Inter- and intra-lineage genetic diversity of wild-type Zika viruses reveals both common and distinctive nucleotide variants and clusters of genomic diversity

Natalie D Collins,Steven G Widen,Li Li,Daniele M Swetnam,Pei-Yong Shi,Robert B Tesh,Vanessa V Sarathy

doi:10.1080/22221751.2019.1645572

Abstract

ABSTRACT Zika virus (ZIKV) strains belong to the East African, West African, and Asian/American phylogenetic lineages. RNA viruses, like ZIKV, exist as populations of genetically-related sequences whose heterogeneity may impact viral fitness, evolution, and virulence. Genetic diversity of representative ZIKVs from each lineage was examined using next generation sequencing (NGS) paired with downstream entropy and single nucleotide variant (SNV) analysis. Comparisons showed that inter-lineage diversity was statistically supported, while intra-lineage diversity varied. Intra-lineage diversity was significant for East but not West Africa strains. Furthermore, intra-lineage diversity for the Asian/American lineage was not supported for human serum isolates; however, a placenta isolate differed significantly. Relative entropy values were higher in the pre-membrane/membrane (prM/M) gene of several ZIKV strains. Additionally, the East African lineage contained a greater number of synonymous SNVs, while a greater number of non-synonymous SNVs were identified for American strains. Further, inter-lineage SNVs were dispersed throughout the genome, whereas intra-lineage non-synonymous SNVs for Asian/American strains clustered within prM/M and NS1 gene. This comprehensive analysis of ZIKV genetic diversity provides a repository of SNV positions across lineages. We posit that increased non-synonymous SNV populations and increased relative genetic diversity of the prM/M and NS1 proteins provides more evidence for their role in ZIKV virulence and fitness.

Highlights

Zika virus (ZIKV) is a mosquito-borne flavivirus that was originally discovered in Uganda in 1947 after a sentinelRhesus monkey developed fever and viremia [1]
The present study evaluated genetic diversity across lineages of ZIKV analysing next generation sequencing (NGS) of representative strains from various sources, including a human placenta isolate
The mean genomic diversity of the Asian/ American lineage was higher than those of the African lineages, and American isolates had a greater number of high entropy positions (Figure 3a-c and S3)

Summary

Introduction

Zika virus (ZIKV) is a mosquito-borne flavivirus that was originally discovered in Uganda in 1947 after a sentinel. RNA virus genomes exist as viral populations composed of genetically-related sequences. This is due, in part, to the error rate of the RdRp, which leads to nucleotide misincorporation during viral replication. Generation sequencing (NGS) provides a platform to gain deeper understanding of viral diversity by increasing the depth of sequencing coverage, thereby allowing detection of single nucleotide variants (SNV) in the population. NGS has been used to gain insight into the genetic diversity of representative ZIKV strains from different lineages. Relative genomic diversity was highest in the prM/M and NS1 gene regions of Asian/American strains isolated from human serum. This study provides insight into the intra-host diversity of contemporary ZIKV that may contribute to mammalian infection or virulence

Materials and methods

Results

Discussion