Zika virus is an enveloped, positive-sense, single-stranded RNA virus belonging to the genus Flavivirus within the family Flaviviridae. It is closely related to other medically important flaviviruses such as dengue, yellow fever, West Nile, and Japanese encephalitis viruses. Two main lineages of Zika virus are recognised, the African lineage and the Asian lineage, with the Asian lineage responsible for the large outbreaks and epidemics observed over the past decade.

Zika virus enters host cells through receptor-mediated endocytosis, using a range of candidate attachment factors and receptors depending on the cell type, including AXL, DC-SIGN, and TIM/TAM family proteins. Following entry, the acidic environment of the endosome triggers fusion of the viral envelope with the endosomal membrane, releasing the viral genome into the cytoplasm. The positive-sense RNA genome is translated directly into a single polyprotein, which is cleaved by viral and host proteases into three structural proteins and seven non-structural proteins. Replication takes place on rearranged endoplasmic reticulum membranes, and progeny virions assemble and mature as they traffic through the secretory pathway before release from the cell.

The Zika virus genome encodes structural proteins, capsid, precursor membrane, and envelope, together with non-structural proteins including NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5, which are involved in genome replication, polyprotein processing, and evasion of host innate immune responses. The envelope protein mediates attachment and membrane fusion and is the principal target of neutralising antibodies, while NS1 is secreted from infected cells and is widely used as a diagnostic marker of active infection. Unlike influenza, Zika virus has a non-segmented genome, so genetic diversification occurs primarily through the gradual accumulation of point mutations rather than through reassortment.

Zika virus is transmitted primarily through the bite of infected Aedes mosquitoes, principally Aedes aegypti and Aedes albopictus, which also transmit dengue and chikungunya viruses. Beyond mosquito-borne transmission, Zika virus is unusual among flaviviruses in that it can also be transmitted sexually, from mother to fetus during pregnancy, and, rarely, through blood transfusion. Most infections are asymptomatic or cause mild, self-limiting illness characterised by low-grade fever, maculopapular rash, conjunctivitis, arthralgia, and myalgia. However, infection during pregnancy can cause congenital Zika syndrome, including microcephaly and other severe brain abnormalities in the fetus, and Zika virus infection has also been associated with Guillain-Barre syndrome in adults.

Zika virus was first identified in 1947 in the Zika Forest of Uganda and was, for decades, associated only with sporadic, mild human infections across Africa and Asia. This changed with a major outbreak in Yap State, Micronesia, in 2007, followed by a larger epidemic in French Polynesia in 2013-14, and culminating in widespread transmission across the Americas from 2015 onwards. The rapid spread of the virus and its association with congenital abnormalities led the World Health Organization to declare the outbreak a Public Health Emergency of International Concern in February 2016, prompting a substantial global research and public health response.

There is currently no widely licensed antiviral treatment specific for Zika virus infection, and management remains largely supportive, focused on rest, fluids, and symptom relief. Several candidate vaccines, including inactivated, live-attenuated, DNA, mRNA, and viral-vector platforms, have progressed through preclinical and early clinical development, but none has yet achieved full licensure, in part reflecting the marked decline in transmission and case numbers since the peak of the 2015-16 epidemic. Prevention, therefore, continues to rely heavily on vector control, personal protective measures against mosquito bites, and guidance for pregnant women and their partners in areas with known or possible Zika virus transmission.

Overall, Zika virus illustrates how a flavivirus once considered a minor, sporadic pathogen can emerge to cause a major epidemic with severe and unexpected clinical consequences. Its unusual capacity for sexual and vertical transmission, together with its links to congenital and neurological disease, continues to make it an important focus for virology research, diagnostics development, and vaccine and antiviral discovery.