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  • Review Article
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Autophagy during viral infection — a double-edged sword

Nature Reviews Microbiology volume 16, pages 341–354 (2018)Cite this article

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Abstract

Autophagy is a powerful tool that host cells use to defend against viral infection. Double-membrane vesicles, termed autophagosomes, deliver trapped viral cargo to the lysosome for degradation. Specifically, autophagy initiates an innate immune response by cooperating with pattern recognition receptor signalling to induce interferon production. It also selectively degrades immune components associated with viral particles. Following degradation, autophagy coordinates adaptive immunity by delivering virus-derived antigens for presentation to T lymphocytes. However, in an ongoing evolutionary arms race, viruses have acquired the potent ability to hijack and subvert autophagy for their benefit. In this Review, we focus on the key regulatory steps during viral infection in which autophagy is involved and discuss the specific molecular mechanisms that diverse viruses use to repurpose autophagy for their life cycle and pathogenesis.

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Fig. 1: Pattern recognition receptors and autophagy.
Fig. 2: Autophagy-mediated antiviral immune responses.
Fig. 3: Viral manipulation of autophagy.
Fig. 4: Viral manipulation of lipophagy and exocytosis.

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Acknowledgements

During the preparation of this Review article, the authors were supported by grants from the US National Institutes of Health (CA200422, CA180779, DE023926, AI073099, AI116585 and AI129496) and the Fletcher Jones Foundation. The authors sincerely apologize for not being able to cite all papers related to this topic owing to space limitations.

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Authors and Affiliations

  1. Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Zilkha Neurogenetic Institute, Los Angeles, CA, USA

    Younho Choi, James W. Bowman & Jae U. Jung

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  1. Younho Choi
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  2. James W. Bowman
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Y.C. and J.U.J. substantially contributed to the discussion of content. All authors wrote the article and reviewed and edited the manuscript before submission.

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Correspondence to Jae U. Jung.

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Glossary

Multivesicular bodies

(MVBs). A specialized subset of endosomes that contain membrane-bound intraluminal vesicles.

Unfolded protein response

(UPR). A cellular stress response activated in response to an accumulation of unfolded or aggregated proteins in the endoplasmic reticulum.

Type I interferon

(IFN). A subset of interferons, including IFNα, IFNβ and IFNω, that have potent antiviral roles by binding to a common receptor (interferon receptor (IFNAR)).

Plasmacytoid dendritic cells

(pDCs). A subset of dendritic cells that are distinct from conventional dendritic cells and that produce large amounts of interferon.

IFN-stimulated genes

(ISGs). A subset of genes induced by the activation of the interferon receptor-mediated JAK–STAT pathway.

E3-ubiquitin ligase

An enzyme catalysing transfer of ubiquitin from the activated site of an E2 enzyme to a primary amine on a lysine side chain or amino terminus of a protein.

Restriction factor

An antiviral protein that is produced in the host and blocks viral replication.

Langerhans cells

Immune cells found in the epidermis that function as antigen-presenting cells that bind antigens entering through the skin.

Crohn’s disease

A chronic inflammatory disease of the gastrointestinal tract.

Puncta

A structural marker that is involved in autophagosome formation by the dynamic process of LC3 association.

LC3 lipidation

A conjugation of phosphatidylethanolamine (PE) to LC3 to form LC3–PE, which is recruited to autophagosomal membranes.

ER-associated degradation

(ERAD). A process through which misfolded proteins are transported from the endoplasmic reticulum to the cytoplasm for proteasomal degradation.

SNAP receptor

(SNARE). A key component of the cellular membrane fusion machinery that mediates vesicular fusion events in autophagosome–lysosome fusion.

Lipid raft

A small heterogeneous cellular compartment enriched with sphingolipids and cholesterols.

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Choi, Y., Bowman, J.W. & Jung, J.U. Autophagy during viral infection — a double-edged sword. Nat Rev Microbiol 16, 341–354 (2018). https://doi.org/10.1038/s41579-018-0003-6

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