title: Viperin restricts chikungunya virus replication and pathology.
abstract: Chikungunya virus (CHIKV) is a mosquito-borne arthralgia arbovirus that is reemergent in sub-Saharan Africa and Southeast Asia. CHIKV infection has been shown to be self-limiting, but the molecular mechanisms of the innate immune response that control CHIKV replication remain undefined. Here, longitudinal transcriptional analyses of PBMCs from a cohort of CHIKV-infected patients revealed that type I IFNs controlled CHIKV infection via RSAD2 (which encodes viperin), an enigmatic multifunctional IFN-stimulated gene (ISG). Viperin was highly induced in monocytes, the major target cell of CHIKV in blood. Anti-CHIKV functions of viperin were dependent on its localization in the ER, and the N-terminal amphipathic α-helical domain was crucial for its antiviral activity in controlling CHIKV replication. Furthermore, mice lacking Rsad2 had higher viremia and severe joint inflammation compared with wild-type mice. Our data demonstrate that viperin is a critical antiviral host protein that controls CHIKV infection and provide a preclinical basis for the design of effective control strategies against CHIKV and other reemerging arthrogenic alphaviruses.
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.
authors.forename: Terk-Shin
authors.initials: TS
authors.lastname: Teng
authors.forename: Suan-Sin
authors.initials: SS
authors.lastname: Foo
authors.forename: Diane
authors.initials: D
authors.lastname: Simamarta
authors.forename: Fok-Moon
authors.initials: FM
authors.lastname: Lum
authors.forename: Teck-Hui
authors.initials: TH
authors.lastname: Teo
authors.forename: Aleksei
authors.initials: A
authors.lastname: Lulla
authors.forename: Nicholas K W
authors.initials: NK
authors.lastname: Yeo
authors.forename: Esther G L
authors.initials: EG
authors.lastname: Koh
authors.forename: Angela
authors.initials: A
authors.lastname: Chow
authors.forename: Yee-Sin
authors.initials: YS
authors.lastname: Leo
authors.forename: Andres
authors.initials: A
authors.lastname: Merits
authors.forename: Keh-Chuang
authors.initials: KC
authors.lastname: Chin
authors.forename: Lisa F P
authors.initials: LF
authors.lastname: Ng
mesh_terms: D018354:Alphavirus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D000818:Animals; D016022:Case-Control Studies; D002646:Chikungunya virus / Q000276:immunology / Q000502:physiology*; D016000:Cluster Analysis; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D005528:Foot / Q000473:pathology / Q000821:virology; D005786:Gene Expression Regulation / Q000276:immunology; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism / Q000821:virology; D044925:Oxidoreductases Acting on CH-CH Group Donors; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018709:Statistics, Nonparametric; D059467:Transcriptome; D014779:Virus Replication; D000090123:Viperin Protein
chemical_list: D044925:Oxidoreductases Acting on CH-CH Group Donors; D011506:Proteins; C444427:RSAD2 protein, human; D000090123:Viperin Protein