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Tracing the origin of the NS1 A188V substitution responsible for recent enhancement of Zika virus Asian genotype infectivity.

ABSTRACT: A recent study showed that infectivity of Zika virus (ZIKV) Asian genotype was enhanced by an alanine-to-valine amino acid substitution at residue 188 of the NS1 protein, but the precise time and location of origin of this mutation were not formally estimated. Here, we applied a Bayesian coalescent-based framework to estimate the age and location of the ancestral viral strain carrying the A188V substitution. Our results support that the ancestral ZIKV strain carrying the A188V substitution arose in Southeastern Asia at the early 2000s and circulated in that region for some time (5-10 years) before being disseminated to Southern Pacific islands and the Americas.

SUBMITTER: Delatorre E

PROVIDER: S-EPMC5661894 | biostudies-other | 2017 Nov

REPOSITORIES: biostudies-other

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Tracing the origin of the NS1 A188V substitution responsible for recent enhancement of Zika virus Asian genotype infectivity.

Delatorre Edson E Mir Daiana D Bello Gonzalo G

Memorias do Instituto Oswaldo Cruz 20170904 11

A recent study showed that infectivity of Zika virus (ZIKV) Asian genotype was enhanced by an alanine-to-valine amino acid substitution at residue 188 of the NS1 protein, but the precise time and location of origin of this mutation were not formally estimated. Here, we applied a Bayesian coalescent-based framework to estimate the age and location of the ancestral viral strain carrying the A188V substitution. Our results support that the ancestral ZIKV strain carrying the A188V substitution arose ...[more]

PMID: 28876359

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Project description:Zika virus (ZIKV) is a positive-sense single-stranded RNA virus in the Flaviviridae, which is classified into two different lineages Asian and African. The outbreak of ZIKV Asian lineage isolates in 2015-2016 is associated with the increase in cases with prenatal microcephaly and Guillain-Barré syndrome, and has sparked attention throughout the world. Genome sequence alignment and the analysis of Asian and African lineage isolates indicate that amino acid changes, particular in positively charged amino acid substitutions in the pr region of prM protein might involve a phenotypic change that links with the global outbreak of ZIKV Asian-lineage. The study generated and characterized the virological properties of wild type and mutants of single-round infectious particles (SRIPs) and infectious clones (i.c.s) of ZIKV Asian-lineage Natal RGN strain, and then identified the function of amino acid substitutions at the positions 139 [Asn139→Ser139 (N139S)] and 143 [Glu143→Lys143 (E143K)] in ZIKV polyproteins (located within the pr region of prM protein) in the infectivity and cytopathogenicity. The E143K SRIP and i.c. of Natal RGN strain exhibited relatively higher levels of cytopathic effect, EGFP reporter, viral RNA and protein synthesis, and virus yield in three types of human cell lines, TE617, SF268 and HMC3, compared to wild type (WT), N139S SRIPs and i.c.s, which displayed more efficiency in replication kinetics. Additionally, E143K Natal RGN i.c. had greater activities of virus attachment and entry, yielded higher titers of intracellular and extracellular virions, and assembled the E proteins near to the plasma membrane in infected cells than the other i.c.s. The results indicate that the positively charged amino acid residue Lys143, a conserved residue in the pr region of prM of ZIKV African lineages, plays a crucial role in viral replication kinetics, including viral attachment, entry, assembly and egress. Thus, the negatively charged amino acid residue Glu143 within the pr region of prM leads to an alteration of the phenotypes, in particular, a lower replication efficiency of ZIKV Asian-lineage isolates with the attenuation of infectivity and cytopathicity.

Dataset Information

Tracing the origin of the NS1 A188V substitution responsible for recent enhancement of Zika virus Asian genotype infectivity.

Publications

Tracing the origin of the NS1 A188V substitution responsible for recent enhancement of Zika virus Asian genotype infectivity.

Similar Datasets

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