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Dissecting the mechanism of host shutoff by SARS coronavirus
Author(s) -
Nag Anita,
Gomez Garret G.
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.649.7
Subject(s) - nuclear pore , nucleoporin , biology , microbiology and biotechnology , gene expression , nucleolin , exoribonuclease , ribosome , coronavirus , rna , gene , cell nucleus , cytoplasm , nuclear transport , genetics , nucleolus , medicine , disease , covid-19 , pathology , infectious disease (medical specialty) , rnase p
Down regulation of host gene expression during viral infection, known as host shutoff, involves destabilization of host mRNA. Several viruses, including Kaposi's sarcoma virus, Epstein B virus, severe acute respiratory syndrome coronavirus (SARS CoV) and Middle Eastern respiratory syndrome coronavirus inhibit host gene expression by stalling the ribosome on mRNA and subsequently cleaving and degrading host mRNA. In SARS‐CoV, nsp1 is the key factor in virus‐induced down‐regulation of host gene expression. In infected cells, nsp1 engages in a multi‐pronged mechanism to inhibit host gene expression by binding to the 40S ribosomal subunit to stall further ribosome assembly and inducing endonucleolytic cleavage and degradation of host mRNAs. We identified a previously undetected mechanism by which nsp1 exploits the nuclear pore complex and disrupts nuclear‐cytoplasmic transport of biomolecules. Using quantitative proteomics we identified members of the nuclear pore complex from nsp1‐associated protein assembly. Expression of nsp1 in HEK cells disrupts Nup93 localization around the nuclear envelope without triggering proteolytic degradation of the protein while other nucleoporins and the nuclear lamina remain unperturbed, suggesting significant alteration of the nuclear pore complex in the presence of nsp1. Furthermore, Nup93 reconvenes to the nuclear pore when nsp1 is removed. Consistent with its role in host shutoff, nsp1 alters the nuclear‐cytoplasmic distribution of a RNA binding protein, nucleolin. Our results suggest that nsp1 alone can regulate multiple steps of gene expression including nuclear‐cytoplasmic transport. Support or Funding Information SC INBRE Bioinformatics Pilot Project AwardSCICU This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .