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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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.
Keywordsherpes simplex virus 1 (HSV-1) UL7 UL41 LAT mutant
This work was supported by the National Basic Research Program (2012CB518901), Chinese academy of medical sciences (CAMS) Initiative for Innovative Medicine (2016-I2M-1-019), the National Natural Science Foundation of China (31300143, 31100127), and the Fundamental Research Funds for the Central Universities (2016ZX310047, 2016ZX350072). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
QHL designed the experiments; XLX, STF, PFC, LCW and XLZ performed the experiments; XLX, YZ and YL performed the analyses; XLX and MF wrote the manuscript; YQG completed the majority of the manuscript revisions and refined the English used in the manuscript, and all of the authors contributed to, read, and approved the final version of the manuscript.
Compliance with Ethics Guidelines
The authors declare that they have no conflict of interest. The experimental protocols were reviewed and approved by the Yunnan Provincial Experimental Animal Management Association (approval number: SCXK [Dian] 2011–0005) and the Experimental Animal Ethics Committee of the Institute of Medical Biology, Chinese Academy of Medical Sciences. The animal experiments were designed based on the principles expressed in the “Guide for the Care and Use of Laboratory Animals” and “Guidance for Experimental Animal Welfare and Ethical Treatment.” All institutional and national guidelines for the care and use of laboratory animals were followed.
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