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Identification of the domains of the influenza A virus M1 matrix protein required for NP binding, oligomerization and incorporation into virions

Dawn Fisher

Anne E. Mullin

Debra Elton

Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK

Correspondence
Paul Digard
pd1{at}mole.bio.cam.ac.uk

The matrix (M1) protein of influenza A virus is a multifunctional protein that plays essential structural and functional roles in the virus life cycle. It drives virus budding and is the major protein component of the virion, where it forms an intermediate layer between the viral envelope and integral membrane proteins and the genomic ribonucleoproteins (RNPs). It also helps to control the intracellular trafficking of RNPs. These roles are mediated primarily via protein–protein interactions with viral and possibly cellular proteins. Here, the regions of M1 involved in binding the viral RNPs and in mediating homo-oligomerization are identified. In vitro, by using recombinant proteins, it was found that the middle domain of M1 was responsible for binding NP and that this interaction did not require RNA. Similarly, only M1 polypeptides containing the middle domain were able to bind to RNP–M1 complexes isolated from purified virus. When M1 self-association was examined, all three domains of the protein participated in homo-oligomerization although, again, the middle domain was dominant and self-associated efficiently in the absence of the N- and C-terminal domains. However, when the individual fragments of M1 were tagged with green fluorescent protein and expressed in virus-infected cells, microscopy of filamentous particles showed that only full-length M1 was incorporated into budding virions. It is concluded that the middle domain of M1 is primarily responsible for binding NP and self-association, but that additional interactions are required for efficient incorporation of M1 into virus particles.

Present address: Stem Cell Sciences plc, Roger Land Building, King's Buildings, West Mains Road, Edinburgh, EH9 3JK, UK.

Present address: British Columbia Research Institute, 950 West 28th Avenue, Rm 318, Vancouver BC, V5Z 4H4, Canada.

Present address: Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk, CB8 7UU, UK.

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