Evolution of the innate and adaptive immune response in women with acute Zika virus infection

Zika virus (ZIKV) is a flavivirus that is closely related to other human pathogens, such as dengue virus (DENV)¹. Primary transmission usually involves Aedes aegypti, which has expanded its distribution range considerably², although rarer infection routes, including mother-to-fetus transmission, sexual contact and blood transfusion, have also been observed^3-7. Primary ZIKV infection is usually asymptomatic or mild in adults, with quickly resolved blood viraemia, but ZIKV might persist for months in saliva, urine, semen, breast milk and the central nervous system^8-12. During a recent ZIKV outbreak in South America, substantial numbers of neurological complications, such as Guillain-Barré syndrome, were reported^13,14 together with cases of microcephaly and associated developmental problems in infants born to women infected with ZIKV during pregnancy^15-20, highlighting the clinical importance of this infection. Analyses of the human immune response to ZIKV are lacking^21-28, but the recent outbreak has provided an opportunity to assess ZIKV immunity using current immunological methods. Here, we comprehensively assess the acute innate and adaptive immune response to ZIKV infection in ten women who were recruited during early infection and followed through reconvalescence. We define a cascade of events that lead to immunological control of ZIKV, with previous exposure to DENV impacting some, but not all, mediators of antiviral immunity.