Attenuated phenotypes and analysis of a herpes simplex virus 1strain with partial deletion of the UL7, UL41 and LAT genes

We previously constructed a herpes simplex virus 1(HSV-1) UL7 mutant virus(M1) and showed that a partial deletion mutation of the UL7 gene led to a lower proliferative rate and an attenuated phenotype. Using the M1 mutant, we further modified the UL41 gene, which encodes another tegument protein, and the latency-associated transcript(LAT) gene. Observations of the resulting mutants with modified UL7 and UL41(M2) or UL7, UL41 and LAT(M3) genes indicated attenuated phenotypes, with lower proliferative ratios in various cells, non-lethal infections in mice and lower viral loads in nervous tissues compared with the wild-type strain. Furthermore, no LAT stable intron could be detected in the trigeminal ganglion of M3-infected animals. The results obtained with the three HSV-1 mutants indicate that the M3 mutant is an attenuated strain with low pathogenicity during both acute and latent infections. Together, the results support the use of the M3 mutant as a candidate for the development of an HSV-1 vaccine.