Zika fever is caused by the Zika virus (ZIKV), an arthropod-borne virus (arbovirus). The Zika virus is a member of the Flavivirus genus in the family Flaviviridae. It is related to dengue, yellow fever, West Nile and Japanese encephalitis, viruses that are also members of the virus family Flaviviridae.

Video 1. What is Zika? WHO information video. Epidemiologist Erika Garcia provides more information about Zika virus disease.

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Along with other viruses in the Flaviviridae family, Zika virus is enveloped and icosahedral with a non-segmented, single-stranded, positive sense RNA genome. It is most closely related to the Spondweni virus and is one of the two viruses in the Spondweni virus clade. Virus particles are 40 nm in diameter, with an outer envelope and a dense inner core. The Zika virus RNA is 10,617-nucleotide long. The Zika virus genome encodes for a polyprotein with three structural proteins, capsid, premembrane/membrane, and envelope (including the envelope-154 glycosylation motif previously associated with virulence), and seven nonstructural proteins, NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5 encodes for (see figure 1). The positive-sense RNA genome can be directly translated into viral proteins. The site of mRNA transcription is in the cell cytoplasm. One of the structural proteins encapsulates the virus. This protein is the flavivirus envelope glycoprotein, that binds to the endosomal membrane of the host cell to initiate endocytosis. The RNA genome forms a nucleocapsid along with copies of the 12-kDa capsid protein. The nucleocapsid, in turn, is enveloped within a host-derived membrane modified with two viral glycoproteins. Viral genome replication depends on the making of double-stranded RNA from the single-stranded, positive-sense RNA (ssRNA(+)) genome followed by transcription and replication to provide viral mRNAs and new ssRNA(+) genomes.

A longitudinal study shows that 6 hours after cells are infected with Zika virus, the vacuoles and mitochondria in the cells begin to swell. This swelling becomes so severe, it results in cell death, also known as paraptosis. This form of programmed cell death requires gene expression. IFITM3 is a trans-membrane protein in a cell that is able to protect it from viral infection by blocking virus attachment. Cells are most susceptible to Zika infection when levels of IFITM3 are low. Once the cell has been infected, the virus restructures the endoplasmic reticulum, forming the large vacuoles, resulting in cell death.

Figure 1. Zika virus genome structure