Zika virus (ZIKV) is currently taxonomic classified according to the ICTV Online (10th) Report and the last change into Zika virus taxon has occurred in 2018. ZIKV moved to the new higher-level taxa (realm) and has been classified as a member of the realm of Riboviria. ZIKV belongs to the Flaviviridae family, composed of 89 species that infects mainly birds and mammals and is divided into four different genera: Hepacivirus, Pegivirus, Pestivirus and Flavivirus (Consortium, 2018). Most of the 53 known species that constitute the Flavivirus genus are arthropod-borne and many of the described species have veterinary and human importance such as Dengue virus, West Nile virus, Yellow fever virus, Saint Louis encephalitis virus, Japanese encephalitis virus and Zika virus (Simmonds et al., 2017).
ZIKV was initially described in a series of discoveries of unknown viruses in Uganda, by the date, former British protectorate of Uganda. Among those viruses, Semliki Forest virus (Smithburn & Haddow, 1944), Bunyamwera virus (Smithburn, Haddow, & Mahaffy, 1946) and Ntaya virus (Smithburn & Haddow, 1951) were isolated during a collaboration between a British team of Virus Research Institute and researchers of Rockefeller Foundation (Dick, 1953). The first report of ZIKV was published in 1952, when Dick, Kitchen, and Haddow reported two distinct isolation events in time and from different hosts at Zika Forest, Uganda (Dick, Kitchen, & Haddow, 1952). Firstly, in April 1947, ZIKV was isolated from sentinel rhesus monkey (Macaca mulatta) placed in cages at the Zika forest. The second isolation occurred nine months later, in January 1948, from Aedes africanus mosquitoes at the same location (Dick et al., 1952). The virus was named after the coincidence of the isolation place (Zika forest).
A key problem with much of the literature regarding ZIKV early epidemiology is the lack of nucleotide sequences available. After the first full genome sequencing – (strain MR-766) (Kuno & Chang, 2007) and partial genome sequencing out of patients from an outbreak in Yap, Micronesia (Lanciotti et al., 2008) it was possible a reliable proposition of a phylogenetic classification for ZIKV isolates.
The work of Lanciotti and colleagues (2008) has proposed three ZIKV lineages – the Asian, East African and the West African. Nucleotide sequences derived from the NS5 gene (Lanciotti et al., 2008) of CDC/World Health Organization reference collection (strains 41524, 41525 and 41662) isolated from Senegal, in 1984 obtained from Aedes spp. Mosquitoes. A limitation with this study, however, it was the low coverage of the coding region, resulting in the junction of DNA data from 4 patients into a combined consensus sequence – the ZIKV2007 epidemic consensus sequence – (EU545988). Additionally, only the NS5 gene was used to perform phylogenetic analysis.
This has led Haddow and collaborators (2012) to investigate genetic relationships among ZIKV isolates (Haddow et al., 2012). New isolates obtained from the World Reference Center for Emerging Viruses and Arboviruses (WRCEVA) at the University of Texas Medical Branch, allowed the generation of five ORFs (open reading frame) from different countries – Malaysia, Senegal, Uganda, Cambodia and Nigeria – and with a wide range of time, between 1947 and 2010.
After phylogenetic analyses using recently generated and previously available sequences from the NCBI database, Haddow and collaborators (2012) proposed two main viruses’ lineages (African and Asian). From that point, several studies (Faria et al., 2016a, 2016b; Liu et al., 2016; Pettersson et al., 2016; Wang et al., 2016; Zhu et al., 2016) performed phylogenetic analysis that corroborates the hypothesis of two Zika lineages. Although ZIKV cases have been reported in some African countries after 2015, such as Senegal and Nigeria (Herrera et al., 2017) and Guinea Bissau (Rosenstierne et al., 2018), it was not possible to determine their corresponding lineages.
Considering two coding regions (non-structural protein (NS5) and envelope protein (E)), some authors have hypothesized the existence of a sister group of African lineage, the African II lineage (Gong, Gao, & Han, 2016; Shen et al., 2016). However, while no complete genome of the African II lineage has been completely sequenced, this hypothesis cannot be tested.
Virulence of African lineage has been accessed both in vitro and in in vivo. Several in vivo studies (Calvez et al., 2018; Jaeger et al., 2019; Shao et al., 2017; Smith et al., 2018) have shown that African strains cause more damage in embryos of mouse and mosquitoes than Asian strains. Unfortunately, most of these works were restricted to infection at early gestation stages or mouse-adapted models to African MR766 strain or other reference strains. Recently, a study using a porcine foetal transmission model has reinforced the virulence of African lineages in comparison with the Asian (Udenze, Trus, Berube, Gerdts, & Karniychuk, 2019). Infected animals with African strain demonstrated higher viral loads in foetal organs, more in utero infection and more efficient virus transmission between siblings (Udenze et al., 2019).
Regarding patterns of infection, susceptible A129 mice presented different profiles of chemokines, cytokines, growth factors, and other protein mediators when infected with African and Asian strains (Dowall, Graham, & Hewson, 2020). Animals infected with African strain presented severe disease, higher levels of IL-6 and TNF-α, whereas animals infected with Asian strain kept asymptomatic (Dowall et al., 2020). Both strains presented a similar profile of cytokine secretion for IP-10, KC, and MCP-1, but with levels for MCP-1 and KC higher in animals challenged with African strain (Dowall et al., 2020).
