The cholesterol recognition/interaction amino acid consensus motif of the influenza A virus M2 protein is not required for virus replication but contributes to virulence.

Virology
Shaun M StewartAndrew Pekosz

Abstract

Influenza A virus particles assemble and bud from plasma membrane domains enriched with the viral glycoproteins but only a small fraction of the total M2 protein is incorporated into virus particles when compared to the other viral glycoproteins. A membrane proximal cholesterol recognition/interaction amino acid consensus (CRAC) motif was previously identified in M2 and suggested to play a role in protein function. We investigated the importance of the CRAC motif on virus replication by generating recombinant proteins and viruses containing amino acid substitutions in this motif. Alteration or completion of the M2 CRAC motif in two different virus strains caused no changes in virus replication in vitro. Viruses lacking an M2 CRAC motif had decreased morbidity and mortality in the mouse model of infection, suggesting that this motif is a virulence determinant which may facilitate virus replication in vivo but is not required for basic virus replication in tissue culture.

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Citations

Jun 15, 2011·Viruses·Mark Yondola, Carol Carter
Feb 9, 2012·Advances in Virology·Michael Veit, Bastian Thaa
May 3, 2012·Biology of the Cell·Michael Veit
Mar 31, 2016·Biophysical Journal·E Vindana EkanayakeTimothy A Cross
Jan 30, 2013·Biochemical Society Transactions·Michael VeitLarisa V Kordyukova
Jan 18, 2011·Virology·Jeremy S Rossman, Robert A Lamb
Feb 17, 2017·Journal of Virology·George P Leser, Robert A Lamb
Aug 29, 2018·Proceedings of the National Academy of Sciences of the United States of America·Jesper J MadsenGregory A Voth
Jul 18, 2018·Biology of Sex Differences·Meghan S VermillionSabra L Klein
Nov 22, 2017·Proceedings of the National Academy of Sciences of the United States of America·Matthew R ElkinsMei Hong
Aug 31, 2018·Journal of Virology·Nicholas WohlgemuthAndrew Pekosz
Jul 10, 2020·The Journal of Physical Chemistry. B·Agnieszka MartynaJeremy S Rossman

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