Along with other viruses in this family, Zika virus is enveloped and icosahedral with a nonsegmented, 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.

The virus was first isolated in 1947 from a rhesus macaque in the Zika Forest of Uganda and in 1968 was isolated for the first time from humans in Nigeria. From 1951 through 1981, evidence of human infection was reported from other African countries such as the Central African Republic, Egypt, Gabon, Sierra Leone, Tanzania, and Uganda, as well as in parts of Asia including India, Indonesia, Malaysia, the Philippines, Thailand, and Vietnam.

The pathogenesis of the virus is hypothesized to start with an infection of dendritic cells near the site of inoculation, followed by a spread to lymph nodes and the bloodstream. Flaviviruses generally replicate in the cytoplasm, but Zika virus antigens have been found in infected cell nuclei.

There are two lineages of Zika virus, the African lineage and the Asian lineage. Phylogenetic studies indicate that the virus spreading in the Americas is most closely related to French Polynesian strains. Complete genome sequences of Zika viruses have been published.[18] Recent preliminary findings from sequences in the public domain uncovered a possible change in nonstructural protein 1 codon usage that may increase the viral replication rate in humans.