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Journal of Virology, January 2006, p. 252-261, Vol. 80, No. 1
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.1.252-261.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Defective Assembly of Influenza A Virus due to a Mutation in the Polymerase Subunit PA

John F. Regan,1 Yuying Liang,2 and Tristram G. Parslow2*

BioMedical Sciences Graduate Program, University of California, San Francisco, California 94143,1 Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 303222

Received 23 June 2005/ Accepted 10 October 2005

The RNA-dependent RNA polymerase of influenza A virus is composed of three subunits that together synthesize all viral mRNAs and also replicate the viral genomic RNA segments (vRNAs) through intermediates known as cRNAs. Here we describe functional characterization of 16 site-directed mutants of one polymerase subunit, termed PA. In accord with earlier studies, these mutants exhibited diverse, mainly quantitative impairments in expressing one or more classes of viral RNA, with associated infectivity defects of varying severity. One PA mutant, however, targeting residues 507 and 508, caused only modest perturbations of RNA expression yet completely eliminated the formation of plaque-forming virus. Polymerases incorporating this mutant, designated J10, proved capable of synthesizing translationally active mRNAs and of replicating diverse cRNA or vRNA templates at levels compatible with viral infectivity. Both the mutant protein and its RNA products were appropriately localized in the cytoplasm, where influenza virus assembly occurs. Nevertheless, J10 failed to generate infectious particles from cells in a plasmid-based influenza virus assembly assay, and hemagglutinating material from the supernatants of such cells contained little or no nuclease-resistant genomic RNA. These findings suggest that PA has a previously unrecognized role in assembly or release of influenza virus virions, perhaps influencing core structure or the packaging of vRNAs or other essential components into nascent influenza virus particles.

* Corresponding author. Mailing address: Department of Pathology and Laboratory Medicine, Emory University, 1364 Clifton Road NE, Room H-184, Atlanta, GA 30322. Phone: (404) 727-8657. Fax: (404) 727-3133. E-mail: tparslo{at}emory.edu.

Journal of Virology, January 2006, p. 252-261, Vol. 80, No. 1
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.1.252-261.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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