Attenuated Phenotype and Immunogenic Characteristics of a Mutated Herpes Simplex Virus 1 Strain in the Rhesus Macaque
Herpes simplex virus type 1(HSV-1) presents a conundrum to public health worldwide because of its specific pathogenicity and clinical features. Some experimental vaccines, such as the recombinant viral glycoproteins, exhibit the viral immunogenicity of a host-specific immune response, but none of th...
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MDPI AG
2018-05-01
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| Series: | Viruses |
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| Online Access: | http://www.mdpi.com/1999-4915/10/5/234 |
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| author | Shengtao Fan Xingli Xu Yun Liao Yongrong Wang Jianbin Wang Min Feng Lichun Wang Ying Zhang Zhanlong He Fengmei Yang Nigel W. Fraser Qihan Li |
| author_facet | Shengtao Fan Xingli Xu Yun Liao Yongrong Wang Jianbin Wang Min Feng Lichun Wang Ying Zhang Zhanlong He Fengmei Yang Nigel W. Fraser Qihan Li |
| author_sort | Shengtao Fan |
| collection | DOAJ |
| description | Herpes simplex virus type 1(HSV-1) presents a conundrum to public health worldwide because of its specific pathogenicity and clinical features. Some experimental vaccines, such as the recombinant viral glycoproteins, exhibit the viral immunogenicity of a host-specific immune response, but none of these has achieved a valid epidemiological protective efficacy in the human population. In the present study, we constructed an attenuated HSV-1 strain M3 through the partial deletion of UL7, UL41, and the latency-associated transcript (LAT) using the CRISPR/Cas9 system. The mutant strain exhibited lowered infectivity and virulence in macaques. Neutralization testing and ELISpot detection of the specific T-cell responses confirmed the specific immunity induced by M3 immunization and this immunity defended against the challenges of the wild-type strain and restricted the entry of the wild-type strain into the trigeminal ganglion. These results in rhesus macaques demonstrated the potential of the attenuated vaccine for the prevention of HSV-1 in humans. |
| first_indexed | 2024-12-14T14:53:39Z |
| format | Article |
| id | doaj.art-ded69b218fb44d019ee193ee7de90ca9 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-14T14:53:39Z |
| publishDate | 2018-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-ded69b218fb44d019ee193ee7de90ca92022-12-21T22:57:03ZengMDPI AGViruses1999-49152018-05-0110523410.3390/v10050234v10050234Attenuated Phenotype and Immunogenic Characteristics of a Mutated Herpes Simplex Virus 1 Strain in the Rhesus MacaqueShengtao Fan0Xingli Xu1Yun Liao2Yongrong Wang3Jianbin Wang4Min Feng5Lichun Wang6Ying Zhang7Zhanlong He8Fengmei Yang9Nigel W. Fraser10Qihan Li11Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, ChinaYunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, ChinaYunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, ChinaYunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, ChinaYunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, ChinaYunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, ChinaYunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, ChinaYunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, ChinaInstitute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, ChinaInstitute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, ChinaDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USAYunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, ChinaHerpes simplex virus type 1(HSV-1) presents a conundrum to public health worldwide because of its specific pathogenicity and clinical features. Some experimental vaccines, such as the recombinant viral glycoproteins, exhibit the viral immunogenicity of a host-specific immune response, but none of these has achieved a valid epidemiological protective efficacy in the human population. In the present study, we constructed an attenuated HSV-1 strain M3 through the partial deletion of UL7, UL41, and the latency-associated transcript (LAT) using the CRISPR/Cas9 system. The mutant strain exhibited lowered infectivity and virulence in macaques. Neutralization testing and ELISpot detection of the specific T-cell responses confirmed the specific immunity induced by M3 immunization and this immunity defended against the challenges of the wild-type strain and restricted the entry of the wild-type strain into the trigeminal ganglion. These results in rhesus macaques demonstrated the potential of the attenuated vaccine for the prevention of HSV-1 in humans.http://www.mdpi.com/1999-4915/10/5/234HSV-1mutant strainimmunogenicityrhesus macaques |
| spellingShingle | Shengtao Fan Xingli Xu Yun Liao Yongrong Wang Jianbin Wang Min Feng Lichun Wang Ying Zhang Zhanlong He Fengmei Yang Nigel W. Fraser Qihan Li Attenuated Phenotype and Immunogenic Characteristics of a Mutated Herpes Simplex Virus 1 Strain in the Rhesus Macaque Viruses HSV-1 mutant strain immunogenicity rhesus macaques |
| title | Attenuated Phenotype and Immunogenic Characteristics of a Mutated Herpes Simplex Virus 1 Strain in the Rhesus Macaque |
| title_full | Attenuated Phenotype and Immunogenic Characteristics of a Mutated Herpes Simplex Virus 1 Strain in the Rhesus Macaque |
| title_fullStr | Attenuated Phenotype and Immunogenic Characteristics of a Mutated Herpes Simplex Virus 1 Strain in the Rhesus Macaque |
| title_full_unstemmed | Attenuated Phenotype and Immunogenic Characteristics of a Mutated Herpes Simplex Virus 1 Strain in the Rhesus Macaque |
| title_short | Attenuated Phenotype and Immunogenic Characteristics of a Mutated Herpes Simplex Virus 1 Strain in the Rhesus Macaque |
| title_sort | attenuated phenotype and immunogenic characteristics of a mutated herpes simplex virus 1 strain in the rhesus macaque |
| topic | HSV-1 mutant strain immunogenicity rhesus macaques |
| url | http://www.mdpi.com/1999-4915/10/5/234 |
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