title: Immunosuppression promotes ocular virus replication and CNS neurovirulence following corneal inoculation with an avirulent herpes simplex type 1 thymidine kinase negative mutant.
abstract: The present study determined the effect of immunosuppression on the pathogenicity of an avirulent HSV-1 thymidine kinase negative mutant in the murine model. Following corneal inoculation with an HSV-1 TK- mutant, normal and cyclophosphamide-immunosuppressed outbred mice were evaluated for keratitis, ocular, trigeminal ganglia, and forebrain virus titers, survival, and latency. Immunosuppression enhanced virus pathogenicity producing greater keratitis, higher ocular, trigeminal, and forebrain virus titers, decreased survival, and increased trigeminal ganglionic residual infectious virus and latency. Our results suggest that both normal host defenses as well as the virus thymidine kinase expression contribute to HSV-1 pathogenicity.
mesh_terms: D000818:Animals; D001927:Brain Diseases / Q000382:microbiology*; D003520:Cyclophosphamide / Q000494:pharmacology; D006561:Herpes Simplex / Q000382:microbiology*; D007165:Immunosuppression Therapy / Q000009:adverse effects*; D007635:Keratitis, Dendritic / Q000382:microbiology*; D008297:Male; D051379:Mice; D009154:Mutation; D018139:Simplexvirus / Q000201:enzymology / Q000302:isolation & purification / Q000472:pathogenicity*; D013937:Thymidine Kinase / Q000172:deficiency; D014276:Trigeminal Nerve / Q000382:microbiology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D003520:Cyclophosphamide; D013937:Thymidine Kinase