![Sample our Health and Social Care journals, sign in here to start your FREE access for 14 days]({"type":"image" , "src" : "/sda/5938/TOC-Subject-Sample-2021-Health-Social-Care.jpg"})
Abstract
Chikungunya virus (CHIKV) is a re-emerging alphavirus which causes severe and prolonged arthralgic febrile illness. The recent global spread of the virus and lack of approved therapeutic options makes it imperative to gain greater insight into the molecular mechanisms underlying CHIKV pathogenesis, in particular host factors recruited by the virus. In the current study, we identify sphingosine kinase 2 (SK2) as a CHIKV host factor co-localized with the viral replication complex (VRC) during infection. SK2 was demonstrated to co-localize with viral RNA and nonstructural proteins. Targeted impairment of SK2 expression or function significantly inhibited CHIKV infection. Furthermore, affinity purification-mass spectrometry studies revealed that SK2 associates with a number of proteins involved in cellular gene expression specifically during viral infection, suggesting a role in replication. Collectively these results identify SK2 as a novel CHIKV host factor.
We thank the Dr Marc Lecuit (Institut Pasteur, Paris, France), Dr Subhash G Vasudevan (Duke-NUS Graduate Medical School, Singapore), Dr Charles D Smith (MUSC, Charleston, SC, USA), and Dr Michael Farzan (The Scripps Research Institute, Jupiter, FL, USA) for providing the nsP2 antibody, GFP-nsP/capsid plasmids, ABC294640 and MLV-GFP pseudotype plasmids respectively. We also thank Julie Tran and Dr Veronica Soloveva (USAMRIID, Frederick, MD, USA) for technical assistance and Dr Steven Bradfute (UNM, Albuquerque, NM, USA) for critical review of this manuscript. These studies were in part supported by Defense Threat Reduction Agency, Joint Science and Technology Office. The opinions, interpretations, conclusions, and recommendation in this report are not necessarily endorsed by the US Army.
