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1.
Nat Commun ; 12(1): 2290, 2021 04 16.
Article in English | MEDLINE | ID: mdl-33863888

ABSTRACT

Arthropod-borne viruses pose a major threat to global public health. Thus, innovative strategies for their control and prevention are urgently needed. Here, we exploit the natural capacity of viruses to generate defective viral genomes (DVGs) to their detriment. While DVGs have been described for most viruses, identifying which, if any, can be used as therapeutic agents remains a challenge. We present a combined experimental evolution and computational approach to triage DVG sequence space and pinpoint the fittest deletions, using Zika virus as an arbovirus model. This approach identifies fit DVGs that optimally interfere with wild-type virus infection. We show that the most fit DVGs conserve the open reading frame to maintain the translation of the remaining non-structural proteins, a characteristic that is fundamental across the flavivirus genus. Finally, we demonstrate that the high fitness DVG is antiviral in vivo both in the mammalian host and the mosquito vector, reducing transmission in the latter by up to 90%. Our approach establishes the method to interrogate the DVG fitness landscape, and enables the systematic identification of DVGs that show promise as human therapeutics and vector control strategies to mitigate arbovirus transmission and disease.


Subject(s)
Antiviral Agents/administration & dosage , Defective Viruses/genetics , Mosquito Vectors/drug effects , Zika Virus Infection/drug therapy , Zika Virus/genetics , Aedes/drug effects , Aedes/virology , Animals , Chlorocebus aethiops , Computational Biology , Directed Molecular Evolution , Disease Models, Animal , Female , Genetic Fitness , Genome, Viral/genetics , HEK293 Cells , Humans , Mice , Mosquito Control/methods , Mosquito Vectors/virology , Open Reading Frames/genetics , RNA, Viral/genetics , Vero Cells , Zika Virus Infection/transmission , Zika Virus Infection/virology
2.
PLoS Negl Trop Dis ; 15(3): e0009259, 2021 03.
Article in English | MEDLINE | ID: mdl-33705409

ABSTRACT

Dengue, Zika and chikungunya are diseases of global health significance caused by arboviruses and transmitted by the mosquito Aedes aegypti, which is of worldwide circulation. The arrival of the Zika and chikungunya viruses to South America increased the complexity of transmission and morbidity caused by these viruses co-circulating in the same vector mosquito species. Here we present an integrated analysis of the reported arbovirus cases between 2007 and 2017 and local climate and socio-economic profiles of three distinct Colombian municipalities (Bello, Cúcuta and Moniquirá). These locations were confirmed as three different ecosystems given their contrasted geographic, climatic and socio-economic profiles. Correlational analyses were conducted with both generalised linear models and generalised additive models for the geographical data. Average temperature, minimum temperature and wind speed were strongly correlated with disease incidence. The transmission of Zika during the 2016 epidemic appeared to decrease circulation of dengue in Cúcuta, an area of sustained high incidence of dengue. Socio-economic factors such as barriers to health and childhood services, inadequate sanitation and poor water supply suggested an unfavourable impact on the transmission of dengue, Zika and chikungunya in all three ecosystems. Socio-demographic influencers were also discussed including the influx of people to Cúcuta, fleeing political and economic instability from neighbouring Venezuela. Aedes aegypti is expanding its range and increasing the global threat of these diseases. It is therefore vital that we learn from the epidemiology of these arboviruses and translate it into an actionable local knowledge base. This is even more acute given the recent historical high of dengue cases in the Americas in 2019, preceding the COVID-19 pandemic, which is itself hampering mosquito control efforts.


