Nsp1 protein of SARS-CoV-2 disrupts the mRNA export machinery to inhibit host gene expression.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33547084.
- Also identified by DOI 10.1126/sciadv.abe7386 and PMC identifier 7864571.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The ongoing unprecedented severe acute respiratory syndrome caused by the SARS-CoV-2 outbreak worldwide has highlighted the need for understanding viral-host interactions involved in mechanisms of virulence. Here, we show that the virulence factor Nsp1 protein of SARS-CoV-2 interacts with the host messenger RNA (mRNA) export receptor heterodimer NXF1-NXT1, which is responsible for nuclear export of cellular mRNAs. Nsp1 prevents proper binding of NXF1 to mRNA export adaptors and NXF1 docking at the nuclear pore complex. As a result, a significant number of cellular mRNAs are retained in the nucleus during infection. Increased levels of NXF1 rescues the Nsp1-mediated mRNA export block and inhibits SARS-CoV-2 infection. Thus, antagonizing the Nsp1 inhibitory function on mRNA export may represent a strategy to restoring proper antiviral host gene expression in infected cells.
Medical subject headings
- COVID-19
- Gene Expression
- Host Microbial Interactions
- RNA, Messenger
- SARS-CoV-2
- Viral Nonstructural Proteins
- Virulence Factors