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

Abstract

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.

Traditional Chinese Medicine as a Potential Source for HSV-1 Therapy by Acting on Virus or the Susceptibility of Host

“…Since no suitable drug is available for the treatment of latent HSV-1 infection in clinics yet, searching for strategies based on the prevention of transmission, suppression of reactivation, and viral shedding together with inhibition of epithelial damage is an effective measure to get out of the predicament of drug research and development against HSV-1. Moreover, some mutated HSV-1 strains produced by the CRISPR/Cas9 system could be potential vaccines in full swing for the prevention of HSV-1 in humans [ 91 , 92 ].…”

Attenuated Phenotype and Immunogenic Characteristics of a Mutated Herpes Simplex Virus 1 Strain in the Rhesus Macaque

“…The M3 mutated strain was constructed via partial deletion of the UL7 , UL41 , and LAT genes according to the methods described in our previous work [ 23 ]. In this study, the M3 virus that proliferated in Vero cells was identified again by specific PCR detection of the deleted sequences of UL7 , UL41 , and LAT genes, and the viral titer was determined in a microtitration assay [ 23 ].…”

“…This mutant HSV-1 showed a reduced viral proliferative rate in cultured cells and decreased virulence in mice by modulating the viral transcription of the genes [ 22 ]. The mutant M3 strain, which was based on M1, was obtained via mutations in the UL7 , UL41 , and LAT genes and exhibited an attenuated phenotype in mice [ 23 ]. However, with the biological difference and as a non-natural host for HSV-1, the mouse is not thought to be capable of providing data for the real process of the viral interactions with human tissues, especially for pathological events occurring during the latent phase [ 24 ].…”

Characteristics of herpes simplex virus infection and pathogenesis suggest a strategy for vaccine development

“…The deletion of the ul7 gene eliminates this colocalization but does not affect viral structural . Interestingly, partial deletion of this gene could limit viral proliferation and lead to delayed growth kinetics of the virus in cultured cells or animals because UL7 regulates the transcription of the viral α‐gene, and this partial deletion could provide an attenuated viral phenotype (Figure ) . Other studies have also suggested that VP22, which is encoded by the ul49 gene, is capable of interacting with cellular cGAS and inhibiting its enzymatic activity, as VP22 functions in the viral structural network .…”