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A Nuclear Export Signal in the Matrix Protein of Influenza A Virus Is Required for the Efficient Virus Replication

tetano

Editor, Senior Moderator
J Virol. 2012 Feb 15. [Epub ahead of print]
A Nuclear Export Signal in the Matrix Protein of Influenza A Virus Is Required for the Efficient Virus Replication.
Cao S, Liu X, Yu M, Li J, Jia X, Bi Y, Sun L, Gao GF, Liu W.
Source

Center for Molecular Virology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Abstract

Influenza A virus matrix 1 protein (M1) shuttles between the cytoplasm and the nucleus during the viral life cycle and plays an important role in the replication, assembly, and budding of viruses. Here, a leucine-rich nuclear export signal (NES) was identified specifically for the nuclear export of the M1 protein. The predicted NES, designated as Flu-A-M1 NES, is highly conserved among all sequences from the influenza A virus subtype, but no similar NES motifs are found in the M1 sequences of influenza B or C viruses. The biological function of the Flu-A-M1 NES was demonstrated by its ability to translocate an EGFP-NES fusion protein from the nucleus to the cytoplasm in transfected cells compared to the even nuclear and cytoplasmic distribution of EGFP. The translocation of EGFP-NES from the nucleus to the cytoplasm was not inhibited by leptomycin B. NES mutations in M1 caused nuclear retention of the protein and increased nuclear accumulation of NEP during transfection. Indeed, as shown by rescued recombinant viruses, mutation of the NES impaired nuclear export of M1 and significantly reduced the virus titer compared to wild-type viruses. The NES-defective M1 was nuclear-retained during infection, accompanied by the lowered efficiency of the nuclear export of vRNPs. In conclusion, M1 nuclear export was specifically dependent on the Flu-A-M1 NES and critical for influenza A virus replication.

PMID:
22345442
[PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/22345442
 
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