Time-scaled phylogeography of complete Zika virus genomes using discrete and continuous space diffusion models

Zika virus (ZIKV), a vector-borne infectious agent that has recently been associated with neurological diseases and congenital microcephaly, was first reported in the Western hemisphere in early 2015. A number of authors have reconstructed its epidemiological history using advanced phylogenetic approaches, and the majority of Zika phylogeography studies have used discrete diffusion models. Continuous space diffusion models make it possible to infer the possible origin of the virus in real space by reconstructing its ancestral location on the basis of geographical coordinates deduced from the latitude and longitude of the sampling locations. We analysed all the ZIKV complete genome isolates whose sampling times and localities were available in public databases at the time the study began, using a Bayesian approach for discrete and continuous phylogeographic reconstruction. The discrete phylogeographic analysis suggested that ZIKV emerged to become endemic/epidemic in the first decade of the 1900s in the Ugandan rainforests, and then reached Western Africa and Asia between the 1930s and 1950s. After a long period of about 40 years, it spread to the Pacific islands and reached Brazil from French Polynesia. Continuous phylogeography of the American epidemic showed that the virus entered in north-eastern Brazil in late 2012 and started to spread in early 2013 from two high probability regions: one corresponding to the entire north-east Brazil and the second surrounding the city of Rio de Janeiro, in a mainly northwesterly direction to Central America, the north-western countries of south America and the Caribbean islands. Our data suggest its cryptic circulation in both French Polynesia and Brazil, thus raising questions about the mechanisms underlying its undetected persistence in the absence of a known animal reservoir, and underline the importance of continuous diffusion models in making more reliable phylogeographic reconstructions of emerging viruses.