<i>Viperin</i> controls chikungunya virus–specific pathogenic T cell IFNγ Th1 stimulation in mice

Abstract

Chikungunya virus (CHIKV) has been a worldwide threat since its reemergence in La Reunion Island in 2004. Expression of the interferon-stimulated protein <i>Viperin</i> correlates with viral load burden in patients, and studies in mice have demonstrated its role to limit disease severity against CHIKV infection. Using <i>Viperin</i> ^<i>-/-</i> mice, we aimed to understand the contribution of <i>Viperin</i> to the T-cell immune response against CHIKV. CD4 T-cell depletion in <i>Viperin</i> ^<i>-/-</i> mice showed that increased late acute joint inflammation (5-8 d postinfection) was exclusively mediated by T cells. Specifically, CHIKV-infected <i>Viperin</i> ^<i>-/-</i> mice showed an increased INFγ Th1 profile of CD4 T cells, enhanced INFγ stimulation by APCs, an increased INFγ secretion profile in the joint microenvironment, and increased numbers of inflammatory monocytes in virus-infected joints compared with WT mice. Bone marrow grafting experiments showed that <i>Viperin</i> expression in both hematopoietic and non-hematopoietic cells is instrumental in reducing disease severity associated with a CD4 T-cell response.