NDLI: New regulatory mechanisms for the intracellular localization and trafficking of influenza A virus NS1 protein revealed by comparative analysis of A/PR/8/34 and A/Sydney/5/97.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Han, Han Cui, Zong-Qiang Wang, Wei Zhang, Zhi-Ping Wei, Hong-Ping Zhou, Ya-Feng Zhang, Xian-En
Description	Author Affiliation: Han H ( State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences Wuhan 430071, PR China.)
Abstract	During influenza A virus infection, the NS1 protein is engaged in different functions in different intracellular compartments. In this study, we showed that the NS1 of A/PR/8/34 localized in different positions from that of A/Sydney/5/97 when transiently expressed in Madin-Darby canine kidney cells. Residue 221 of NS1 was identified to be a new key residue involved in the C-terminal nuclear localization signal (NLS) and nucleolar localization signal (NoLS) of NS1 from A/Sydney/5/97. Analysis of chimeric NS1 and further mutants showed that residues responsible for the binding between NS1 and the cleavage and polyadenylation specificity factor (CPSF) are correlated with the intracellular localization of transiently expressed NS1 proteins. Fluorescence loss in photobleaching imaging revealed that the NS1 protein with both functional NLSs and nuclear export signal (NES) was able to shuttle between the nucleus and cytoplasm. Drug inhibition experiments and fluorescence resonance energy transfer analysis suggested that NS1 was exported out of the cell nuclei via a Crm1-independent pathway. Moreover, it is likely that another cytoplasmic localization-related sequence exists in the NS1 protein other than the leucine-rich NES. These findings provide new insights into the mechanism of intracellular localization and trafficking of influenza A virus NS1 protein, which is important for understanding its function.
File Format	HTM / HTML
ISSN	00221317
Issue Number	Pt 12
Volume Number	91
e-ISSN	14652099
Journal	Journal of General Virology
Language	English
Publisher	Microbiology Society
Publisher Date	2010-12-01
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Cell Nucleolus Cell Line Research Support, Non-u.s. Gov't Viral Nonstructural Proteins Discipline Virology Metabolism Karyopherins Protein Sorting Signals Journal Article Protein Transport Mutant Proteins Influenza A Virus Chemistry Animals Recombination, Genetic Dogs Genetics Physiology Receptors, Cytoplasmic And Nuclear Cell Nucleus Cytoplasm
Content Type	Text
Resource Type	Article
Subject	Virology

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