CD4 and Zika virus infectious disease: DENV 12M animals had also a significantly higher frequency of CD107a+ cells prior to ZIKV infection (P<0.0001; mean diff.: -0.8775, CI95%: -1.25 to -0.503) against the whole DENV antigen (Fig 5A, upper panel, right) while a significant increase in reactivity of CD107a+ CD4+ cells was observed against ZIKV envelope and non-structural antigens on 30 days p.i. (P<0.05; mean diff.: -0.4421, CI95%: -0.8616 to -0.02263 and P<0.05; mean diff.: -0.8775, CI95%: -1.251 to -0.5035, respectively) (Fig 5A, lower panel, right).