An Epidemic Zika Virus Isolate Drives Enhanced T Follicular Helper Cell and B Cell-Mediated Immunity

Zika virus (ZIKV) is a mosquito-borne pathogen that recently caused a series of increasingly severe outbreaks. We previously demonstrated that, compared with a pre-epidemic isolate (ZIKV^CDN), a Brazilian ZIKV isolate (ZIKV^BR) possesses a novel capacity to suppress host immunity, resulting in delayed viral clearance. However, whether ZIKV^BR modulates CD4 T cell responses remains unknown. In this study, we show that, in comparison with ZIKV^CDN infection, CD4 T cells are less polarized to the Th1 subtype following ZIKV^BR challenge in mice. In contrast, we observed an enhanced accumulation of T follicular helper cells 10, 14, and 21 d postinfection with ZIKV^BR This response correlated with an enhanced germinal center B cell response and robust production of higher avidity-neutralizing Abs following ZIKV^BR infection. Taken together, our data suggest that contemporary ZIKV strains have evolved to differentially induce CD4 T cell, B cell, and Ab responses and this could provide a model to further define the signals required for T follicular helper cell development.