Coronavirus Usurps the Autophagy-Lysosome Pathway and Induces Membranes Rearrangement for Infection and Pathogenesis.

Haowei Liang,Hai Liao,Shun Li,Dan Luo

doi:10.3389/fmicb.2022.846543

Haowei Liang, Hai Liao + Show 2 more

Open Access

https://doi.org/10.3389/fmicb.2022.846543

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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.

Highlights

At the beginning of the 21st century, we have witnessed the outbreak of three types of diseases by coronavirus (CoV) infection, which are severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19)
The specific process of CoV infection of host cells is not yet completely clear, according to previous studies, the infection cycle of CoVs is divided into several steps: attachment and membrane fusion, uncoating of the viral genome, translation of open-reading frames (ORFs) and non-structural proteins (NSPs), formation of double-membrane vesicles (DMVs), genome transcription and replication, and virion release (Fung and Liu, 2019)
We suggest that autophagy-derived DMVs and ERderived DMVs are two different important pathways of DMV production

Summary

INTRODUCTION

At the beginning of the 21st century, we have witnessed the outbreak of three types of diseases by coronavirus (CoV) infection, which are severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19). CoVs can hijack autophagy initiation to form unique DMVs. On the other hand, CoVs induce ER-derived DMVs independent of the autophagic pathway by hijacking host cell ER-associated degradation (ERAD) machinery (Konno et al, 2020). NSP6 and the PLP2 domain of NSP3 of SARS-CoV and MERS-CoV promote the degradation of Beclin through the activation of SKP2 via the AKT signaling pathway, which inhibits vesicle nucleation and autophagosome formation (Gassen et al, 2019) These non-nucleation phagophores and omegasomes self-use to autophagy-derived. SARS-CoV-2 NSP4 and NSP6 induce ER-derived DMVs independent of the autophagic pathway by hijacking the host cell ERAD machinery (Muscolino et al, 2020). CoVs induce ER-derived DMVs independently by hijacking ERAD machinery (Figure 1)

CORONAVIRUSES USURP HOST CLEARANCE BY INTERCEPTING AUTOPHAGY FLUX

Findings

DISCUSSION