RT Journal Article
SR Electronic
T1 Determination of dsRNA interactome upon Sindbis virus infection in human cells identifies SFPQ as a critical proviral factor
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.09.434591
DO 10.1101/2021.03.09.434591
A1 Erika Girardi
A1 Mélanie Messmer
A1 Paula Lopez
A1 Aurélie Fender
A1 Johana Chicher
A1 Béatrice Chane-Woon-Ming
A1 Philippe Hammann
A1 Sébastien Pfeffer
YR 2021
UL http://biorxiv.org/content/early/2021/03/09/2021.03.09.434591.abstract
AB Viruses are obligate intracellular parasites, which depend on the host cellular machineries to replicate their genome and complete their infectious cycle. Long double stranded (ds)RNA is a common viral by-product originating during RNA virus replication and is universally sensed as a danger signal to trigger the antiviral response. As a result, viruses hide dsRNA intermediates into viral replication factories and have evolved strategies to hijack cellular proteins for their benefit. The characterization of the host factors associated to viral dsRNA and involved in viral replication remains a major challenge to develop new antiviral drugs against RNA viruses. Here, we performed anti-dsRNA immunoprecipitation followed by mass spectrometry to fully characterize the dsRNA interactome in Sindbis virus (SINV) infected human HCT116 cells. Among the validated factors, we characterized SFPQ (Splicing factor, proline-glutamine rich) as a new dsRNA-associated factor upon SINV infection. We proved that SFPQ is able to directly bind to dsRNAs in vitro, that its association to dsRNA is independent of single-stranded (ss)RNA flanking regions in vivo and that it is able to bind to the viral genome upon infection. Furthermore, we showed that both knock-down and knock-out of SFPQ reduce SINV infection in human HCT116 and SK-N-BE(2) cells, suggesting that SFPQ could enhance viral replication. Overall, this study not only represents a resource to further study SINV dsRNA-associated factors upon infection but also identifies SFPQ as a new proviral dsRNA binding protein.Competing Interest StatementThe authors have declared no competing interest.