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The Mutation of the Genes Related to Neurovirulence in HSV-2 Produces an Attenuated Phenotype in Mice

HSV-2 (Herpes simplex virus type 2) is a critical viral agent that mainly causes genital herpes and life-long latent infection in the dorsal root ganglia. Gene modification via CRISPR/Cas9 Clustered regularly interspaced short palindromic repeat sequences/CRISPR associated 9) was used here to constr...

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Autores principales: Liu, Lei, Cheng, Jishuai, Mou, Tangwei, Zhang, Ying, Xu, Xingli, Zhang, Jingjing, Li, Xueqi, Feng, Xiao, Xu, Xiangxiong, Liao, Yun, Fan, Shengtao, Wang, Lichun, Jiang, Guorun, Li, Qihan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412103/
https://www.ncbi.nlm.nih.gov/pubmed/32708847
http://dx.doi.org/10.3390/v12070770
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author Liu, Lei
Cheng, Jishuai
Mou, Tangwei
Zhang, Ying
Xu, Xingli
Zhang, Jingjing
Li, Xueqi
Feng, Xiao
Xu, Xiangxiong
Liao, Yun
Fan, Shengtao
Wang, Lichun
Jiang, Guorun
Li, Qihan
author_facet Liu, Lei
Cheng, Jishuai
Mou, Tangwei
Zhang, Ying
Xu, Xingli
Zhang, Jingjing
Li, Xueqi
Feng, Xiao
Xu, Xiangxiong
Liao, Yun
Fan, Shengtao
Wang, Lichun
Jiang, Guorun
Li, Qihan
author_sort Liu, Lei
collection PubMed
description HSV-2 (Herpes simplex virus type 2) is a critical viral agent that mainly causes genital herpes and life-long latent infection in the dorsal root ganglia. Gene modification via CRISPR/Cas9 Clustered regularly interspaced short palindromic repeat sequences/CRISPR associated 9) was used here to construct HSV-2 mutant strains through the deletion of fragments of the RL1 (Repeat Long element 1) and/or LAT (Latency-associated Transcript) genes. The HSV-2 mutant strains LAT-HSV-2 and RL1-LAT-HSV-2 present different biological properties. The proliferation of RL1-LAT-HSV-2 in nerve cells was decreased significantly, and the plaques induced by RL1-LAT-HSV-2 in Vero cells were smaller than those induced by LAT-HSV-2 mutant and wild-type strains. The observation of mice infected with these two mutants compared to mice infected with the wild-type strain indicated that the mutant RL1-LAT-HSV-2 has an attenuated phenotype with reduced pathogenicity during both acute and latent infections and induces a stronger specific immune response than the wild-type strain, whereas the attenuation effect was not found in mice infected with the LAT-HSV-2 mutant containing the LAT gene deletion. However, the simultaneous mutation of both the RL1 and LAT genes did not completely restrict viral proliferation in nerve cells, indicating that multiple HSV genes are involved in viral replication in the neural system. This work suggests that the HSV-2 genes RL1 and/or LAT might be involved in the virulence mechanisms in mouse infections.
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spelling pubmed-74121032020-08-25 The Mutation of the Genes Related to Neurovirulence in HSV-2 Produces an Attenuated Phenotype in Mice Liu, Lei Cheng, Jishuai Mou, Tangwei Zhang, Ying Xu, Xingli Zhang, Jingjing Li, Xueqi Feng, Xiao Xu, Xiangxiong Liao, Yun Fan, Shengtao Wang, Lichun Jiang, Guorun Li, Qihan Viruses Article HSV-2 (Herpes simplex virus type 2) is a critical viral agent that mainly causes genital herpes and life-long latent infection in the dorsal root ganglia. Gene modification via CRISPR/Cas9 Clustered regularly interspaced short palindromic repeat sequences/CRISPR associated 9) was used here to construct HSV-2 mutant strains through the deletion of fragments of the RL1 (Repeat Long element 1) and/or LAT (Latency-associated Transcript) genes. The HSV-2 mutant strains LAT-HSV-2 and RL1-LAT-HSV-2 present different biological properties. The proliferation of RL1-LAT-HSV-2 in nerve cells was decreased significantly, and the plaques induced by RL1-LAT-HSV-2 in Vero cells were smaller than those induced by LAT-HSV-2 mutant and wild-type strains. The observation of mice infected with these two mutants compared to mice infected with the wild-type strain indicated that the mutant RL1-LAT-HSV-2 has an attenuated phenotype with reduced pathogenicity during both acute and latent infections and induces a stronger specific immune response than the wild-type strain, whereas the attenuation effect was not found in mice infected with the LAT-HSV-2 mutant containing the LAT gene deletion. However, the simultaneous mutation of both the RL1 and LAT genes did not completely restrict viral proliferation in nerve cells, indicating that multiple HSV genes are involved in viral replication in the neural system. This work suggests that the HSV-2 genes RL1 and/or LAT might be involved in the virulence mechanisms in mouse infections. MDPI 2020-07-17 /pmc/articles/PMC7412103/ /pubmed/32708847 http://dx.doi.org/10.3390/v12070770 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Lei
Cheng, Jishuai
Mou, Tangwei
Zhang, Ying
Xu, Xingli
Zhang, Jingjing
Li, Xueqi
Feng, Xiao
Xu, Xiangxiong
Liao, Yun
Fan, Shengtao
Wang, Lichun
Jiang, Guorun
Li, Qihan
The Mutation of the Genes Related to Neurovirulence in HSV-2 Produces an Attenuated Phenotype in Mice
title The Mutation of the Genes Related to Neurovirulence in HSV-2 Produces an Attenuated Phenotype in Mice
title_full The Mutation of the Genes Related to Neurovirulence in HSV-2 Produces an Attenuated Phenotype in Mice
title_fullStr The Mutation of the Genes Related to Neurovirulence in HSV-2 Produces an Attenuated Phenotype in Mice
title_full_unstemmed The Mutation of the Genes Related to Neurovirulence in HSV-2 Produces an Attenuated Phenotype in Mice
title_short The Mutation of the Genes Related to Neurovirulence in HSV-2 Produces an Attenuated Phenotype in Mice
title_sort mutation of the genes related to neurovirulence in hsv-2 produces an attenuated phenotype in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412103/
https://www.ncbi.nlm.nih.gov/pubmed/32708847
http://dx.doi.org/10.3390/v12070770
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