Journal
NATURE IMMUNOLOGY
Volume 10, Issue 5, Pages 480-487Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.1720
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Funding
- Canadian Institutes for Health Research
- Natural Science and Engineering Research Council of Canada
- Fonds de la Recherche en Sante du Quebec
- US National Institutes of Health [EY09083]
- Research to Prevent Blindness
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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 1 beta 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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