Subject(s)
Chikungunya Fever/epidemiology , Dengue/epidemiology , Zika Virus Infection/epidemiology , Aedes/physiology , Aedes/virology , Animals , Chikungunya Fever/economics , Chikungunya Fever/virology , Chikungunya virus/physiology , Climate , Colombia/epidemiology , Dengue/economics , Dengue/virology , Dengue Virus/physiology , Ecosystem , Humans , Mosquito Vectors/physiology , Mosquito Vectors/virology , South America , Temperature , Zika Virus/physiology , Zika Virus Infection/economics , Zika Virus Infection/virology
3.
Nat Commun ; 12(1): 1810, 2021 03 22.
Article in English | MEDLINE | ID: mdl-33753725

ABSTRACT

For most pathogens, transmission is driven by interactions between the behaviours of infectious individuals, the behaviours of the wider population, the local environment, and immunity. Phylogeographic approaches are currently unable to disentangle the relative effects of these competing factors. We develop a spatiotemporally structured phylogenetic framework that addresses these limitations by considering individual transmission events, reconstructed across spatial scales. We apply it to geocoded dengue virus sequences from Thailand (N = 726 over 18 years). We find infected individuals spend 96% of their time in their home community compared to 76% for the susceptible population (mainly children) and 42% for adults. Dynamic pockets of local immunity make transmission more likely in places with high heterotypic immunity and less likely where high homotypic immunity exists. Age-dependent mixing of individuals and vector distributions are not important in determining spread. This approach provides previously unknown insights into one of the most complex disease systems known and will be applicable to other pathogens.


Subject(s)
Algorithms , Dengue Virus/genetics , Dengue/transmission , Models, Theoretical , Adult , Aedes/virology , Animals , Child , Dengue/epidemiology , Dengue/virology , Dengue Virus/classification , Dengue Virus/physiology , Genome, Viral/genetics , Host-Pathogen Interactions , Humans , Mosquito Vectors/virology , Phylogeny , Phylogeography/methods , Phylogeography/statistics & numerical data , Population Dynamics , Thailand/epidemiology
4.
Nat Commun ; 12(1): 916, 2021 02 10.
Article in English | MEDLINE | ID: mdl-33568638

ABSTRACT

The global emergence of Zika virus (ZIKV) revealed the unprecedented ability for a mosquito-borne virus to cause congenital birth defects. A puzzling aspect of ZIKV emergence is that all human outbreaks and birth defects to date have been exclusively associated with the Asian ZIKV lineage, despite a growing body of laboratory evidence pointing towards higher transmissibility and pathogenicity of the African ZIKV lineage. Whether this apparent paradox reflects the use of relatively old African ZIKV strains in most laboratory studies is unclear. Here, we experimentally compare seven low-passage ZIKV strains representing the recently circulating viral genetic diversity. We find that recent African ZIKV strains display higher transmissibility in mosquitoes and higher lethality in both adult and fetal mice than their Asian counterparts. We emphasize the high epidemic potential of African ZIKV strains and suggest that they could more easily go unnoticed by public health surveillance systems than Asian strains due to their propensity to cause fetal loss rather than birth defects.


Subject(s)
Zika Virus Infection/mortality , Zika Virus Infection/virology , Zika Virus/physiology , Zika Virus/pathogenicity , Aedes/physiology , Aedes/virology , Africa , Animals , Asia , Female , Humans , Male , Mice , Phylogeny , Virulence , Zika Virus/classification , Zika Virus/genetics , Zika Virus Infection/transmission
5.
Nursing (Säo Paulo) ; 24(273): 5229-5242, fev.2021.
Article in Portuguese | LILACS, BDENF - Nursing | ID: biblio-1148490

ABSTRACT

Objetivo: descrever incidência de dengue em Santos/SP e relacionar coeficiente de incidência (CI) de dengue com indicadores socioeconômicos e entomológicos de 2012-2016. Método: estudo epidemiológico, descritivo, ecológico dos casos confirmados de dengue, residentes em Santos, de 2012-2016, do Sistema de Informação de Agravos de Notificação-Online; foram obtidos seis indicadores socioeconômicos da base de setores censitários do Instituto Brasileiro de Geografia e Estatística-2010; o sétimo do Índice Paulista de Vulnerabilidade Social-2010 e os indicadores entomológicos da Secretaria de Saúde; foi aplicada Correlação bivariada de Spearman (SPSS-Statistics®). Aprovado pelo Comitê de Ética em Pesquisa-CAAE nº79776017.1.0000.5479. Resultados: de 2012-2016 ocorreram 16.451 casos, com CI de 117,4 (2012) a 2.122,8 (2013) casos/100.000 habitantes, maior no sexo feminino e de 15-29 anos; os fatores socioeconômicos foram mais significativos entre 2015-2016; o Índice de Densidade de fêmeas Aedes aegypti apresentou maior correlação positiva. Conclusão: descreveu-se perfil epidemiológico/entomológico da dengue, apoiando gestores nas ações locais de controle.(AU)


