It was first discovered in animals in the Florida area, where it is spread in part by local species of Aedes mosquitoes.

In 1964, a case of human infection, producing minor symptoms of a rash and fever, was circumstantially diagnosed.

[4] The virus has been subsequently observed along the eastern and southern coastline of the United States, from Boston through Texas.

Infection in humans is believed to be widespread, based on a 1972 report detecting Keystone virus antibodies in 19–21 percent of the people tested in the Tampa Bay region.

[8] Identification took almost two years after the case actually occurred, when blood samples taken from the subject in 2016 were analyzed retrospectively by researchers studying the incidence of Zika virus in the Florida population.