Abstract
Autophagy delivers cytoplasmic constituents for lysosomal degradation, and thereby facilitates pathogen degradation and pathogen fragment loading onto MHC molecules for antigen presentation to T cells. Herpesviruses have been used to demonstrate these novel functions of autophagy, which previously has been primarily appreciated for its pro-survival role during starvation. In this review, we summarize recent findings how macroautophagy restricts herpesvirus infections directly, how macroautophagy and chaperone mediated autophagy contribute to herpesviral antigen presentation on MHC molecules, and which mechanisms herpesviruses have developed to interfere with these pathways. These studies suggest that herpesviruses significantly modulate autophagy to escape from its functions in innate and adaptive immunity.
Highlights
Mammalian cells use primarily two proteolytic systems to catabolise intra- and extracellular material for energy and macromolecular building block generation
This study clearly demonstrates that macroautophagy plays an important role in the ability of dendritic cells (DCs) to process and present antigens to CD4+ T cells
Neurovirulence was reduced in immunocompetent mice, a result suggesting that by binding Atg6/Beclin-1 and inhibiting macroautophagy, ICP34.5 interferes with the adaptive immune response to HSV. This was shown to be the case, with mice infected with the mutant virus making much larger HSV-1 specific CD4+ T cell responses relative to mice infected with a control virus [40]
Summary
Mammalian cells use primarily two proteolytic systems to catabolise intra- and extracellular material for energy and macromolecular building block generation. Herpesvirus antigen processing for MHC presentation by macroautophagy As described above, macroautophagy clearly plays an important role in the control of herpesvirus infection in vivo, possibly by orchestrating adaptive immunity in addition to just innately degrading pathogens. Along these lines, macroautophagy has been shown to influence the adaptive immune response towards herpesviruses. This was shown to be the case, with mice infected with the mutant virus (unable to inhibit macroautophagy) making much larger HSV-1 specific CD4+ T cell responses relative to mice infected with a control virus [40] These studies suggest that macroautophagy enhances CD4+ T cell immunity in vivo by assisting viral antigen presentation on MHC class II molecules. With the exception of HSV-1, which suppresses macroautophagy to enhance its replication and pathogenesis, the role of macroautophagy in the life cycle of other herpesviruses still needs to be further elucidated
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