Diversity of and Implications from the Viral Genomes and Viral Proteins of Zika Virus

Zika virus (ZIKV) belongs to the Genus Flavivirus of Family Flaviviridae and is closely related to Dengue, West Nile, Japanese encephalitis and yellow fever viruses. Since 2007 ZIKV has caused a series of epidemics in Micronesia, the South Pacific, and, most recently, the Americas. Infection with ZIKV is likely linked to severe medical sequelae. Most recently, it has been observed that ZIKV infection is probably associated with microcephaly of neonates and this makes it urgent to investigate every aspect of the virus including its natural history, epidemiology, pathogenesis and interactions with hosts. In the present study, we analyzed the nucleotide acid (NA) and amino acid (Aa) sequences of the strains of Zika viruses responsible for the seven different epidemics. Sequence alignments and phylogenetic analysis revealed that the ZIKV can be divided into African and Asian types. Interestingly, we found that the Malaysia strain isolated in 1966 appears more divergent from other Asian strains and less divergent from the African type than other Asian strains. To understand why the recent ZIKV outbreak correlates with microcephaly in neonates, we analyzed the diversity of amino acid sequences between the French Polynesia (FP) strain and the Brazil strain. We found that they are more closely related to each other than to other strains being studied. This is consistent with the hypothesis of Brazil ZIKV being evolved from FP-type ancestors. Notably, there were 11 amino acid residues in the Brazil 2016 strain that were different from the consensus sequence. Further analysis of sequence divergence in individual proteins showed that the biggest difference between the FP strain and Brazil strain lies within the NS1 protein, which is related to neurovirulence as in the Dengue virus. Therefore, NS1 might be an important target for further investigation.