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Immune mechanisms induced by an HSV-1 mutant strain: Discrepancy analysis of the immune system gene profile in comparison with a wild-type strain
Affiliation:1. Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan, China;2. Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China;3. University of Chinese Academy of Sciences, Beijing, China;1. Medical Faculty, Kunming University of Science and Technology, China;2. Kunming General Hospital of Chengdu Military Region, Kunming, China;3. Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands;4. Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China;1. Department of Swine Diseases, National Veterinary Research Institute, Partyzantów 57 Avenue, 24-100 Puławy, Poland;2. Department Poultry Viral Diseases, National Veterinary Research Institute, Partyzantów 57 Avenue, 24-100 Puławy, Poland;1. Department of Cadre''s Ward, the First People''s Hospital of Yunnan Province;2. Department of Respiratory Medicine, the First People''s Hospital of Yunnan Province;3. Department of Anesthesiology, Yan''an Hospital of Kunming City;4. Policy and Information Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
Abstract:Herpes simplex virus is a prevalent pathogen of humans of various age groups. The fact that no prophylactic or therapeutic vaccine is currently available suggests a significant need to further investigate the immune mechanisms induced by the virus and various vaccine candidates. We previously generated an HSV-1 mutant strain, M3, with partial deletions in ul7, ul41 and LAT that produced an attenuated phenotype in mice. In the present study, we performed a comparative analysis to characterize the immune responses induced by M3 versus wild-type HSV-1 in a mouse model. Infection with wild-type HSV-1 triggered an inflammatory-dominated response and adaptive immunity suppression and was accompanied by severe pathological damage. In contrast, infection with M3 induced a systematic immune response involving full activation of both innate and adaptive immunity and was accompanied by no obvious pathological changes. Furthermore, the immune response induced by M3 protected mice from lethal challenge with wild-type strains of HSV-1 and restrained virus proliferation and impaired latency. These data are useful for further HSV-1 vaccine development using a mutant strain construction strategy.
Keywords:HSV-1  Mutant strain  Gene expression  Vaccine
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