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A Zika virus envelope mutation preceding the 2015 epidemic enhances virulence and fitness for transmission.

ABSTRACT: Arboviruses maintain high mutation rates due to lack of proofreading ability of their viral polymerases, in some cases facilitating adaptive evolution and emergence. Here we show that, just before its 2013 spread to the Americas, Zika virus (ZIKV) underwent an envelope protein V473M substitution (E-V473M) that increased neurovirulence, maternal-to-fetal transmission, and viremia to facilitate urban transmission. A preepidemic Asian ZIKV strain (FSS13025 isolated in Cambodia in 2010) engineered with the V473M substitution significantly increased neurovirulence in neonatal mice and produced higher viral loads in the placenta and fetal heads in pregnant mice. Conversely, an epidemic ZIKV strain (PRVABC59 isolated in Puerto Rico in 2015) engineered with the inverse M473V substitution reversed the pathogenic phenotypes. Although E-V473M did not affect oral infection of Aedes aegypti mosquitoes, competition experiments in cynomolgus macaques showed that this mutation increased its fitness for viremia generation, suggesting adaptive evolution for human viremia and hence transmission. Mechanistically, the V473M mutation, located at the second transmembrane helix of the E protein, enhances virion morphogenesis. Overall, our study revealed E-V473M as a critical determinant for enhanced ZIKV virulence, intrauterine transmission during pregnancy, and viremia to facilitate urban transmission.

SUBMITTER: Shan C

PROVIDER: S-EPMC7443865 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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A Zika virus envelope mutation preceding the 2015 epidemic enhances virulence and fitness for transmission.

Shan Chao C Xia Hongjie H Haller Sherry L SL Azar Sasha R SR Liu Yang Y Liu Jianying J Muruato Antonio E AE Chen Rubing R Rossi Shannan L SL Wakamiya Maki M Vasilakis Nikos N Pei Rongjuan R Fontes-Garfias Camila R CR Singh Sanjay Kumar SK Xie Xuping X Weaver Scott C SC Shi Pei-Yong PY

Proceedings of the National Academy of Sciences of the United States of America 20200803 33

Arboviruses maintain high mutation rates due to lack of proofreading ability of their viral polymerases, in some cases facilitating adaptive evolution and emergence. Here we show that, just before its 2013 spread to the Americas, Zika virus (ZIKV) underwent an envelope protein V473M substitution (E-V473M) that increased neurovirulence, maternal-to-fetal transmission, and viremia to facilitate urban transmission. A preepidemic Asian ZIKV strain (FSS13025 isolated in Cambodia in 2010) engineered w ...[more]

PMID: 32747564

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Project description:BackgroundLocal mosquito-borne Zika virus (ZIKV) transmission has been reported in two counties in the contiguous United States (US), prompting the issuance of travel, prevention, and testing guidance across the contiguous US. Large uncertainty, however, surrounds the quantification of the actual risk of ZIKV introduction and autochthonous transmission across different areas of the US.MethodsWe present a framework for the projection of ZIKV autochthonous transmission in the contiguous US during the 2015-2016 epidemic using a data-driven stochastic and spatial epidemic model accounting for seasonal, environmental, and detailed population data. The model generates an ensemble of travel-related case counts and simulates their potential to have triggered local transmission at the individual level in the 2015-2016 ZIKV epidemic.ResultsWe estimate the risk of ZIKV introduction and local transmission at the county level and at the 0.025° × 0.025° cell level across the contiguous US. We provide a risk measure based on the probability of observing local transmission in a specific location during a ZIKV epidemic modeled after the epidemic observed during the years 2015-2016. The high spatial and temporal resolution of the model allows us to generate statistical estimates of the number of ZIKV introductions leading to local transmission in each location. We find that the risk was spatially heterogeneously distributed and concentrated in a few specific areas that account for less than 1% of the contiguous US population. Locations in Texas and Florida that have actually experienced local ZIKV transmission were among the places at highest risk according to our results. We also provide an analysis of the key determinants for local transmission and identify the key introduction routes and their contributions to ZIKV transmission in the contiguous US.ConclusionsThis framework provides quantitative risk estimates, fully captures the stochasticity of ZIKV introduction events, and is not biased by the under-ascertainment of cases due to asymptomatic cases. It provides general information on key risk determinants and data with potential uses in defining public health recommendations and guidance about ZIKV risk in the US.

