Article révisé par les pairs
Résumé : Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that has been responsible for an epidemic outbreak of unprecedented magnitude in recent years. Since then, significant efforts have been made to better understand the biology of this virus but we still have a poor knowledge of CHIKV interactions with host cell components at the molecular level. Here we describe the extensive use of high-throughput yeast two-hybrid (HT-Y2H) to characterize interactions between CHIKV and human proteins. A total of 22 high-confidence interactions, which essentially involved the viral non-structural protein nsP2, were identified and further validated by protein complementation assay (PCA). These results were integrated to a larger network obtained by extensive mining of literature for alphavirus-host interactions. To investigate the role of cellular proteins interacting with nsP2, gene silencing experiments were performed in cells infected by a recombinant CHIKV expressing Renilla luciferase as a reporter. Collected data involve heterogeneous nuclear ribonucleoprotein K (hnRNP-K) and ubiquilin 4 (UBQLN4) in CHIKV replication in vitro. In addition, we showed that CHIKV nsP2 induces a cellular shut-off as previously reported for other Old-World alphaviruses, and determined that among binding partners identified by yeast two-hybrid, the tetratricopeptide repeat protein 7B (TTC7B) plays a significant role in this activity. Altogether, this report provides a first interaction map between CHIKV and human proteins, and involves new host cell proteins in the replication cycle of this virus.

Documents en relation

DI-fusion