Viperin is required for optimal Th2 responses and T-cell receptor-mediated activation of NF-κB and AP-1

Abstract

Viperin (virus inhibitory protein, endoplasmic reticulum [ER]-associated, interferon - inducible) has been identified as a highly inducible ER protein that has antiviral activity. Here, we characterized the pheno - type of mice deficient in viperin and examined the biological function of viperin in peripheral T-cell activation and differentiation. Splenic CD4+ T cells deficient in viperin exhibited normal anti-T-cell receptor (TCR)-induced proliferation and IL-2 production, but produced significantly less T helper 2 (Th2) cytokines, including IL-4, IL-5, and IL-13, in association with impaired GATA3 activation, after stimulation with anti-CD3 antibody, which was not restored upon costimulation with anti - CD28. Th2 differentiation of viperin - deficient naive T cells was also impaired in the presence of strong TCR signaling and minimum IL-4, but not under optimal Th2-skewed conditions. In parallel, viperin-deficient T cells showed decreases in NF-κ-B1/p50 and AP-1/JunB DNA binding activities after TCR engagement. Thus, viperin facilitates TCR - mediated GATA-3 activation and optimal Th2 cytokine production by modulating NF-κB and AP-1 activities. κ 2009 by The American Society of Hematology.