Effect of macrophage activation on resistance of mouse peritoneal macrophages to infection with herpes simplex virus types 1 and 2.

Summary To define the effect of heterogeneity of murine peritoneal macrophages (Mo) on intrinsic resistance to herpes simplex virus (HSV) infection, several Mo populations were characterized for their response to infection with HSV type 1 (HSV-1) and HSV-2. Steady-state resident Mo (Res Mo) were compared in parallel with Mo activated with Corynebacterium parvum (now designated Propionibacterium acnes) (CP Mo) and thioglycollate-elicited inflammatory Mo (TG Mo). Res Mo were completely non-permissive for productive virus infection and showed no c.p.e. The intrinsic resistance of CP Mo to HSV infection was similar to that of Res Mo, in that the infection was non-productive for infectious virus, but CP Mo showed marked c.p.e. TG Mo showed semi-permissiveness, with virus yields at least 10-fold higher than those in Res Mo and CP Mo, and marked c.p.e. The three distinct intrinsic response patterns were maintained regardless of whether Mo were derived from CD-1 or B6C3F1 mice, or whether the infecting virus was HSV-1 or HSV-2. To define the level at which Mo restrict HSV replication, immunofluorescence assays for viral antigens and hybridization analyses for viral DNA were performed. All Mo populations showed immediate early and early virus polypeptides. Res Mo and CP Mo showed no viral DNA replication, but TG Mo showed moderate levels of viral DNA synthesis that paralleled the infectious virus titres produced. Investigation of the mechanism for the heterogeneous intrinsic antiviral response among the Mo revealed that interferon was not involved, because antiserum to mouse α/β interferon did not alter the intrinsic resistance patterns. Induction of c.p.e. in Mo required live, replication-competent HSV. The involvement of tumour necrosis factor (TNF) in c.p.e. was found to be unlikely; no significant amounts of TNF were detected in the culture medium of the Mo, and inclusion of anti-TNF antibody did not inhibit c.p.e.