In the present study, we show that infection of 4-week-old type 1 IFNR-deficient mice with the ZIKV Brazilian strain, PE243, triggered an early and robust adaptive immune response, including the activation of a high percentage of CD4+ T cells capable of producing IFNγ, increasing GC-B cells and anti-ZIKV neutralizing antibody titers, associated with reduction in viral titles in the CNS and survival. This evidence concerns the gene CD4 and infection.