@article{62854eba2d8a415196ef67b9a3938f1b,
title = "Nsp1 protein of SARS-CoV-2 disrupts the mRNA export machinery to inhibit host gene expression",
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.",
author = "Ke Zhang and Lisa Miorin and Tadashi Makio and Ishmael Dehghan and Shengyan Gao and Yihu Xie and Hualin Zhong and Matthew Esparza and Thomas Kehrer and Anil Kumar and Hobman, {Tom C.} and Christopher Ptak and Boning Gao and Minna, {John D.} and Zhijian Chen and Adolfo Garc{\'i}a-Sastre and Yi Ren and Wozniak, {Richard W.} and Fontoura, {Beatriz M.A.}",
note = "Funding Information: This work was supported by NIH R01 AI154635 to B.M.A.F.; by a Career Enhancement Program Award SPORE P50 CA070907 to B.M.A.F.; by a U54 CA260560 Project 2 to A.G.-S., B.M.A.F., and J.D.M.; by a Mary Kay Foundation International Postdoctoral Scholar Fellowship to S.G.; by funding from the Canadian Institutes of Health Research (FRN:156030) to R.W.W.; by CRIP (Center for Research on Influenza Pathogenesis), an NIAID-funded Centers of Excellence for Influenza Research and Surveillance (CEIRS; contract no. HHSN272201400008C), by DARPA grant HR0011-19-2-0020, and by philanthropic donations from the JPB Foundation, the Open Philanthropy Project [research grant 2020-215611 (5384)], and anonymous donors to A.G.-S.; by R35GM133743 to Y.R.; by P50 CA070907 (Lung Cancer SPORE) to J.D.M; and by CPRIT (RP180725) to Z.C. Publisher Copyright: Copyright {\textcopyright} 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).",
year = "2021",
month = feb,
day = "5",
doi = "10.1126/sciadv.abe7386",
language = "English (US)",
volume = "7",
journal = "Science advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "6",
}