Zika Virus: What Have We Learnt Since the Start of the Recent Epidemic?

Abstract

Zika is a viral disease transmitted mainly by mosquitoes of the genus Aedes. In recent years, it has expanded geographically, changing from an endemic mosquito-borne disease across equatorial Asia and Africa, to an epidemic disease causing large outbreaks in several areas of the world. With the recent Zika virus (ZIKV) outbreaks in the Americas, the disease has become a focus of attention of public health agencies and of the international research community, especially due to an association with neurological disorders in adults and to the severe neurological and ophthalmological abnormalities found in fetuses and newborns of mothers exposed to ZIKV during pregnancy. A large number of studies have been published in the last 3 years, revealing the structure of the virus, how it is transmitted and how it affects human cells. Many different animal models have been developed, which recapitulate several features of ZIKV disease and its neurological consequences. Moreover, several vaccine candidates are now in active preclinical development, and three of them have already entered phase I clinical trials. Likewise, many different compounds targeting viral and cellular components are being tested in in vitro and in experimental animal models. This review aims to discuss the current state of this rapidly growing literature from a multidisciplinary perspective, as well as to present an overview of the public health response to Zika and of the perspectives for the prevention and treatment of this disease.

Keywords: Guillain–Barré syndrome; antivirals; epidemiology; flavivirus; microcephaly.

FIGURE 1

Classification of countries and territories regarding vector-borne Zika virus transmission. Map of the current Zika virus transmission based on the European Center for Disease Prevention and Control (ECDC) adaptation of the World Health Organization (WHO)’s Zika virus country classification scheme (https://ecdc.europa.eu/en/publications-data/current-zika-virus-transmission-list-countries-ecdc-adaptation-whos-zika-virus - accessed 16 July 2017). The map was generated using GADM database of Global Administrative Areas shapefiles (http://www.gadm.org/) and Openlayers plugin within QGIS 2.18.9 (Development Team, 2017, available at http://www.qgis.org/en/site).

FIGURE 2

Phylogram of Zika virus (ZIKV). The phylogenetic tree was based on the sequence of NS5. Multiple alignment was performed using MUSCLE (Edgar, 2004) and the tree was constructed by the Maximum Likelihood method using PhyML (Guindon et al., 2010) and Phylogeny.fr (Dereeper et al., 2008). Spondweni virus was included as the outgroup control.

FIGURE 3

Genomic organization, virion structure, and organization of the E glycoprotein of Zika virus (ZIKV). (A) Schematic view of the genomic organization of ZIKV. The single open reading frame (ORF; boxes) that encodes both structural (C-prM/M and E) and non-structural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) is flanked by two untranslated regions (UTRs). Notice the presence of a 5′ cap and the lack of a poly(A) tail at the 3′ end of the genome. (B) Surface representation of a ZIKV mature particle. The E monomers are colored in blue, orange and green to facilitate the interpretation of their distribution. Image was produced using the cryo-electron microscopy data available (Protein Data Bank entry 5IRE). (C) Structure of a monomer of the soluble ectodomain of E glycoprotein of ZIKV. The ribbon diagram was based on the atomic coordinates solved by X-ray crystallography (Protein Data Bank entry 5JHM). DI in red, DII in yellow, and DIII in blue. Fusion loop is highlighted in green.

FIGURE 4

Clinical manifestations and consequences of Zika virus (ZIKV) infection. Schematic illustration of the effects described in adults and fetuses/newborns after ZIKV infection. Figure created in the Mind the Graph platform.

FIGURE 5

Mechanisms of Zika virus (ZIKV)-induced neural damage. Schematic illustration of the main findings from in vitro and in vivo models of Zika virus infection. Figure created in the Mind the Graph platform. NPCs: neural progenitor cells; NSCs: neural stem cells.