Objectives: describe incidence of dengue in Santos/SP and relate dengue incidence coefficient (IC) with socioeconomic and entomological indicators from 2012-2016. Methods: epidemiological, descriptive, ecological study of confirmed cases of dengue, resident in Santos, from 2012-2016, of the Online-Notifiable Diseases Information System; six socioeconomic indicators were obtained from census sectors base of Brazilian Institute of Geography and Statistics-2010; the seventh from the São Paulo Index of Social Vulnerability-2010 and the entomological indicators from the Health Department; Spearman's Bivariate Correlation (SPSS-Statistics®) was applied. Approved by the Research Ethics Committee-CAAE nº79776017.1.0000.5479. Results: from 2012-2016 there were 16.451 cases, with IC from 117,4 (2012) to 2.122,8 (2013) cases/100.000 inhabitants, higher in females and between 15-29 years old; socioeconomic factors were more significant between 2015-2016; the Density Index of Aedes aegypti females showed a greater positive correlation. Conclusion: epidemiological/entomological profile of dengue was described, supporting managers in local control actions.(AU)


Objetivos: describir incidencia del dengue en Santos/SP y relacionar coeficiente de incidencia (CI) del dengue con indicadores socioeconómicos y entomológicos para 2012-2016. Métodos: estudio epidemiológico, descriptivo, ecológico de casos confirmados de dengue, residentes en Santos, desde 2012-2016, del Sistema de Información de Enfermedades de Notificación-Online; obtuvieron-se seis indicadores socioeconómicos desde base de sectores censales del Instituto Brasileño de Geografía y Estadística-2010, el séptimo del Índice de Vulnerabilidad Social de São Paulo-2010 y los indicadores entomológicos del Departamento de Salud. Aplicó-se Correlación Bivariada de Spearman (SPSS-Statistics®). Aprobado por el Comité de Ética en Investigación-CAAE nº79776017.1.0000.5479. Resultados: desde 2012-2016 hubo 16.451 casos, con CI de 117,4 (2012) a 2.122,8 (2013) casos/100.000 habitantes, mayor en mujeres y de 15-29 años; los factores socioeconómicos fueron más significativos entre 2015-2016; el Índice de Densidad de hembras Aedes aegypti mostró mayor correlación positiva. Conclusión: describió-se perfil epidemiológico/entomológico del dengue, apoyando a los gerentes en acciones de control local.(AU)


Subject(s)
Humans , Public Health Nursing , Health Profile , Incidence , Aedes/virology , Dengue/epidemiology , Social Vulnerability Index , Socioeconomic Factors , Disaster Vulnerability/statistics & numerical data , Entomology
6.
Mem Inst Oswaldo Cruz ; 115: e200313, 2021.
Article in English | MEDLINE | ID: mdl-33533870

ABSTRACT

BACKGROUND: Aedes aegypti is the sole vector of urban arboviruses in French Guiana. Overtime, the species has been responsible for the transmission of viruses during yellow fever, dengue, chikungunya and Zika outbreaks. Decades of vector control have produced resistant populations to deltamethrin, the sole molecule available to control adult mosquitoes in this French Territory. OBJECTIVES: Our surveillance aimed to provide public health authorities with data on insecticide resistance in Ae. aegypti populations and other species of interest in French Guiana. Monitoring resistance to the insecticide used for vector control and to other molecule is a key component to develop an insecticide resistance management plan. METHODS: In 2009, we started to monitor resistance phenotypes to deltamethrin and target-site mechanisms in Ae. aegypti populations across the territory using the WHO impregnated paper test and allelic discrimination assay. FINDINGS: Eight years surveillance revealed well-installed resistance and the dramatic increase of alleles on the sodium voltage-gated gene, known to confer resistance to pyrethroids (PY). In addition, we observed that populations were resistant to malathion (organophosphorous, OP) and alpha-cypermethrin (PY). Some resistance was also detected to molecules from the carbamate family. Finally, those populations somehow recovered susceptibility against fenitrothion (OP). In addition, other species distributed in urban areas revealed to be also resistant to pyrethroids. CONCLUSION: The resistance level can jeopardize the efficiency of chemical adult control in absence of other alternatives and conducts to strongly rely on larval control measures to reduce mosquito burden. Vector control strategies need to evolve to maintain or regain efficacy during epidemics.


