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Published on: October 28, 2019
Coronavirus Usurps the Autophagy-Lysosome Pathway and Induces Membranes Rearrangement for Infection and Pathogenesis
Haowei Liang1,2, Dan Luo1, Hai Liao2
1Department of Immunology, School of Basic Medical Sciences, Chengdu Medical College, Chengdu, China.
Abstract:
Autophagy is a crucial and conserved homeostatic mechanism for early defense against viral infections. Recent studies indicate that coronaviruses (CoVs) have evolved various strategies to evade the autophagy-lysosome pathway. In this minireview, we describe the source of double-membrane vesicles during CoV infection, which creates a microenvironment that promotes viral RNA replication and virion synthesis and protects the viral genome from detection by the host. Firstly, CoVs hijack autophagy initiation through non-structural proteins and open-reading frames, leading to the use of non-nucleated phagophores and omegasomes for autophagy-derived double-membrane vesicles. Contrastingly, membrane rearrangement by hijacking ER-associated degradation machinery to form ER-derived double-membrane vesicles independent from the typical autophagy process is another important routine for the production of double-membrane vesicles. Furthermore, we summarize the molecular mechanisms by which CoV non-structural proteins and open-reading frames are used to intercept autophagic flux and thereby evade host clearance and innate immunity. A comprehensive understanding of the above mechanisms may contribute to developing novel therapies and clinical drugs against coronavirus disease 2019 (COVID-19) in the future.
Insights
Coronaviruses (CoVs) evade host defenses by hijacking the autophagy pathway to create protective viral replication sites. Understanding these evasion strategies is key to developing new COVID-19 therapies.
Area of Science:
- Virology
- Cellular Biology
- Immunology
Background:
- Autophagy is a critical cellular defense mechanism against viral infections.
- Coronaviruses (CoVs) have developed sophisticated strategies to subvert the autophagy-lysosome pathway.
- Understanding CoV-autophagy interactions is crucial for combating viral diseases.
Purpose of the Study:
- To review the origins of double-membrane vesicles (DMVs) during CoV infection.
- To elucidate the molecular mechanisms by which CoVs manipulate autophagy.
- To highlight the implications for developing novel antiviral therapies.
Main Methods:
- Review of existing literature on CoV-autophagy interactions.
- Analysis of viral non-structural proteins and open-reading frames involved in autophagy manipulation.
- Examination of host-pathogen interactions at the molecular level.
Main Results:
- CoVs utilize autophagy-derived vesicles (phagophores, omegasomes) and ER-derived vesicles for replication.
- Viral proteins hijack autophagy initiation and intercept autophagic flux.
- These mechanisms protect viral RNA and evade host immune detection.
Conclusions:
- CoVs exploit cellular machinery to establish replication niches and evade immune responses.
- Targeting CoV-hijacked autophagy pathways offers potential therapeutic strategies against CoVs, including SARS-CoV-2.
- Further research into these mechanisms can inform the development of effective COVID-19 treatments.
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