These authors contributed equally to this work.
Recruitment of Cellular Clathrin to Viral Factories and Disruption of Clathrin-Dependent Trafficking
Article first published online: 7 JUL 2011
© 2011 John Wiley & Sons A/S
Volume 12, Issue 9, pages 1179–1195, September 2011
How to Cite
Ivanovic, T., Boulant, S., Ehrlich, M., Demidenko, A. A., Arnold, M. M., Kirchhausen, T. and Nibert, M. L. (2011), Recruitment of Cellular Clathrin to Viral Factories and Disruption of Clathrin-Dependent Trafficking. Traffic, 12: 1179–1195. doi: 10.1111/j.1600-0854.2011.01233.x
- Issue published online: 11 AUG 2011
- Article first published online: 7 JUL 2011
- Accepted manuscript online: 10 JUN 2011 08:35AM EST
- Received 20 March 2011, revised and accepted for publication 9 June 2011, uncorrected manuscript published online 10 June 2011, published online 7 July 2011
- membrane trafficking;
- viral factories
The viral factories of mammalian reovirus (MRV) are cytoplasmic structures that serve as sites of viral genome replication and particle assembly. A 721-aa MRV non-structural protein, µNS, forms the factory matrix and recruits other viral proteins to these structures. In this report, we show that µNS contains a conserved C-proximal sequence (711-LIDFS-715) that is similar to known clathrin-box motifs and is required for recruitment of clathrin to viral factories. Clathrin recruitment by µNS occurs independently of infecting MRV particles or other MRV proteins. Ala substitution for a single Leu residue (mutation L711A) within the putative clathrin-binding motif of µNS inhibits clathrin recruitment, but does not prevent formation or expansion of viral factories. Notably, clathrin-dependent cellular functions, including both endocytosis and secretion, are disrupted in cells infected with MRV expressing wild-type, but not L711A, µNS. These results identify µNS as a novel adaptor-like protein that recruits cellular clathrin to viral factories, disrupting normal functions of clathrin in cellular membrane trafficking. To our knowledge, this is the only viral or bacterial protein yet shown to interfere with clathrin functions in this manner. The results additionally establish a new approach for studies of clathrin functions, based on µNS-mediated sequestration.