Subject(s)
Aedes/drug effects , Insect Vectors/genetics , Insecticide Resistance/genetics , Insecticides/pharmacology , Mosquito Vectors/drug effects , Pyrethrins/pharmacology , Aedes/genetics , Aedes/virology , Animals , French Guiana , Insect Vectors/drug effects , Mosquito Control/methods , Mosquito Vectors/virology , Spatio-Temporal Analysis
7.
Nat Commun ; 12(1): 595, 2021 01 26.
Article in English | MEDLINE | ID: mdl-33500409

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.


Subject(s)
Epidemics , Evolution, Molecular , Genetic Fitness , Zika Virus Infection/epidemiology , Zika Virus/genetics , Aedes/virology , Africa/epidemiology , Americas/epidemiology , Amino Acid Substitution , Animals , Asia/epidemiology , Cell Line , Disease Models, Animal , Female , Fibroblasts , Humans , Keratinocytes , Mice , Mutation , Phylogeny , Primary Cell Culture , Urban Health/statistics & numerical data , Zika Virus/pathogenicity , Zika Virus Infection/transmission , Zika Virus Infection/virology
8.
PLoS Negl Trop Dis ; 15(1): e0009005, 2021 01.
Article in English | MEDLINE | ID: mdl-33465098

ABSTRACT

BACKGROUND: The integration of house-screening and long-lasting insecticidal nets, known as insecticide-treated screening (ITS), can provide simple, safe, and low-tech Aedes aegypti control. Cluster randomised controlled trials in two endemic localities for Ae. aegypti of south Mexico, showed that ITS conferred both, immediate and sustained (~2 yr) impact on indoor-female Ae. aegypti infestations. Such encouraging results require further validation with studies quantifying more epidemiologically-related endpoints, including arbovirus infection in Ae. aegypti. We evaluated the efficacy of protecting houses with ITS on Ae. aegypti infestation and arbovirus infection during a Zika outbreak in Merida, Yucatan, Mexico. METHODOLOGY/PRINCIPAL FINDINGS: A two-arm cluster-randomised controlled trial evaluated the entomological efficacy of ITS compared to the absence of ITS (with both arms able to receive routine arbovirus vector control) in the neighbourhood Juan Pablo II of Merida. Cross-sectional entomological surveys quantified indoor adult mosquito infestation and arbovirus infection at baseline (pre-ITS installation) and throughout two post-intervention (PI) surveys spaced at 6-month intervals corresponding to dry/rainy seasons over one year (2016-2017). Household-surveys assessed the social reception of the intervention. Houses with ITS were 79-85% less infested with Aedes females than control houses up to one-year PI. A similar significant trend was observed for blood-fed Ae. aegypti females (76-82%). Houses with ITS had significantly less infected female Ae. aegypti than controls during the peak of the epidemic (OR = 0.15, 95%CI: 0.08-0.29), an effect that was significant up to a year PI (OR = 0.24, 0.15-0.39). Communities strongly accepted the intervention, due to its perceived mode of action, the prevalent risk for Aedes-borne diseases in the area, and the positive feedback from neighbours receiving ITS. CONCLUSIONS/SIGNIFICANCE: We show evidence of the protective efficacy of ITS against an arboviral disease of major relevance, and discuss the relevance of our findings for intervention adoption.


