Nsp1 protein of SARS-CoV-2 disrupts the mRNA export machinery to inhibit host gene expression

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 m...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Ke, Miorin, Lisa, Makio, Tadashi, Dehghan, Ishmael, Gao, Shengyan, Xie, Yihu, Zhong, Hualin, Esparza, Matthew, Kehrer, Thomas, Kumar, Anil, Hobman, Tom C., Ptak, Christopher, Gao, Boning, Minna, John D., Chen, Zhijian, García-Sastre, Adolfo, Ren, Yi, Wozniak, Richard W., Fontoura, Beatriz M.A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
Materias:
Research Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864571/
https://www.ncbi.nlm.nih.gov/pubmed/33547084
http://dx.doi.org/10.1126/sciadv.abe7386
Descripción
Sumario: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.

Ejemplares similares