The respiratory syncytial virus matrix protein possesses a Crm1-mediated nuclear export mechanism

Reena Ghildyal, Adeline Ho, Manisha Dias, Lydia Soegiyono, Philip G Bardin, Kim C Tran, Michael N Teng, David Andrew Jans

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The respiratory syncytial virus (RSV) matrix (M) protein is localized in the nucleus of infected cells early in infection, but is mostly cytoplasmic late in infection. We have previously shown that M localizes in the nucleus through the action of the importin beta1 nuclear import receptor. Here we establish for the first time that M s ability to shuttle to the cytoplasm is due to the action of the nuclear export receptor Crm1, as shown in infected cells, and in cells transfected to express green fluorescent protein (GFP)-M fusion proteins. Specific inhibition of Crm1-mediated nuclear export by leptomycin B increased M nuclear accumulation. Analysis of truncated and point-mutated M derivatives indicated that Crm1-dependent nuclear export of M is attributable to a nuclear export signal (NES) within residues 194-206. Importantly, inhibition of M nuclear export resulted in reduced virus production, and a recombinant RSV carrying a mutated NES could not be rescued by reverse genetics. That this is likely to be due to the inability of a nuclear export deficient M to localize to regions of virus assembly is indicated by the fact that a nuclear export deficient GFP-M fails to localize to regions of virus assembly when expressed in cells infected with wild type RSV. Together, our data suggest that Crm1-dependent nuclear export of M is central to RSV infection, representing the first report of such a mechanism for a paramyxovirus M protein, and with important implications for related paramyxoviruses.
Original languageEnglish
Pages (from-to)5353 - 5362
Number of pages10
JournalJournal of Virology
Issue number11
Publication statusPublished - 2009

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