Subject(s)
Aedes/virology , Mosquito Control/methods , Mosquito Nets/statistics & numerical data , Zika Virus Infection/prevention & control , Animals , Chikungunya virus/isolation & purification , Dengue Virus , Female , Housing , Humans , Insect Bites and Stings/prevention & control , Insecticides , Mexico , Mosquito Vectors , Zika Virus/isolation & purification , Zika Virus Infection/epidemiology
9.
Parasit Vectors ; 14(1): 12, 2021 Jan 06.
Article in English | MEDLINE | ID: mdl-33407824

ABSTRACT

BACKGROUND: Aedes albopictus is an indigenous primary vector for dengue and Zika viruses in China. Compared with its insecticide resistance, biology and vector competence, little is known about its genetic variation, which corresponds to environmental variations. Thus, the present study examines how Ae. albopictus varies among different climatic regions in China and deciphers its potential dispersal patterns. METHODS: The genetic variation and population structure of 17 Ae. albopictus populations collected from three climatic regions of China were investigated with 11 microsatellite loci and the mitochondrial coxI gene. RESULTS: Of 44 isolated microsatellite markers, 11 pairs were chosen for genotyping analysis and had an average PIC value of 0.713, representing high polymorphism. The number of alleles was high in each population, with the ne value increasing from the temperate region (3.876) to the tropical region (4.144). Twenty-five coxI haplotypes were detected, and the highest diversity was observed in the tropical region. The mean Ho value (ca. 0.557) of all the regions was significantly lower than the mean He value (ca. 0.684), with nearly all populations significantly departing from HWE and displaying significant population expansion (p value < 0.05). Two genetically isolated groups and three haplotype clades were evaluated via STRUCTURE and haplotype phylogenetic analyses, and the tropical populations were significantly isolated from those in the other regions. Most genetic variation in Ae. albopictus was detected within populations and individuals at 31.40 and 63.04%, respectively, via the AMOVA test, and a relatively significant positive correlation was observed among only the temperate populations via IBD analysis (R2 = 0.6614, p = 0.048). Recent dispersions were observed among different Ae. albopictus populations, and four major migration trends with high gene flow (Nm > 0.4) were reconstructed between the tropical region and the other two regions. Environmental factors, especially temperature and rainfall, may be the leading causes of genetic diversity in different climatic regions. CONCLUSIONS: Continuous dispersion contributes to the genetic communication of Ae. albopictus populations across different climatic regions, and environmental factors, especially temperature and rainfall, may be the leading causes of genetic variation.


Subject(s)
Aedes/genetics , Animal Distribution , Genetics, Population , Aedes/virology , Animals , China/epidemiology , Climate , Dengue/transmission , Electron Transport Complex IV/genetics , Genes, Insect , Genetic Variation , Microsatellite Repeats/genetics , Mosquito Vectors/genetics , Mosquito Vectors/virology , Phylogeny , Polymorphism, Genetic , Zika Virus Infection/transmission
10.
Acta Trop ; 215: 105819, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33406443

ABSTRACT

The outbreaks caused by the Aedes aegypti-transmitted dengue virus (DENV), zakat virus (ZIKV), and chikungunya virus (CHIKV) result in a significant impact to the health systems of tropical countries. Furthermore, the occurrence of patients coinfected by at least two of these arboviruses is an aggravating factor in that scenario. On this basis, surveillance tools such as the Rapid Index Survey for Aedes aegypti (LIRAa) are used to estimate vector infestation in order to improve the prediction of human outbreaks. Ae. aegypti eggs were collected in the city of Vitória da Conquista, in Bahia State, Brazil, and subsequently hatched into larvae, which were analyzed in pools or individually for the presence of DENV, ZIKV, and CHIKV by molecular biology methods. The detection data for arboviruses were crossed with the LIRAa obtained in each region of the study city. Thirty larvae pools were analyzed, and fourteen (46.6%) of them were detected positive for DENV, ZIKV, and/or CHIKV. Among the individually analyzed larvae (n = 30), nine (30%) were positive for any of these arboviruses, and four (13.3%) were simultaneously coinfected by DENV and ZIKV. Furthermore, there was a positive correlation between the detection of circulating arboviruses and LIRAa. The simultaneous Ae. aegypti larvae infection by two different arboviruses is an unprecedented finding. This result suggests the occurrence of a vertical arboviruses co-transmission from the female mosquito to its offspring in nature. The occurrence of concomitant circulation of DENV, ZIKV, and CHIKV in Ae. aegypti from a single study region is another finding of this article. Finally, LIRAa seems to not only estimate vector infestation but also to predict circulation of arboviruses.


