SARS-CoV-2 promote autophagy to suppress type I interferon response

Hui, Xianfeng; Zhang, Linliang; Cao, Lei; Huang, Kun; Zhao, Ya; Zhang, Yufei; Chen, Xi; Lin, Xian; Chen, Mingzhou; Jin, Meilin

doi:10.1038/s41392-021-00574-8

Cited by 62 publications

(54 citation statements)

References 6 publications

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“…In agreement with the previous study, SARS-CoV-2 infection did stimulate autophagy (specifically, mitophagy), as judged by an increased number of LC3-positive autophagosomes and elevated LC3-II levels, but decreased levels of the mitochondrial markers TOMM20 and translocase of inner mitochondrial membrane 23 (TIMM23), in Vero E6, human hepatocellular carcinoma (Huh-7), and colorectal adenocarcinoma (Caco-2) cells [30]. Interestingly, Jin and colleagues identified the viral membrane (M) protein behind these effects because the expression of a single M protein could recapitulate them, in addition to decreased SQSTM1 levels.…”

Section: Protein M Promotes Mitophagysupporting

confidence: 92%

“…Recently, several excellent reviews have been published on this subject [47][48][49][50][51]. As mentioned above, in some cases, the antiviral effects of the drugs correlate with their ability to inhibit autophagy [30,31,46]. However, in other cases, the antiviral activities of the drugs are linked to the upregulation of autophagy (e.g., niclosamide induces autophagosome formation, similar to MERS-CoV itself, but it also overcomes a block of the autophagosome-lysosome fusion caused by MERS-CoV, resulting in a spectacular clearance of the virus by autophagy [45]).…”

Section: Discussionmentioning

confidence: 99%

“…Notably, both M protein expression and SARS-CoV-2 infection cause re-localization of LC3 to mitochondria, indicating that this might be a physiologically relevant mechanism. Moreover, this mechanism may have important immunological consequences as M protein (but, to a lesser extent, M without LIR) affects transcriptional activation of interferon beta 1 (IFNB1) via DExD/H-box helicase 58 (DDX58; also known as RIG-I) and mitochondrial antiviral signaling protein (MAVS) [30]. Additionally, blocking autophagy with the phosphatidylinositol 3-kinase inhibitors, 3-methyladenine and wortmannin, or specific block of phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3; also known as VPS34) with Vps34-IN1 inhibitor, limits SARS-CoV-2 replication in Vero E6, Huh-7, and Caco-2 cells, and human ex vivo lung tissue culture [30,31], suggesting that the M protein-induced mitophagy might play a role in viral replication.…”

Section: Protein M Promotes Mitophagymentioning

confidence: 99%

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The Molecular Interplay between Human Coronaviruses and Autophagy

Shroff

Nazarko

2021

Cells

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Coronavirus disease 2019 (COVID-19), caused by a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has instantaneously emerged as a worldwide pandemic. However, humans encountered other coronaviruses in the past, and they caused a broad range of symptoms, from mild to life-threatening, depending on the virus and immunocompetence of the host. Most human coronaviruses interact with the proteins and/or double-membrane vesicles of autophagy, the membrane trafficking pathway that degrades and recycles the intracellular protein aggregates, organelles, and pathogens, including viruses. However, coronaviruses often neutralize and hijack this pathway to complete their life cycle. In this review, we discuss the interactions of human coronaviruses and autophagy, including recent data from SARS-CoV-2-related studies. Some of these interactions (for example, viral block of the autophagosome–lysosome fusion), while being conserved across multiple coronaviruses, are accomplished via different molecular mechanisms. Therefore, it is important to understand the molecular interplay between human coronaviruses and autophagy for developing efficient therapies against coronaviral diseases.

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Section: Protein M Promotes Mitophagysupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Protein M Promotes Mitophagymentioning

confidence: 99%

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The Molecular Interplay between Human Coronaviruses and Autophagy

Shroff

Nazarko

2021

Cells

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“…Autophagy may help SARS-CoV-2 escape from the host immune response. One recent study determined that overexpressing one of the SARS-CoV-2 main structural proteins, M, induces mitochondria degradation through mitophagy to block innate immunity signaling and inhibit the type I IFN (interferon) response [ 347 ]. Additionally, ORF8 of SARS-CoV-2 mediates the degradation of major histocompability complex class Ι (MHC-I) through autophagy [ 348 ], while the specific mechanism and the receptor for this selective autophagic degradation remain unknown.…”

Section: Autophagy and Infectious Diseasesmentioning

confidence: 99%

The Emerging Roles of Autophagy in Human Diseases

Lei

Klionsky

2021

Biomedicines

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Autophagy, a process of cellular self-digestion, delivers intracellular components including superfluous and dysfunctional proteins and organelles to the lysosome for degradation and recycling and is important to maintain cellular homeostasis. In recent decades, autophagy has been found to help fight against a variety of human diseases, but, at the same time, autophagy can also promote the procession of certain pathologies, which makes the connection between autophagy and diseases complex but interesting. In this review, we summarize the advances in understanding the roles of autophagy in human diseases and the therapeutic methods targeting autophagy and discuss some of the remaining questions in this field, focusing on cancer, neurodegenerative diseases, infectious diseases and metabolic disorders.

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“…In the airways, type I IFNs play important roles in protecting from the spread of respiratory viruses and are critical in initiating inflammatory responses. Although SARS-CoV-2 is sensitive to IFN-I [537] and all IFN types can inhibit its replication in a dosedependent manner [568], recent studies have reported a delayed induction of the IFN-I response during SARS-CoV-2 infection [569,570], partly driven by SARS-CoV-2-promoted autophagy [571]. This delayed IFN induction is a prominent feature of COVID-19 and distinguishes SARS-CoV-2 infection from other viral infections such as SARS-CoV-1 and influenza A virus (IAV) [68,443].…”

Section: Interferon Responsementioning

confidence: 99%

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

Duerr¹,

Jimenez²,

Dittmann³

2021

Preprint

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SARS-CoV-2 and HIV are zoonotic viruses that rapidly reached pandemic scale causing global losses and fear. The COVID-19 and AIDS pandemics ignited massive efforts worldwide to develop antiviral strategies and characterize viral architectures, biological and immunological properties, and clinical outcomes. Although both viruses have a comparable appearance as enveloped viruses with positive-stranded RNA and envelope spikes mediating cellular entry, the entry process, downstream biological and immunological pathways, clinical outcomes, and disease courses are strikingly different. This review provides a systemic comparison of both viruses’ structural and functional characteristics delineating their distinct strategies for efficient spread.

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SARS-CoV-2 promote autophagy to suppress type I interferon response

Cited by 62 publications

References 6 publications

The Molecular Interplay between Human Coronaviruses and Autophagy

The Molecular Interplay between Human Coronaviruses and Autophagy

The Emerging Roles of Autophagy in Human Diseases

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

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