Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Nsp1 proteins of human coronaviruses HCoV-OC43 and SARS-CoV2 inhibit stress granule formation Stress granules (SGs) are cytoplasmic condensates that often form as part of the cellular antiviral response. Despite the growing interest in understanding the interplay between SGs and other biological condensates and viral replication, the role of SG formation during coronavirus infection remains poorly understood. Several proteins from different coronaviruses have been shown to suppress SG formation upon overexpression, but there are only a handful of studies analyzing SG formation in coronavirus- infected cells. To better understand SG inhibition by coronaviruses, we analyzed SG formation during infection with the human common cold coronavirus OC43 (HCoV-OC43) and the highly pathogenic SARS-CoV2. We did not observe SG induction in infected cells and both viruses inhibited eukaryotic translation initiation factor 2 (eIF2) phosphorylation and SG formation induced by exogenous stress (e.g. sodium arsenite treatment). Furthermore, in SARS-CoV2 infected cells we observed a sharp decrease in the levels of SG-nucleating protein G3BP1. Ectopic overexpression of nucleocapsid (N) and non-structural protein 1 (Nsp1) from both HCoV-OC43 and SARS-CoV-2 inhibited SG formation. The Nsp1 proteins of both viruses inhibited arsenite-induced eIF2 phosphorylation, and the Nsp1 of SARS- CoV2 alone was sufficient to cause decrease in G3BP1 levels. This phenotype was dependent on the depletion of cytoplasmic mRNA mediated by Nsp1 and associated with nuclear retention of the SG- nucleating protein TIAR. To test the role of G3BP1 in coronavirus replication, we infected cells overexpressing EGFP-tagged G3BP1 with HCoV-OC43 and observed a significant decrease in infection compared to control cells expressing EGFP. The antiviral role of G3BP1 and the existence of multiple SG suppression mechanisms that are conserved between HCoV-OC43 and SARS-CoV2 suggest that SG formation may represent an important antiviral host defense that coronaviruses target to ensure efficient replication.

Author SummaryHost cells possess many mechanisms that can detect viral infections and trigger defense programs to suppress viral replication and spread. One of such antiviral mechanisms is the formation of stress granules - large aggregates of RNA and proteins that sequester viral components and cellular factors needed by the virus to replicate. Because of this threat, viruses evolved specific mechanisms that prevent stress granule formation. Understanding these mechanisms can reveal potential targets for therapies that would disable viral inhibition of stress granules and render cells resistant to infection. In this study we analyzed inhibition of stress granules by two human coronaviruses: the common cold coronavirus OC43 and the pandemic SARS-CoV2. We have demonstrated that these viruses employ at least two proteins - nucleocapsid protein (N) and the non-structural protein 1 (Nsp1) to suppress stress granules. These proteins act through distinct complementary mechanisms to ensure successful virus replication. Because both OC43 and SARS-CoV2 each dedicate more than one gene product to inhibit stress granule formation, our work suggests that viral disarming of stress granule responses is central for a productive infection.
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The categories of this paper are: scientific
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The categories of this paper are: education
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The categories of this paper are: bioinformatics
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The categories of this paper are: cognition
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The categories of this paper are: neuroscience
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The categories of this paper are: communication
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The categories of this paper are: synthetic
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The categories of this paper are: epidemiology
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The categories of this paper are: genomics
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The categories of this paper are: systems
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The categories of this paper are: and
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The categories of this paper are: ecology
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The categories of this paper are: developmental
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The categories of this paper are: biology
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The categories of this paper are: toxicology
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The categories of this paper are: cancer