New host factors important for respiratory syncytial virus (RSV) replication revealed by a novel microfluidics screen for interactors of matrix (M) protein

Sarit Kipper, Samar Hamad, Leon Caly, Dorit Avrahami, Eran Bacharach, David A Jans, Doron Gerber, Monika Bajorek

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23 Citations (Scopus)

Abstract

Although human respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and pneumonia in infants and elderly worldwide, there is no licensed RSV vaccine or effective drug treatment available. The RSV Matrix (M) protein plays key roles in virus life cycle, being found in the nucleus early in infection in a transcriptional inhibitory role, and later localizing in viral inclusion bodies (IBs) before coordinating viral assembly and budding at the plasma membrane. In this study we used a novel, high throughput microfluidics platform and custom human ORF library to identify novel host cell binding partners of RSV M. Novel interactors identified included proteins involved in host transcription regulation, the innate immunity response, cytoskeletal regulation, membrane remodelling and cellular trafficking. A number of these interactions were confirmed by immunoprecipitation and cellular colocalization approaches. Importantly, the physiological significance of M interaction with the actin-binding protein cofilin 1, caveolae protein Caveolin 2 and the zinc finger protein ZNF502 was confirmed. siRNA knockdown of the host protein levels resulted in reduced RSV virus production in infected cells. These results have important implications for future antiviral strategies aimed at targets of RSV M in the host cell.
Original languageEnglish
Pages (from-to)532 - 543
Number of pages12
JournalMolecular & Cellular Proteomics
Volume14
Issue number3
DOIs
Publication statusPublished - 2015

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