Unravelling the epidemiological diversity of Zika virus by analyzing key protein variations

Abstract

Abstract The consequences of Zika virus (ZIKV) infections were limited to sporadic mild diseases until almost a decade ago, when epidemics outbreaks took place and were followed by virus introduction and quick spread into the Americas. Simultaneously, novel severe neurological manifestations for ZIKV infections were identified, including congenital microcephaly. However, the complete understanding of why the epidemic strains behave differently from previously circulating variants is still missed and many questions still remain about the actual significance of ZIKV genetic variations in the epidemiology and biology of ZIKV. Here, we attained to analyze a high number of sequences to identify genes with different levels of variability and patterns of genomic variations that could be associated with ZIKV diversity. We compared numerous epidemic strains with the pre-epidemic ones from both the Asian and the African lineages, while we also investigated special variations among the epidemic ZIKV strains derived from microcephaly cases. We identified several viral genes with dissimilar mutation rates among the ZIKV strain groups. Moreover, we found novel protein variation profiles that might be associated with the epidemiological particularities of each category of ZIKV strains. Finally, we assessed the impact of the detected changes on the structure and stability of the corresponding viral proteins, finding some interesting non synonymous variations which could help to explain the heterogeneous features among the diverse ZIKA strains. Altogether, this work contributes to identify ZIKV genetic variations that might have a phenotypical impact, as a basis for future experimental analysis to elucidate the recent ZIKV emergency.