SARS-CoV-2 Nsp1 protein binds the mRNA export receptor NXF1-NXT1 to inhibit nuclear export of mRNAs and promote infection. 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.
【초록키워드】 SARS-CoV-2, Antiviral, SARS-COV-2 infection, Infection, docking, Protein, outbreak, mRNA, nsp1, receptor, respiratory, virulence, mechanism, binding, host gene expression, mRNAs, virulence factor, nuclear pore, Messenger RNA, acute respiratory syndrome, infected cells, complex, nucleus, viral-host interaction, nuclear, inhibitory, cellular mRNAs, mRNA export, NXF1, NXT1, Host, Prevent, bind, responsible, caused, involved, inhibit, interact, promote, retained, Increased, cellular mRNA, mRNA export adaptor, the SARS-CoV-2, 【제목키워드】 SARS-CoV-2, Protein, host gene expression, inhibit, disrupt,