The Intertwined Life Cycles of Enterovirus and Autophagy

ABSTRACT

Enteroviruses (EVs) are the most common human pathogens worldwide. Recent international outbreaks in North America and South East Asia have emphasized the need for more effective anti-viral therapies. As obligate parasites, EVs rely on the host cellular machinery for effective viral propagation. Accumulating evidence has indicated that EVs subvert and disrupt the cellular autophagy pathway to facilitate productive infection, and consequently leading to host pathogenesis. Given that defective autophagy is a common factor in various human diseases, including neurodegeneration, cardiomyopathy, and metabolic disorders, a clear understanding of the relationship between EV infection and autophagy is warranted. In this review, we highlight recent advances in understanding the molecular mechanisms by which EVs exploit the autophagy pathway during different steps of viral life cycle, from entry, replication, and maturation to release. We also provide an overview of recent progress in EV subversion of the autophagy for immune evasion.

KEYWORDS:

• Enterovirus
• autophagy
• autophagosome
• amphisome
• lysosome
• non-lytic release
• virophagy
• immune evasion
• secretory autophagy

Acknowledgments

This work was supported by the Natural Sciences and Engineering Research Council (RGPIN-2016-03811), the Canadian Institutes of Health Research (PJT 159546), and the Heart & Stroke Foundation of Canada (G-16-00013800 and G-18-0022051). YM is the recipient of a four-year PhD Fellowship from the University of British Columbia and a Doctoral Fellowship from the ALS Canada-Brain Canada.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Canadian Institutes of Health Research [PJT159546];Heart and Stroke Foundation of Canada [G-16-00013800];Heart and Stroke Foundation of Canada [G-18-0022051];Natural Sciences and Engineering Research Council of Canada [RGPIN-2016-03811].