When health officials confirmed the first locally acquired Zika cases in the continental United States in Miami in July 2016, they knew in a general way how the mosquito–borne virus probably arrived.

The Aedes aegypti mosquitoes that serve as the vector between Zika and humans are present in Miami, but their range is limited — they don’t travel farther than about 1½ football fields. Tourists do.

Since none of the Florida cases involved people who had visited an affected country or had sex with someone who did, a traveler must have introduced the virus to local mosquitoes after being bitten abroad and then again in Miami.

Now a new study by a large group of international researchers sheds more light on how and when that happened. The study found the virus was introduced into Miami in 2016 at least four and up to 40 separate times, with most of the viral lineages from strains found in the Caribbean.

Co–led by scientists at Fred Hutchinson Cancer Research Center, researchers sequenced the genomes from infected patients and mosquitoes from different times in the Miami outbreak — which reached about 250 cases – and created a phylogenetic tree, or genetic history, of the viruses.

“By working with the genome sequences, we were able to figure out how closely related these cases were and how many introduction events there were,” said Fred Hutch evolutionary biologist Dr. Trevor Bedford, one of more than 60 scientists who contributed to the study. The study was co–led by researchers from The Scripps Research Institute, the U.S. Army Medical Research Institute of Infectious Diseases, Florida Gulf Coast University, the University of Oxford, the Florida Department of Health and the Broad Institute of MIT and Harvard.

The Miami research was one of three related studies published in the journal Nature that analyzed Zika transmission and evolution using genomic sequencing. In the two others:

• A team led by researchers at the Broad Institute traced the virus’s movement from its arrival in Brazil in 2013 to Honduras, Columbia, Puerto Rico, other Caribbean islands and the continental United States.
• A team led by British and Brazilian researchers focused on northeastern Brazil, where the virus first entered the Americas from the Pacific islands. Scientists from around the world converged on the hard–hit region for a road trip by bus – a mobile genomics lab.

A fourth study published in the journal Nature Protocols detailed the technologies used by all the research teams.