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.
Herpes simplex virus-1 (HSV-1) is a major pathogen that causes various central nervous system (CNS) diseases,including herpes simplex encephalitis and meningitis.According to recent studies,PNKP significantly affects the proliferation of HSV-1 in astrocytes.Here,we used viral proliferation curves to confirm the significant inhibitory effects of PNKP on HSV-1 proliferation.PNKP downregulation was also confirmed by analyzing the transcription of viral genes.We found that PNKP downregulation affects the viral DNA copy number.This study preliminarily confirms that PNKP affects viral proliferation by affecting HSV-1 genome cyclization.These results also suggest that astrocytes play a specific role in preventing HSV-1 infection.
Lei YueSujie GuoXia CaoYing ZhangLe SunLongding LiuMin YanQihan Li
Studies of herpes simplex virus type 1 （HSV-1） infection have shown that many known and unknown cellular molecules in- volved in viral proliferation are up-regulated following HSV-1 infection. In this study, using two-dimensional polyacrylamide gel electrophoresis, we found that the expression of the HSV-1 infection response repressive protein （HIRRP, GI 16552881） was up-regulated in human L02 cells infected with HSV-1. HIRRP, an unknown protein, was initially localized in the cytoplasm and then translocated into the nucleus of HSV-l-infected cells. Further analysis showed that HIRRP represses HSV-1 proliferation by inhibiting transcription of the viral genome by interacting with the cellular transcription factor, ATFS, via its N-terminal domain. ATF5 represses the transcription of many host genes but can also act as an activator of genes containing a specific motif. We found that ATF5 promotes the proliferation of HSV-1 via a potential mechanism by which ATF5 enhances the transcription of viral genes during the course of an HSV-1 infection; HIRRP then induces feedback repression of this tran- scription by interacting with ATFS.