Project description:BackgroundZika virus (ZIKV) emerged as a global epidemic in 2015-2016 from Latin America with its true geographical extent remaining unclear due to widely presumed underreporting. The identification of locations with potential and unknown spread of ZIKV is a key yet understudied component for outbreak preparedness. Here, we aim to identify locations at a high risk of cryptic ZIKV spread during 2015-2016 to further the understanding of the global ZIKV epidemiology, which is critical for the mitigation of the risk of future epidemics.MethodsWe developed an importation simulation model to estimate the weekly number of ZIKV infections imported in each susceptible spatial unit (i.e. location that did not report any autochthonous Zika cases during 2015-2016), integrating epidemiological, demographic, and travel data as model inputs. Thereafter, a global risk model was applied to estimate the weekly ZIKV transmissibility during 2015-2016 for each location. Finally, we assessed the risk of onward ZIKV spread following importation in each susceptible spatial unit to identify locations with a high potential for cryptic ZIKV spread during 2015-2016.ResultsWe have found 24 susceptible spatial units that were likely to have experienced cryptic ZIKV spread during 2015-2016, of which 10 continue to have a high risk estimate within a highly conservative scenario, namely, Luanda in Angola, Banten in Indonesia, Maharashtra in India, Lagos in Nigeria, Taiwan and Guangdong in China, Dakar in Senegal, Maputo in Mozambique, Kinshasa in Congo DRC, and Pool in Congo. Notably, among the 24 susceptible spatial units identified, some have reported their first ZIKV outbreaks since 2017, thus adding to the credibility of our results (derived using 2015-2016 data only).ConclusionOur study has provided valuable insights into the potentially high-risk locations for cryptic ZIKV circulation during the 2015-2016 pandemic and has also laid a foundation for future studies that attempt to further narrow this key knowledge gap. Our modelling framework can be adapted to identify areas with likely unknown spread of other emerging vector-borne diseases, which has important implications for public health readiness especially in resource-limited settings.

Project description:BackgroundAfter being eliminated during the 1950s, dengue reemerged in Brazil in the 1980s. Since then, incidence of the disease has increased, as serotypes move within and between cities. The co-circulation of multiple serotypes contributes to cycles of epidemic and interepidemic years, and a seasonal pattern of transmission is observed annually. Little is known regarding possible differences in the epidemiology of dengue under epidemic and interepidemic scenarios. This study addresses this gap and aims to assess the epidemiological characteristics and determinants of epidemic and interepidemic dengue transmission, utilizing data from the 5th largest city in Brazil (Fortaleza), at fine spatial and temporal scales.Methods/principal findingsLongitudinal models of monthly rates of confirmed dengue cases were used to estimate the differential contribution of contextual factors to dengue transmission in Fortaleza between 2011 and 2015. Models were stratified by annual climatological schedules and periods of interepidemic and epidemic transmission, controlling for social, economic, structural, entomological, and environmental factors. Results revealed distinct seasonal patterns between interepidemic and epidemic years, with persistent transmission after June in interepidemic years. Dengue was strongly associated with violence across strata, and with poverty and irregular garbage collection during periods of low transmission, but not with other indicators of public service provision or structural deprivation. Scrapyards and sites associated with tire storage were linked to incidence differentially between seasons, with the strongest associations during transitional precipitation periods. Hierarchical clustering analysis suggests that the dengue burden concentrates in the southern periphery of the city, particularly during periods of minimal transmission.Conclusions/significanceOur findings have direct programmatic implications. Vector control operations must be sustained after June even in non-epidemic years. More specifically, scrapyards and sites associated with tires (strongly associated with incidence during periods of minimal transmission), require sustained entomological surveillance, particularly during interepidemic intervals and in the urban periphery. Intersectoral collaborations that address urban violence are critical for facilitating the regular activities of vector control agents.

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A Zika virus envelope mutation preceding the 2015 epidemic enhances virulence and fitness for transmission.

Publications

A Zika virus envelope mutation preceding the 2015 epidemic enhances virulence and fitness for transmission.

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