Journal
SCIENCE ADVANCES
Volume 7, Issue 6, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abe7386
Keywords
-
Categories
Funding
- NIH [R01 AI154635]
- Career Enhancement Program Award SPORE [P50 CA070907]
- Mary Kay Foundation International Postdoctoral Scholar Fellowship
- Canadian Institutes of Health Research [FRN:156030]
- CRIP (Center for Research on Influenza Pathogenesis), an NIAID [HHSN272201400008C]
- DARPA [HR0011-19-2-0020]
- Open Philanthropy Project [2020-215611 (5384)]
- Lung Cancer SPORE [P50 CA070907]
- CPRIT [RP180725]
- [R35GM133743]
- [U54 CA260560]
Ask authors/readers for more resources
The research shows that the virulence factor Nsp1 protein of SARS-CoV-2 interacts with the host messenger RNA (mRNA) export receptor heterodimer NXF1-NXT1, leading to retention of cellular mRNAs in the nucleus during infection. Increasing levels of NXF1 can rescue the Nsp1-mediated mRNA export block and inhibit SARS-CoV-2 infection. Antagonizing the inhibitory function of Nsp1 on mRNA export may represent a strategy to restore proper antiviral host gene expression in infected cells.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available