Viperin restricts chikungunya virus replication and pathology

J Clin Invest. 2012 Dec;122(12):4447-60. doi: 10.1172/JCI63120. Epub 2012 Nov 19.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alphavirus Infections / immunology*
  • Alphavirus Infections / pathology
  • Alphavirus Infections / virology
  • Animals
  • Case-Control Studies
  • Chikungunya virus / immunology
  • Chikungunya virus / physiology*
  • Cluster Analysis
  • Endoplasmic Reticulum / metabolism
  • Female
  • Foot / pathology
  • Foot / virology
  • Gene Expression Regulation / immunology
  • HEK293 Cells
  • Host-Pathogen Interactions
  • Humans
  • Immunity, Innate / genetics
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / metabolism
  • Monocytes / virology
  • Oxidoreductases Acting on CH-CH Group Donors
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Protein Transport
  • Proteins / genetics
  • Proteins / metabolism
  • Proteins / physiology*
  • Statistics, Nonparametric
  • Transcriptome
  • Virus Replication*


  • Proteins
  • Oxidoreductases Acting on CH-CH Group Donors
  • RSAD2 protein, human