Reducing Viral Inhibition of Host Cellular Apoptosis Strengthens the Immunogenicity and Protective Efficacy of an Attenuated HSV-1 Strain
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Herpes simplex virus 1 (HSV-1), a member of α herpesviruses, shows a high infectivity rate of 30%–60% in populations of various ages. Some herpes simplex (HSV) vaccine candidates evaluated during the past 20 years have not shown protective efficacy against viral infection. An improved understanding of the immune profile of infected individuals and the associated mechanism is needed. HSV uses an immune evasion strategy during viral replication, and various virus-encoded proteins, such as ICP47 and Vhs, participate in this process through limiting the ability of CD8+ cytotoxic T lymphocytes to recognize target cells. Other proteins, e.g., Us3 and Us5, also play a role in viral immune evasion via interfering with cellular apoptosis. In this work, to study the mechanism by which HSV-1 strain attenuation interferes with the viral immune evasion strategy, we constructed a mutant strain, M5, with deletions in the Us3 and Us5 genes. M5 was shown to induce higher neutralizing antibody titers and a stronger cellular immune response than our previously reported M3 strain, and to prevent virus infection more effectively than the M3 strain in an in vivo mouse challenge test.
KeywordsHerpes simplex virus 1 (HSV-1) Apoptosis M5 Us3 Us5
This work was supported by the National Natural Science Foundation of China (81802868 and 31670173); the Fundamental Research Funds for the Central Universities (3332018129, 3332018197); the CAMS Initiative for Innovative Medicine (2016-I2M-1-019); and the Science and Technology Major Project of Yunnan Province (2017ZF006 and 2017ZF020). The funders had no role in the study design, data collection and analysis, the decision to publish, or in the preparation of the manuscript.
QL and XX designed the experiments; XX, YH, SF, GJ, YL, and LW performed the experiments; XX, YZ, and YL performed the analyses; XX and MF wrote the manuscript. All of the authors read and approved the final version of the manuscript.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
Animal and Human Rights Statement
All institutional and national guidelines for the care and use of laboratory animals were followed. The experimental protocols were reviewed and approved by the Yunnan Provincial Experimental Animal Management Association (approval number: SCXK [Dian] 2013-0009).
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