Pathogenicity of wild-type and temperature-sensitive mutants of herpes simplex virus type 2 in guinea pigs

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Abstract
The pathogenicity of herpes simplex virus type 2 strain 186, the wild-type (WT) strain, and four temperature-sensitive (ts) mutants was studied after genital inoculation of female guinea pigs. Infection with the WT virus was generally severe, with extensive skin lesions in 89% and mortality in 37% of inoculated animals. Guinea pigs inoculated with ts mutants manifest remarkably mild disease, with lesions occurring in only 16% of the guinea pits and a mortality rate of 7%. WT virus was recovered from nerve and non-nerve tissues of all acutely infected animals and from the majority of latently infected animals (71%). Virus was isolated from nerve or genital tissues from only 13% of ts mutant-inoculated animals during acute infection and from 7% during latent infection. Three of the seven isolates from mutant-infected animals appeared to be WT virus. Identification of WT and ts mutant isolates was done by biological characterization in selective cell cultures at permissive (33 degrees C) and nonpermissive (38 degrees C) temperatures. One month after initial infection with WT virus, guinea pigs were challenged with the same virus and were completely resistant to overt clinical disease. Animals inoculated with ts mutants A1b and C2b had mild manifestations of disease after challenge with WT virus; however, the capacity of WT virus to establish latent infection was conserved. Although complement-required neutralizing antibodies were detectable after challenge in animals previously inoculated with mutant virus A1b, C2b, or D6b, there was no significant protection against subsequent infection with WT virus. No complement-required neutralizing antibodies were detected in F3b animals after challenge. The present study of WT and ts mutants of herpes simplex virus type 2 in the guinea pig model provides a means for better understanding the mechanisms of pathogenesis and latency after genital infection.