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Reducing Viral Inhibition of Host Cellular Apoptosis Strengthens the Immunogenicity and Protective Efficacy of an Attenuated HSV-1 Strain.

Abstract
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.
AuthorsXingli Xu, Yufeng He, Shengtao Fan, Min Feng, Guorun Jiang, Lichun Wang, Ying Zhang, Yun Liao, Qihan Li
JournalVirologica Sinica (Virol Sin) Vol. 34 Issue 6 Pg. 673-687 (Dec 2019) ISSN: 1995-820X [Electronic] Netherlands
PMID31506828 (Publication Type: Journal Article)
Chemical References
  • Herpes Simplex Virus Vaccines
  • Vaccines, Attenuated
  • Viral Envelope Proteins
  • Viral Proteins
  • glycoprotein J, herpesvirus simiae
  • Protein Serine-Threonine Kinases
  • US3 protein, Human herpesvirus 1
Topics
  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Female
  • Herpes Simplex (pathology, prevention & control, virology)
  • Herpes Simplex Virus Vaccines (genetics, immunology)
  • Herpesvirus 1, Human (genetics, immunology)
  • Humans
  • Immunity
  • Jurkat Cells
  • Mice
  • Mice, Inbred BALB C
  • Mutation
  • Phenotype
  • Protein Serine-Threonine Kinases (genetics)
  • Vaccines, Attenuated (immunology)
  • Vero Cells
  • Viral Envelope Proteins (genetics)
  • Viral Proteins (genetics)
  • Virus Replication

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