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Role of mutational reversions and fitness restoration in Zika virus spread to the Americas.

ABSTRACT: Zika virus (ZIKV) emerged from obscurity in 2013 to spread from Asia to the South Pacific and the Americas, where millions of people were infected, accompanied by severe disease including microcephaly following congenital infections. Phylogenetic studies have shown that ZIKV evolved in Africa and later spread to Asia, and that the Asian lineage is responsible for the recent epidemics in the South Pacific and Americas. However, the reasons for the sudden emergence of ZIKV remain enigmatic. Here we report evolutionary analyses that revealed four mutations, which occurred just before ZIKV introduction to the Americas, represent direct reversions of previous mutations that accompanied earlier spread from Africa to Asia and early circulation there. Our experimental infections of Aedes aegypti mosquitoes, human cells, and mice using ZIKV strains with and without these mutations demonstrate that the original mutations reduced fitness for urban, human-amplifed transmission, while the reversions restored fitness, increasing epidemic risk. These findings include characterization of three transmission-adaptive ZIKV mutations, and demonstration that these and one identified previously restored fitness for epidemic transmission soon before introduction into the Americas. The initial mutations may have followed founder effects and/or drift when the virus was introduced decades ago into Asia.

SUBMITTER: Liu J

PROVIDER: S-EPMC7838395 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Role of mutational reversions and fitness restoration in Zika virus spread to the Americas.

Liu Jianying J Liu Yang Y Shan Chao C Nunes Bruno T D BTD Yun Ruimei R Haller Sherry L SL Rafael Grace H GH Azar Sasha R SR Andersen Clark R CR Plante Kenneth K Vasilakis Nikos N Shi Pei-Yong PY Weaver Scott C SC

Nature communications 20210126 1

Zika virus (ZIKV) emerged from obscurity in 2013 to spread from Asia to the South Pacific and the Americas, where millions of people were infected, accompanied by severe disease including microcephaly following congenital infections. Phylogenetic studies have shown that ZIKV evolved in Africa and later spread to Asia, and that the Asian lineage is responsible for the recent epidemics in the South Pacific and Americas. However, the reasons for the sudden emergence of ZIKV remain enigmatic. Here w ...[more]

PMID: 33500409

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Project description:BackgroundMosquito-borne and sexually transmitted Zika virus has become widespread across Central and South America and the Caribbean. Many Zika vaccine candidates are under active development.ObjectiveTo quantify the effect of Zika vaccine prioritization of females aged 9 to 49 years, followed by males aged 9 to 49 years, on incidence of prenatal Zika infections.DesignA compartmental model of Zika transmission between mosquitoes and humans was developed and calibrated to empirical estimates of country-specific mosquito density. Mosquitoes were stratified into susceptible, exposed, and infected groups; humans were stratified into susceptible, exposed, infected, recovered, and vaccinated groups. Age-specific fertility rates, Zika sexual transmission, and country-specific demographics were incorporated.Setting34 countries and territories in the Americas with documented Zika outbreaks.Target populationMales and females aged 9 to 49 years.InterventionAge- and sex-targeted immunization using a Zika vaccine with 75% efficacy.MeasurementsAnnual prenatal Zika infections.ResultsFor a base-case vaccine efficacy of 75% and vaccination coverage of 90%, immunizing females aged 9 to 49 years (the World Health Organization target population) would reduce the incidence of prenatal infections by at least 94%, depending on the country-specific Zika attack rate. In regions where an outbreak is not expected for at least 10 years, vaccination of women aged 15 to 29 years is more efficient than that of women aged 30 years or older.LimitationPopulation-level modeling may not capture all local and neighborhood-level heterogeneity in mosquito abundance or Zika incidence.ConclusionA Zika vaccine of moderate to high efficacy may virtually eliminate prenatal infections through a combination of direct protection and transmission reduction. Efficiency of age-specific targeting of Zika vaccination depends on the timing of future outbreaks.Primary funding sourceNational Institutes of Health.

Project description:BackgroundAn unprecedented Zika virus epidemic occurred in the Americas during 2015-2016. The size of the epidemic in conjunction with newly recognized health risks associated with the virus attracted significant attention across the research community. Our study complements several recent studies which have mapped epidemiological elements of Zika, by introducing a newly proposed methodology to simultaneously estimate the contribution of various risk factors for geographic spread resulting in local transmission and to compute the risk of spread (or re-introductions) between each pair of regions. The focus of our analysis is on the Americas, where the set of regions includes all countries, overseas territories, and the states of the US.Methodology/principal findingsWe present a novel application of the Generalized Inverse Infection Model (GIIM). The GIIM model uses real observations from the outbreak and seeks to estimate the risk factors driving transmission. The observations are derived from the dates of reported local transmission of Zika virus in each region, the network structure is defined by the passenger air travel movements between all pairs of regions, and the risk factors considered include regional socioeconomic factors, vector habitat suitability, travel volumes, and epidemiological data. The GIIM relies on a multi-agent based optimization method to estimate the parameters, and utilizes a data driven stochastic-dynamic epidemic model for evaluation. As expected, we found that mosquito abundance, incidence rate at the origin region, and human population density are risk factors for Zika virus transmission and spread. Surprisingly, air passenger volume was less impactful, and the most significant factor was (a negative relationship with) the regional gross domestic product (GDP) per capita.Conclusions/significanceOur model generates country level exportation and importation risk profiles over the course of the epidemic and provides quantitative estimates for the likelihood of introduced Zika virus resulting in local transmission, between all origin-destination travel pairs in the Americas. Our findings indicate that local vector control, rather than travel restrictions, will be more effective at reducing the risks of Zika virus transmission and establishment. Moreover, the inverse relationship between Zika virus transmission and GDP suggests that Zika cases are more likely to occur in regions where people cannot afford to protect themselves from mosquitoes. The modeling framework is not specific for Zika virus, and could easily be employed for other vector-borne pathogens with sufficient epidemiological and entomological data.

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Role of mutational reversions and fitness restoration in Zika virus spread to the Americas.

Publications

Role of mutational reversions and fitness restoration in Zika virus spread to the Americas.

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