SARS coronavirus protein nsp1 disrupts localization of Nup93 from the nuclear pore complex.

Severe acute respiratory syndrome coronavirus nonstructural protein 1 (nsp1) is a key factor in virus-induced down-regulation of host gene expression. In infected cells， nsp1 engages in a multi-pronged mechanism to inhibit host gene expression by binding to the 40S ribosome to block the assembly of translationally competent ribosome， and then inducing endonucleolytic cleavage and the degradation of host mRNAs. Here， we report a previously undetected mechanism by which nsp1 exploits the nuclear pore complex and disrupts nuclear-cytoplasmic transport of biomolecules. We identified members of the nuclear pore complex from nsp1-associated protein assembly and found that expression of nsp1 in HEK cells disrupts Nup93 localization around the nuclear envelope without triggering proteolytic degradation， while the nuclear lamina remains unperturbed. Consistent with its role in host shutoff， nsp1 alters the nuclear-cytoplasmic distribution of a RNA binding protein， nucleolin. Our results suggest that nsp1， alone， can regulate multiple steps of gene expression including nuclear-cytoplasmic transport.