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Cellular Sensors and Viral Countermeasures: A Molecular Arms Race between Host and SARS-CoV-2.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic that has caused disastrous effects on the society and human health globally. SARS-CoV-2 is a sarbecovirus in the Coronaviridae family with a positive-sense single-stranded RNA genome. It mainly replicates in the cytoplasm and viral components including RNAs and proteins can be sensed by pattern recognition receptors including toll-like receptors (TLRs), RIG-I-like receptors (RLRs), and NOD-like receptors (NLRs) that regulate the host innate and adaptive immune responses. On the other hand, the SARS-CoV-2 genome encodes multiple proteins that can antagonize the host immune response to facilitate viral replication. In this review, we discuss the current knowledge on host sensors and viral countermeasures against host innate immune response to provide insights on virus-host interactions and novel approaches to modulate host inflammation and antiviral responses.

SUBMITTER: Sun H

PROVIDER: S-EPMC9962416 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Cellular Sensors and Viral Countermeasures: A Molecular Arms Race between Host and SARS-CoV-2.

Sun Haoran H Chan Jasper Fuk-Woo JF Yuan Shuofeng S

Viruses 20230126 2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic that has caused disastrous effects on the society and human health globally. SARS-CoV-2 is a sarbecovirus in the <i>Coronaviridae</i> family with a positive-sense single-stranded RNA genome. It mainly replicates in the cytoplasm and viral components including RNAs and proteins can be sensed by pattern recognition receptors including toll-like receptors (TLRs), R ...[more]

PMID: 36851564

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Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the largest RNA genome, approximately 30 kb, among RNA viruses. The DDX DEAD box RNA helicase is a multifunctional protein involved in all aspects of RNA metabolism. Therefore, host RNA helicases may regulate and maintain such a large viral RNA genome. In this study, I investigated the potential role of several host cellular RNA helicases in SARS-CoV-2 infection. Notably, DDX21 knockdown markedly accumulated intracellular viral RNA and viral production, as well as viral infectivity of SARS-CoV-2, indicating that DDX21 strongly restricts the SARS-CoV-2 infection. In addition, MOV10 RNA helicase also suppressed the SARS-CoV-2 infection. In contrast, DDX1, DDX5, and DDX6 RNA helicases were required for SARS-CoV-2 replication. Indeed, SARS-CoV-2 infection dispersed the P-body formation of DDX6 and MOV10 RNA helicases as well as XRN1 exonuclease, while the viral infection did not induce stress granule formation. Accordingly, the SARS-CoV-2 nucleocapsid (N) protein interacted with DDX1, DDX3, DDX5, DDX6, DDX21, and MOV10 and disrupted the P-body formation, suggesting that SARS-CoV-2 N hijacks DDX6 to carry out viral replication. Conversely, DDX21 and MOV10 restricted SARS-CoV-2 infection through an interaction of SARS-CoV-2 N with host cellular RNA helicases. Altogether, host cellular RNA helicases seem to regulate the SARS-CoV-2 infection. IMPORTANCE SARS-CoV-2 has a large RNA genome, of approximately 30 kb. To regulate and maintain such a large viral RNA genome, host RNA helicases may be involved in SARS-CoV-2 replication. In this study, I have demonstrated that DDX21 and MOV10 RNA helicases limit viral infection and replication. In contrast, DDX1, DDX5, and DDX6 are required for SARS-CoV-2 infection. Interestingly, SARS-CoV-2 infection disrupted P-body formation and attenuated or suppressed stress granule formation. Thus, SARS-CoV-2 seems to hijack host cellular RNA helicases to play a proviral role by facilitating viral infection and replication and by suppressing the host innate immune system.

Dataset Information

Cellular Sensors and Viral Countermeasures: A Molecular Arms Race between Host and SARS-CoV-2.

Publications

Cellular Sensors and Viral Countermeasures: A Molecular Arms Race between Host and SARS-CoV-2.

Similar Datasets

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