title: Sphingosine kinase 2 is a chikungunya virus host factor co-localized with the viral replication complex.
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.
authors.affiliation: Molecular and Translational Science, US Army Medical Research Institute of Infectious Diseases (USAMRIID) , Frederick, MD 21702-5011, USA.
authors.forename: St Patrick
authors.initials: SP
authors.lastname: Reid
authors.affiliation: Molecular and Translational Science, US Army Medical Research Institute of Infectious Diseases (USAMRIID) , Frederick, MD 21702-5011, USA.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Tritsch
authors.affiliation: Molecular and Translational Science, US Army Medical Research Institute of Infectious Diseases (USAMRIID) , Frederick, MD 21702-5011, USA ; Perkin Elmer , Waltham, MA 02451, USA.
authors.forename: Krishna
authors.initials: K
authors.lastname: Kota
authors.affiliation: Molecular and Translational Science, US Army Medical Research Institute of Infectious Diseases (USAMRIID) , Frederick, MD 21702-5011, USA.
authors.forename: Chih-Yuan
authors.initials: CY
authors.lastname: Chiang
authors.affiliation: Molecular and Translational Science, US Army Medical Research Institute of Infectious Diseases (USAMRIID) , Frederick, MD 21702-5011, USA.
authors.forename: Lian
authors.initials: L
authors.lastname: Dong
authors.affiliation: Molecular and Translational Science, US Army Medical Research Institute of Infectious Diseases (USAMRIID) , Frederick, MD 21702-5011, USA.
authors.forename: Tara
authors.initials: T
authors.lastname: Kenny
authors.affiliation: Molecular and Translational Science, US Army Medical Research Institute of Infectious Diseases (USAMRIID) , Frederick, MD 21702-5011, USA.
authors.forename: Ernest E
authors.initials: EE
authors.lastname: Brueggemann
authors.affiliation: Molecular and Translational Science, US Army Medical Research Institute of Infectious Diseases (USAMRIID) , Frederick, MD 21702-5011, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Ward
authors.affiliation: Molecular and Translational Science, US Army Medical Research Institute of Infectious Diseases (USAMRIID) , Frederick, MD 21702-5011, USA.
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Cazares
authors.affiliation: Molecular and Translational Science, US Army Medical Research Institute of Infectious Diseases (USAMRIID) , Frederick, MD 21702-5011, USA.
authors.forename: Sina
authors.initials: S
authors.lastname: Bavari
mesh_terms: D018354:Alphavirus Infections / Q000517:prevention & control / Q000821:virology*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D002646:Chikungunya virus / Q000201:enzymology* / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D015967:Gene Expression Regulation, Viral; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D018482:Muscle, Skeletal / Q000166:cytology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012367:RNA, Viral / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology; D000099157:Sphingosine Kinase
chemical_list: D017853:Phosphotransferases (Alcohol Group Acceptor); D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; D000099157:Sphingosine Kinase
keywords: chikungunya virus; nsP3; sphingosine kinase 2; viral replication complex