Subject(s)
Aedes/virology , Chikungunya virus/isolation & purification , Coinfection/transmission , Dengue Virus/isolation & purification , Infectious Disease Transmission, Vertical , Mosquito Vectors/virology , Zika Virus/isolation & purification , Animals , Female , Humans , Larva/virology
11.
Viruses ; 13(1)2021 Jan 14.
Article in English | MEDLINE | ID: mdl-33466915

ABSTRACT

Mosquito-borne arthropod-borne viruses (arboviruses) such as the dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) are important human pathogens that are responsible for significant global morbidity and mortality. The recent emergence and re-emergence of mosquito-borne viral diseases (MBVDs) highlight the urgent need for safe and effective vaccines, therapeutics, and vector-control approaches to prevent MBVD outbreaks. In nature, arboviruses circulate between vertebrate hosts and arthropod vectors; therefore, disrupting the virus lifecycle in mosquitoes is a major approach for combating MBVDs. Several strategies were proposed to render mosquitoes that are refractory to arboviral infection, for example, those involving the generation of genetically modified mosquitoes or infection with the symbiotic bacterium Wolbachia. Due to the recent development of high-throughput screening methods, an increasing number of drugs with inhibitory effects on mosquito-borne arboviruses in mammalian cells were identified. These antivirals are useful resources that can impede the circulation of arboviruses between arthropods and humans by either rendering viruses more vulnerable in humans or suppressing viral infection by reducing the expression of host factors in mosquitoes. In this review, we summarize recent advances in small-molecule antiarboviral drugs in mammalian and mosquito cells, and discuss how to use these antivirals to block the transmission of MBVDs.


Subject(s)
Aedes/virology , Antiviral Agents/pharmacology , Arbovirus Infections/transmission , Arbovirus Infections/virology , Arboviruses/drug effects , Mosquito Vectors/virology , Aedes/drug effects , Animals , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Arbovirus Infections/drug therapy , Arboviruses/classification , Cells, Cultured , Drug Discovery/methods , Drug Evaluation, Preclinical , Humans , Mosquito Control/methods , Vector Borne Diseases/drug therapy , Vector Borne Diseases/transmission , Vector Borne Diseases/virology , Virus Replication/drug effects
12.
Nat Commun ; 12(1): 151, 2021 01 08.
Article in English | MEDLINE | ID: mdl-33420058

ABSTRACT

Mosquito-borne viruses threaten the Caribbean due to the region's tropical climate and seasonal reception of international tourists. Outbreaks of chikungunya and Zika have demonstrated the rapidity with which these viruses can spread. Concurrently, dengue fever cases have climbed over the past decade. Sustainable disease control measures are urgently needed to quell virus transmission and prevent future outbreaks. Here, to improve upon current control methods, we analyze temporal and spatial patterns of chikungunya, Zika, and dengue outbreaks reported in the Dominican Republic between 2012 and 2018. The viruses that cause these outbreaks are transmitted by Aedes mosquitoes, which are sensitive to seasonal climatological variability. We evaluate whether climate and the spatio-temporal dynamics of dengue outbreaks could explain patterns of emerging disease outbreaks. We find that emerging disease outbreaks were robust to the climatological and spatio-temporal constraints defining seasonal dengue outbreak dynamics, indicating that constant surveillance is required to prevent future health crises.


