The findings presented here show that activation of TLR8 is induced by EBV/lytic genes in HD and SSc EBV-p2089-infected monocytes and that expression of TLR8 and IFN innate immune mediators is significantly increased in freshly isolated dcSSc monocytes carrying infectious EBV compared to monocytes from HDs. Here, IFNA1 is linked to systemic sclerosis.