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The arginine residues at positions 76-78 of influenza A virus matrix protein M1 play an important role in viral replication

tetano

Editor, Senior Moderator
J Virol. 2011 Nov 16. [Epub ahead of print]
The arginine residues at positions 76-78 of influenza A virus matrix protein M1 play an important role in viral replication.
Das SC, Watanabe S, Hatta M, Noda T, Neumann G, Ozawa M, Kawaoka Y.
Source

Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA.
Abstract

Influenza A virus matrix protein (M1) plays an important role in virus assembly and budding. Besides a well-characterized basic amino acid rich nuclear localization signal region at positions 101-105, M1 contains another basic amino acid stretch at positions 76-78 that is highly conserved among influenza A and B viruses, suggesting the importance of this stretch. To understand the role of these residues in virus replication, we mutated them to either lysine (K), alanine (A), or aspartic acid (D). We could generate viruses possessing either single or combination substitutions with K or single substitution with A at any of these positions, but not those with double substitutions with A or a single substitution with D. Viruses with the single substitution with A exhibited slower growth and had lower nucleoprotein/M1 quantitative ratio in virions compared to the wild-type virus. In cells infected with a virus possessing the single substitution with A at position 77 or 78 (R77A or R78A, respectively), the mutated M1 localized in patches at the cell periphery where nucleoprotein and hemagglutinin co-localized. Transmission electron microscopy showed that virus possessing M1 R77A or R78A, but not the wild-type virus, was present in vesicular structures, indicating a defect in virus assembly and/or budding. The M1 mutations that did not support virus generation exhibited an aberrant M1 intracellular localization and affected protein incorporation into virus-like particles. These results indicate that the basic amino acid stretch of M1 plays a critical role in influenza virus replication.

PMID:
22090133
[PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/22090133
 
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