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Viruses and autophagy: bend, but don’t break

Nature Reviews Microbiology volume 22, pages 309–321 (2024)Cite this article

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Abstract

Autophagy is a constitutive cellular process of degradation required to maintain homeostasis and turn over spent organelles and aggregated proteins. For some viruses, the process can be antiviral, degrading viral proteins or virions themselves. For many other viruses, the induction of the autophagic process provides a benefit and promotes viral replication. In this Review, we survey the roles that the autophagic pathway plays in the replication of viruses. Most viruses that benefit from autophagic induction block autophagic degradation, which is a ‘bend, but don’t break’ strategy initiating but limiting a potentially antiviral response. In almost all cases, it is other effects of the redirected autophagic machinery that benefit these viruses. This rapid mechanism to generate small double-membraned vesicles can be usurped to shape membranes for viral genome replication and virion maturation. However, data suggest that autophagic maintenance of cellular homeostasis is crucial for the initiation of infection, as viruses have evolved to replicate in normal, healthy cells. Inhibition of autophagic degradation is important once infection has initiated. Although true degradative autophagy is probably a negative for most viruses, initiating nondegradative autophagic membranes benefits a wide variety of viruses.

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Fig. 1: Overview of the autophagic pathway.
Fig. 2: Autophagic induction and cargo capture.
Fig. 3: Regulation of autophagic flux.
Fig. 4: Viral interactions with the autophagic signalling pathway.
Fig. 5: Viral inhibition of autophagic cargo loading.
Fig. 6: Viral inhibition of autophagic flux.

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Acknowledgements

The authors thank the members of the Jackson, Frieman and Coughlan labs for weekly discussion sessions and M. Patricia (2017) for inspiring the title. This work was funded by National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) grants R01AI141359 and R01AI104928 to W.T.J. The authors apologize to any authors whose work was missed or given short mention because of space limitations.

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    Alagie Jassey & William T. Jackson

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Jassey, A., Jackson, W.T. Viruses and autophagy: bend, but don’t break. Nat Rev Microbiol 22, 309–321 (2024). https://doi.org/10.1038/s41579-023-00995-y

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