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Nat Immunol. 2009 May;10(5):480-7. doi: 10.1038/ni.1720. Epub 2009 Mar 22.

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

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  • 1Département de Pathologie et Biologie Cellulaire, Université de Montréal, Succursale Centre-Ville, Montreal, Quebec, Canada.


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-gamma stimulated classical MHC class I presentation, fever-like hyperthermia and the pyrogenic cytokine interleukin 1beta 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.

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