Comparative genomic analysis of pre-epidemic and epidemic Zika virus strains for virological factors potentially associated with the rapidly expanding epidemic

Abstract

Less than 20 sporadic cases of human Zika virus (ZIKV) infection were reported in Africa and Asia before 2007, but large outbreaks involving up to 73% of the populations on the Pacific islands have started since 2007, and spread to the Americas in 2014. Moreover, the clinical manifestation of ZIKV infection has apparently changed, as evident by increasing reports of neurological complications, such as Guillain–Barré syndrome in adults and congenital anomalies in neonates. We comprehensively compared the genome sequences of pre-epidemic and epidemic ZIKV strains with complete genome or complete polyprotein sequences available in GenBank. Besides the reported phylogenetic clustering of the epidemic strains with the Asian lineage, we found that the topology of phylogenetic tree of all coding regions is the same except that of the non-structural 2B (NS2B) coding region. This finding was confirmed by bootscan analysis and multiple sequence alignment, which suggested the presence of a fragment of genetic recombination at NS2B with that of Spondweni virus. Moreover, the representative epidemic strain possesses one large bulge of nine bases instead of an external loop on the first stem-loop structure at the 3′-untranslated region just distal to the stop codon of the NS5 in the 1947 pre-epidemic prototype strain. Fifteen amino acid substitutions are found in the epidemic strains when compared with the pre-epidemic strains. As mutations in other flaviviruses can be associated with changes in virulence, replication efficiency, antigenic epitopes and host tropism, further studies would be important to ascertain the biological significance of these genomic changes.

The Epidemic that Shook the World—The Zika Virus Rampage

“…42 Lanciotti et al 45 have shown that the Uganda MR766 ZIKV and the Yap Island Zika strains have 96% conservancy in their protein sequences, which the authors suggest could be the result of selective pressures arising from virus replication adapted to vertebrate hosts and arthropod vectors. This is also borne out by the Ka/Ks (asynonymous to synonymous) ratios for the various coding regions of ZIKV computed by Zhu et al 35 which showed that these ratios for ZIKV strains were comparatively low, implying that these genes were under stabilizing selection pressure. Note, however, the observations of Giri et al 46 from their study of the ZIKV proteome (strain MR766) that revealed abundant intrinsically disordered regions in the capsid, NS2B, NS3, NS4A and NS5 proteins …”

“…Freire et al 38 also observed high levels of secretion of NS4A proteins, like for NS1 proteins, by infected cells, which they believe is significant since both NS1 and NS4A play important roles in viral replication, while NS4A helps viral survival by inhibiting cell death by up-regulation. Zhu et al 35 suggest that NS1 is required to initiate RNA genome synthesis.…”

“…35 The 10 structural and NS proteins contain multiple transmembrane domains, with the majority being accounted for by NS2A, NS2B, NS4A and NS4B. 35 A 2K protein is generated by cleavage at the signal sequence of the NS4B; Kuno and Chang has discussed the cleavage sites in ZIKV and related other viral genomes in detail.…”

“…35 The 10 structural and NS proteins contain multiple transmembrane domains, with the majority being accounted for by NS2A, NS2B, NS4A and NS4B. 35 A 2K protein is generated by cleavage at the signal sequence of the NS4B; Kuno and Chang has discussed the cleavage sites in ZIKV and related other viral genomes in detail. 34 The different genes encoding for the proteins making up the ZIKV play important roles in viral pathogenicity, replication and assembly, some of which are briefly described below.…”

Exploitation of Glycobiology in Anti-Adhesion Approaches against Biothreat Agents

“…The virus projects a glycosylation site outward and glycans are attached to the viral protein surface at this site. Thus, differences in carbohydrate molecules in this region may influence virus transmission and explain its tissue tropism or variable disease progression in different parts of the world [72]. Furthermore, glycosylation is a promising investigation target in context of potential receptors for anti-adhesive therapies.…”