Zika in the Americas, year 2: What have we learned? What gaps remain? A report from the Global Virus Network

Abstract

In response to the outbreak of Zika virus (ZIKV) infection in the Western Hemisphere and the recognition of a causal association with fetal malformations, the Global Virus Network (GVN) assembled an international taskforce of virologists to promote basic research, recommend public health measures and encourage the rapid development of vaccines, antiviral therapies and new diagnostic tests. In this article, taskforce members and other experts review what has been learned about ZIKV-induced disease in humans, its modes of transmission and the cause and nature of associated congenital manifestations. After describing the make-up of the taskforce, we summarize the emergence of ZIKV in the Americas, Africa and Asia, its spread by mosquitoes, and current control measures. We then review the spectrum of primary ZIKV-induced disease in adults and children, sites of persistent infection and sexual transmission, then examine what has been learned about maternal-fetal transmission and the congenital Zika syndrome, including knowledge obtained from studies in laboratory animals. Subsequent sections focus on vaccine development, antiviral therapeutics and new diagnostic tests. After reviewing current understanding of the mechanisms of emergence of Zika virus, we consider the likely future of the pandemic.

Keywords: Antiviral therapy; Arbovirus; Congenital manifestations; Maternal-fetal transmission; Vaccines; Zika virus.

Fig. 1

Sylvatic and urban cycling of Zika virus and its mosquito vectors.

Fig. 2

Characteristics of ideal anti-Zika drugs (see text).

Fig. 3

Chemical structures of reported ZIKV inhibitors. A) FDA-approved drugs or B) Novel antiviral agents.

Fig. 4

Z-Quick Test overview (Magnani et al., 2017). Ninety-six-well ELISA plates are coated with an anti-flavivirus mAb overnight. The next day, plates are washed with PBS-T and block with 5% non-fat milk for 1 h at 37 °C. The plates are then washed, ZIKV is added to each well, and the plates are incubated at room temperature for 1 h. Plates are washed again, patient plasma is added to wells, and the plates are incubated for 1 h at 37 °C. The plates are then washed, the P1F12 ZIKV-specific antibody is added, and incubated for 1 h at 37 °C. During this step, if the patient was exposed to ZIKV, the antibodies in the patient’s plasma should block the binding of the P1F12 mAb. Next, the plates are washed, a HRP detection antibody is added, and the plates are incubated at 37 °C for 1 h. Lastly, the wells are washed, TMB is used to develop the HRP, and the wells are read using a spectrophotometer.