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

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Abstract
MHC class I presentation of viral peptides aids CD8+ T cell recognition of infected cells. Desjardins and colleagues describe an MHC class I viral peptide presentation pathway that integrates autophagosomes and proteasome-dependent processes. 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.