Recruitment of cellular clathrin to viral factories and disruption of clathrin-dependent trafficking

Tijana Ivanovic, Steeve Boulant, Marcelo Ehrlich, Aleksander A. Demidenko, Michelle M. Arnold, Tomas Kirchhausen*, Max L. Nibert

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1179-1195
Number of pages17
JournalTraffic
Volume12
Issue number9
DOIs
StatePublished - Sep 2011

Funding

FundersFunder number
National Institute of Allergy and Infectious DiseasesR56AI067445

    Keywords

    • Adaptor
    • Clathrin
    • Membrane trafficking
    • Reovirus
    • Viral factories

    Fingerprint

    Dive into the research topics of 'Recruitment of cellular clathrin to viral factories and disruption of clathrin-dependent trafficking'. Together they form a unique fingerprint.

    Cite this