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