Herpes simplex virus 1 interferes with autophagy of murine dendritic cells and impairs their ability to stimulate CD8+ T lymphocytes

Eur J Immunol. 2017 Oct;47(10):1819-1834. doi: 10.1002/eji.201646908. Epub 2017 Aug 31.

Abstract

The MHC class I presentation is responsible for the presentation of viral proteins to CD8+ T lymphocytes and mainly depends on the classical antigen processing pathway. Recently, a second pathway involving autophagy has been implicated in this process. Here, we show an increase in the capacity of murine dendritic cells (DCs) to present viral antigens on MHC class I after infection with a mutant herpes simplex virus 1 (HSV-1-Δ34.5), lacking infected cell protein 34.5 (ICP34.5), when compared to its parental HSV-1 strain. The ICP34.5 protein counteracts host cell translational arrest and suppresses macroautophagy, and the lack of this protein resulted in a low viral protein abundance, which was processed and presented in an efficient way. Our study demonstrates an important role of autophagy in processing endogenous viral proteins in HSV-1-infected DCs.

Keywords: Antigen presentation/processing; Autophagy; CD8+ T cells; Dendritic cells; Herpes simplex virus 1; MHC class 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigens, Viral / immunology
  • Autophagy / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / physiology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology
  • Dendritic Cells / virology
  • Herpesvirus 1, Human / genetics
  • Herpesvirus 1, Human / immunology*
  • Herpesvirus 1, Human / physiology*
  • Histocompatibility Antigens Class I / immunology
  • Lymphocyte Activation*
  • Mice
  • Viral Proteins / genetics
  • Viral Proteins / metabolism

Substances

  • Antigens, Viral
  • Histocompatibility Antigens Class I
  • Viral Proteins
  • gamma 34.5 protein, Human herpesvirus 1