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

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

doi:10.1038/ni.1720

Cited by 410 publications

(429 citation statements)

References 43 publications

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“…A pertinent example is the role of autophagy in facilitating MHCI presentation by herpes simplex virus 1 (HSV-1) infected macrophages, 8-12 h after infection (English et al, 2009). At these time points, treatment of HSV-1 infected macrophages with bafilomycin A (an inhibitor of lysosomal acidification), 3-MA or knockdown of Atg5, im-pairs HSV-1 glycoprotein B (gB)-specific CD8 + T cell activation, indicating that at this stage of infection both autophagosomes and lysosomal degradation are required for gB MHCI antigen presentation (English et al, 2009). Using fluorescence and electron microscopy, LC3+ autophagosomes are observed to originate from the nuclear envelope containing HSV-1 particles (English et al, 2009).…”

Section: Autophagy In Classical Mhc Class I Antigen Presentationmentioning

confidence: 99%

“…At these time points, treatment of HSV-1 infected macrophages with bafilomycin A (an inhibitor of lysosomal acidification), 3-MA or knockdown of Atg5, im-pairs HSV-1 glycoprotein B (gB)-specific CD8 + T cell activation, indicating that at this stage of infection both autophagosomes and lysosomal degradation are required for gB MHCI antigen presentation (English et al, 2009). Using fluorescence and electron microscopy, LC3+ autophagosomes are observed to originate from the nuclear envelope containing HSV-1 particles (English et al, 2009). The authors suggest that gB processing begins in the autophagosome after which gB peptides escape to the cytosol for further processing by the proteasome and entry into the MHCI antigen presentation pathway.…”

Section: Autophagy In Classical Mhc Class I Antigen Presentationmentioning

confidence: 99%

“…Notably, a stimulatory role for IFNγ in autophagy regulation is not always the case. Treatment of HSV-1 infected macrophages with interleukin 1β (IL-1β), but not IFNγ, increases autophagy and improves gB-specific CD8 + T cell responses (English et al, 2009). Some cytokines can act as inhibitors of autophagy.…”

Section: Regulation Of Autophagymentioning

confidence: 99%

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Intersection of autophagy with pathways of antigen presentation

Patterson

Mintern

2012

Protein Cell

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Traditionally, macroautophagy (autophagy) is viewed as a pathway of cell survival. Autophagy ensures the elimination of damaged or unwanted cytosolic components and provides a source of cellular nutrients during periods of stress. Interestingly, autophagy can also directly intersect with, and impact, other major pathways of cellular function. Here, we will review the contribution of autophagy to pathways of antigen presentation. The autophagy machinery acts to modulate both MHCI and MHCII antigen presentation. As such autophagy is an important participant in pathways that elicit host cell immunity and the elimination of infectious pathogens.

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Section: Autophagy In Classical Mhc Class I Antigen Presentationmentioning

confidence: 99%

Section: Autophagy In Classical Mhc Class I Antigen Presentationmentioning

confidence: 99%

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Intersection of autophagy with pathways of antigen presentation

Patterson

Mintern

2012

Protein Cell

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“…In autophagosome viral proteins undergo further processing by the proteasome for MHC presentation [37,38]. It has been shown that altered HSV-1 gene transfer to neuronal cells leads to the induction of MHC-I and MHC-II, which drives inflammatory effects characterized by the recruitment of activated T cells and macrophages [143].…”

Section: Altered Mhc Response During Viral Infectionmentioning

confidence: 99%

Immune Regulation and Evasion of Mammalian Host Cell Immunity During Viral Infection

et al. 2013

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The mammalian host immune system has wide array of defence mechanisms against viral infections. Depending on host immunity and the extent of viral persistence, either the host immune cells might clear/restrict the viral load and disease progression or the virus might evade host immunity by down regulating host immune effector response(s). Viral antigen processing and presentation in the host cells through major histocompatibility complex (MHC) elicit subsequent anti-viral effector T cell response(s). However, modulation of such response(s) might generate one of the important viral immune evasion strategies. Viral peptides are mostly generated by proteolytic cleavage in the cytosol of the infected host cells. CD8 ? T lymphocytes play critical role in the detection of viral infection by recognizing these peptides displayed at the plasma membrane by MHC-I molecules. The present review summarises the current knowledge on the regulation of mammalian host innate and adaptive immune components, which are operative in defence mechanisms against viral infections and the variety of strategies that viruses have evolved to escape host cell immunity. The understanding of viral immune evasion strategies is important for designing anti-viral immunotherapies.

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“…Both rough ER and the outer nuclear leaflet have been identified as autophagosome formation sites [13][14][15] , but these vesicles might also be generated at other places. Two ubiquitin-like systems are involved in autophagosome formation at these sites with Atg8 and Atg12 as the ubiquitin-like molecules at their center 16 .…”

Section: T Cells Detect Infected or Transformed Cells Via Antigen Prementioning

confidence: 99%

MHC presentation via autophagy and how viruses escape from it

Gannagé

Münz

2010

Semin Immunopathol

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T cells detect infected and transformed cells via antigen presentation by major histocompatibility complex (MHC) molecules on the cell surface. For T cell stimulation, these MHC molecules present fragments of proteins that are expressed or taken up by the cell. These fragments are generated by distinct proteolytic mechanisms for presentation on MHC class I molecules to cytotoxic CD8(+) and on MHC class II molecules to helper CD4(+) T cells. Proteasomes are primarily involved in MHC class I ligand and lysosomes, in MHC class II ligand generation. Autophagy delivers cytoplasmic material to lysosomes and, therefore, contributes to cytoplasmic antigen presentation by MHC class II molecules. In addition, it has been recently realized that this process also supports extracellular antigen processing for MHC class II presentation and cross-presentation on MHC class I molecules. Although the exact mechanisms for the regulation of these antigen processing pathways by autophagy are still unknown, recent studies, summarized in this review, suggest that they contribute to immune responses against infections and to maintain tolerance. Moreover, they are targeted by viruses for immune escape and could maybe be harnessed for immunotherapy. These fragments are generated by distinct proteolytic mechanisms for presentation on MHC class I molecules to cytotoxic CD8 + and on MHC class II molecules to helper CD4 + T cells.Proteasomes are primarily involved in MHC class I ligand, and lysosomes in MHC class II ligand generation. Autophagy delivers cytoplasmic material to lysosomes, and, therefore, contributes to cytoplasmic antigen presentation by MHC class II molecules. In addition, it has been recently realized that this process also supports extracellular antigen processing for MHC class II presentation and cross-presentation on MHC class I molecules. Although the exact mechanisms for the regulation of these antigen processing pathways by autophagy are still unknown, recent studies, summarized in this review, suggest that they contribute to immune responses against infections and to maintain tolerance. Moreover, they are targeted by viruses for immune escape, and could maybe be harnessed for immunotherapy. Gannage and Münz 3

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

Cited by 410 publications

References 43 publications

Intersection of autophagy with pathways of antigen presentation

Intersection of autophagy with pathways of antigen presentation

Immune Regulation and Evasion of Mammalian Host Cell Immunity During Viral Infection

MHC presentation via autophagy and how viruses escape from it

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