and H. capsulatum yeast cells target and replicate in macrophages of the host. We sought to study the effects o f LCMV clone 13 on the ability of macrophages to control growth of H. capsulatum in vitro. We show that the growth of H. capsulatum within m acrophages was not directly affected by the presence of LCMV clone 13, However, macrophages containing LCMV clone 13 did not respond fully t o gamma interferon (IFN-gamma) stimulation. Such unresponsiveness resu lted in proliferation of the fungus within macrophages cultured in the presence of IFN-gamma. The addition of anti-IFN-alpha/beta antibodies to LCMV clone 13-infected macrophage cultures restored macrophage res ponsiveness to IFN-gamma. These results indicate that production of IF N-alpha/beta by LCMV clone 13-infected macrophages antagonizes their r esponsiveness to IFN-gamma. Such antagonism may be one of the mechanis ms by means of which certain viruses cause immune suppression and susc eptibility to opportunistic infections.