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

Abstract

To define the effect of heterogeneity of murine peritoneal macrophages (M phi) on intrinsic resistance to herpes simplex virus (HSV) infection, several M phi populations were characterized for their response to infection with HSV type 1 (HSV-1) and HSV-2. Steady-state resident M phi (Res M phi) were compared in parallel with M phi activated with Corynebacterium parvum (now designated Propionibacterium acnes) (CP M phi) and thioglycollate-elicited inflammatory M phi (TG M phi). Res M phi were completely non-permissive for productive virus infection and showed no c.p.e. The intrinsic resistance of CP M phi to HSV infection was similar to that of Res M phi, in that the infection was non-productive for infectious virus, but CP M phi showed marked c.p.e. TG M phi showed semi-permissiveness, with virus yields at least 10-fold higher than those in Res M phi and CP M phi, and marked c.p.e. The three distinct intrinsic response patterns were maintained regardless of whether M phi 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 M phi restrict HSV replication, immunofluorescence assays for viral antigens and hybridization analyses for viral DNA were performed. All M phi populations showed immediate early and early virus polypeptides. Res M phi and CP M phi showed no viral DNA replication, but TG M phi 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 M phi revealed that interferon was not involved, because antiserum to mouse alpha/beta interferon did not alter the intrinsic resistance patterns. Induction of c.p.e. in M phi 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 M phi, and inclusion of anti-TNF antibody did not inhibit c.p.e.