Autophagy enhances the presentation of endogenous viral antigens on MHC class I molecules during HSV-1 infection

Luc English, Magali Chemali, Johanne Duron, Christiane Rondeau, Annie Laplante, Diane Gingras, Diane Alexander, David Leib, Christopher Norbury, Roger Lippé, Michel Desjardins

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303 Scopus citations

Abstract

Viral proteins are usually processed by the 'classical' major histocompatibility complex (MHC) class I presentation pathway. Here we showed that although macrophages infected with herpes simplex virus type 1 (HSV-1) initially stimulated CD8+ T cells by this pathway, a second pathway involving a vacuolar compartment was triggered later during infection. Morphological and functional analyses indicated that distinct forms of autophagy facilitated the presentation of HSV-1 antigens on MHC class I molecules. One form of autophagy involved a previously unknown type of autophagosome that originated from the nuclear envelope. Whereas interferon-γ stimulated classical MHC class I presentation, fever-like hyperthermia and the pyrogenic cytokine interleukin 1β activated autophagy and the vacuolar processing of viral peptides. Viral peptides in autophagosomes were further processed by the proteasome, which suggests a complex interaction between the vacuolar and MHC class I presentation pathways.

Original languageEnglish (US)
Pages (from-to)480-487
Number of pages8
JournalNature Immunology
Volume10
Issue number5
DOIs
StatePublished - 2009

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    English, L., Chemali, M., Duron, J., Rondeau, C., Laplante, A., Gingras, D., Alexander, D., Leib, D., Norbury, C., Lippé, R., & Desjardins, M. (2009). Autophagy enhances the presentation of endogenous viral antigens on MHC class I molecules during HSV-1 infection. Nature Immunology, 10(5), 480-487. https://doi.org/10.1038/ni.1720