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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2020-07-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/12/7/770 |
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| author | Lei Liu Jishuai Cheng Tangwei Mou Ying Zhang Xingli Xu Jingjing Zhang Xueqi Li Xiao Feng Xiangxiong Xu Yun Liao Shengtao Fan Lichun Wang Guorun Jiang Qihan Li |
| author_facet | Lei Liu Jishuai Cheng Tangwei Mou Ying Zhang Xingli Xu Jingjing Zhang Xueqi Li Xiao Feng Xiangxiong Xu Yun Liao Shengtao Fan Lichun Wang Guorun Jiang Qihan Li |
| author_sort | Lei Liu |
| collection | DOAJ |
| 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 <i>RL1</i> (Repeat Long element 1) and/or <i>LAT</i> (Latency-associated Transcript) genes. The HSV-2 mutant strains <i>LAT-</i>HSV-2 and <i>RL1-LAT-</i>HSV-2 present different biological properties. The proliferation of <i>RL1-LAT-</i>HSV-2 in nerve cells was decreased significantly, and the plaques induced by <i>RL1-LAT-</i>HSV-2 in Vero cells were smaller than those induced by <i>LAT-</i>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 <i>RL1-LAT-</i>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 <i>LAT-</i>HSV-2 mutant containing the <i>LAT</i> gene deletion. However, the simultaneous mutation of both the <i>RL1</i> and <i>LAT</i> 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. |
| first_indexed | 2024-03-10T18:25:57Z |
| format | Article |
| id | doaj.art-94822c807d384597866d6b8f7e942098 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T18:25:57Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-94822c807d384597866d6b8f7e9420982023-11-20T07:02:09ZengMDPI AGViruses1999-49152020-07-0112777010.3390/v12070770The Mutation of the Genes Related to Neurovirulence in HSV-2 Produces an Attenuated Phenotype in MiceLei Liu0Jishuai Cheng1Tangwei Mou2Ying Zhang3Xingli Xu4Jingjing Zhang5Xueqi Li6Xiao Feng7Xiangxiong Xu8Yun Liao9Shengtao Fan10Lichun Wang11Guorun Jiang12Qihan Li13Institute of Medical Biology, Chinese Academy of Medicine Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming 650118, ChinaInstitute of Medical Biology, Chinese Academy of Medicine Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming 650118, ChinaInstitute of Medical Biology, Chinese Academy of Medicine Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming 650118, ChinaInstitute of Medical Biology, Chinese Academy of Medicine Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming 650118, ChinaInstitute of Medical Biology, Chinese Academy of Medicine Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming 650118, ChinaInstitute of Medical Biology, Chinese Academy of Medicine Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming 650118, ChinaInstitute of Medical Biology, Chinese Academy of Medicine Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming 650118, ChinaInstitute of Medical Biology, Chinese Academy of Medicine Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming 650118, ChinaInstitute of Medical Biology, Chinese Academy of Medicine Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming 650118, ChinaInstitute of Medical Biology, Chinese Academy of Medicine Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming 650118, ChinaInstitute of Medical Biology, Chinese Academy of Medicine Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming 650118, ChinaInstitute of Medical Biology, Chinese Academy of Medicine Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming 650118, ChinaInstitute of Medical Biology, Chinese Academy of Medicine Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming 650118, ChinaInstitute of Medical Biology, Chinese Academy of Medicine Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming 650118, ChinaHSV-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 <i>RL1</i> (Repeat Long element 1) and/or <i>LAT</i> (Latency-associated Transcript) genes. The HSV-2 mutant strains <i>LAT-</i>HSV-2 and <i>RL1-LAT-</i>HSV-2 present different biological properties. The proliferation of <i>RL1-LAT-</i>HSV-2 in nerve cells was decreased significantly, and the plaques induced by <i>RL1-LAT-</i>HSV-2 in Vero cells were smaller than those induced by <i>LAT-</i>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 <i>RL1-LAT-</i>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 <i>LAT-</i>HSV-2 mutant containing the <i>LAT</i> gene deletion. However, the simultaneous mutation of both the <i>RL1</i> and <i>LAT</i> 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.https://www.mdpi.com/1999-4915/12/7/770<i>RL1-LAT-</i>HSV-2<i>LAT-</i>HSV-2infectionimmune response |
| spellingShingle | Lei Liu Jishuai Cheng Tangwei Mou Ying Zhang Xingli Xu Jingjing Zhang Xueqi Li Xiao Feng Xiangxiong Xu Yun Liao Shengtao Fan Lichun Wang Guorun Jiang Qihan Li The Mutation of the Genes Related to Neurovirulence in HSV-2 Produces an Attenuated Phenotype in Mice Viruses <i>RL1-LAT-</i>HSV-2 <i>LAT-</i>HSV-2 infection immune response |
| 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 | <i>RL1-LAT-</i>HSV-2 <i>LAT-</i>HSV-2 infection immune response |
| url | https://www.mdpi.com/1999-4915/12/7/770 |
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