Subject(s)
Chikungunya Fever/epidemiology , Communicable Diseases, Emerging/epidemiology , Dengue/epidemiology , Disease Outbreaks/statistics & numerical data , Endemic Diseases/statistics & numerical data , Zika Virus Infection/epidemiology , Adolescent , Aedes/virology , Animals , Chikungunya Fever/prevention & control , Chikungunya Fever/transmission , Chikungunya Fever/virology , Chikungunya virus/isolation & purification , Child , Child, Preschool , Communicable Diseases, Emerging/prevention & control , Communicable Diseases, Emerging/transmission , Communicable Diseases, Emerging/virology , Dengue/prevention & control , Dengue/transmission , Dengue/virology , Dengue Virus/isolation & purification , Disease Outbreaks/prevention & control , Dominican Republic/epidemiology , Endemic Diseases/prevention & control , Epidemiological Monitoring , Female , Humans , Infant , Infant, Newborn , Male , Mosquito Control , Mosquito Vectors/virology , Spatio-Temporal Analysis , Young Adult , Zika Virus/isolation & purification , Zika Virus Infection/prevention & control , Zika Virus Infection/transmission , Zika Virus Infection/virology
13.
Parasit Vectors ; 14(1): 76, 2021 Jan 22.
Article in English | MEDLINE | ID: mdl-33482887

ABSTRACT

BACKGROUND: On 11 March 2020, the World Health Organisation (WHO) declared the coronavirus disease 2019 (COVID-19) outbreak to be a pandemic. As the mosquito season progressed, the understandable concern that mosquitoes could transmit the virus began to increase among the general public and public health organisations. We have investigated the vector competence of Culex pipiens and Aedes albopictus, the two most common species of vector mosquitoes in Europe, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the very unusual feeding behaviour of Ae. albopictus, we also evaluated the role of this mosquito in a potential mechanical transmission of the virus. METHODS: For the vector competence study, mosquitoes were allowed to take several infectious blood meals. The mosquitoes were then collected and analysed at 0, 3, 7 and 10 days post-feeding. For the mechanical transmission test, Ae. albopictus females were allowed to feed for a short time on a feeder containing infectious blood and then on a feeder containing virus-free blood. Both mosquitoes and blood were tested for viral presence. RESULTS: Culex pipiens and Ae. albopictus were found not be competent vectors for SARS-CoV-2, and Ae. albopictus was unable to mechanically transmit the virus. CONCLUSIONS: This is the first study to show that the most common species of vector mosquitoes in Europe do not transmit SARS-CoV-2 and that Ae. albopictus is unable to mechanically transmit the virus from a positive host to a healthy host through host-feeding.


Subject(s)
Aedes/virology , Culex/virology , Mosquito Vectors/virology , /physiology , Animals , Blood/virology , Europe , Female , RNA, Viral/analysis , RNA, Viral/isolation & purification , Real-Time Polymerase Chain Reaction , Sheep/blood
14.
J Virol ; 95(6)2021 02 24.
Article in English | MEDLINE | ID: mdl-33328311

ABSTRACT

Zika virus (ZIKV; Flaviviridae, Flavivirus) is an arthropod-borne infection that can result in severe outcomes, particularly in fetuses infected in utero It has been assumed that infection by ZIKV, as well as other viruses, is largely initiated by individual virus particles binding to and entering a cell. However, recent studies have demonstrated that multiple virus particles are frequently delivered to a cell simultaneously and that this collective particle delivery enhances infection. ZIKV is maintained in nature between Aedes aegypti mosquitos and vertebrate hosts, including humans. Human infection is initiated through the injection of a relatively small initial inoculum comprised of a genetically complex virus population. Since most mutations decrease virus fitness, collective particle transmission could benefit ZIKV and other arthropod-borne diseases by facilitating the maintenance of genetic complexity and adaptability during infection or through other mechanisms. Therefore, we utilized a barcoded ZIKV to quantify the number of virus genomes that initiate a plaque. We found that individual plaques contain a mean of 10 infecting viral genomes (range, 1 to 212). Few plaques contained more than two dominant genomes. To determine whether multigenome infectious units consist of collectively transmitting virions, infectious units of ZIKV were then separated mechanically by centrifugation, and heavier fractions were found to contain more genomes per plaque-forming unit, with larger diameters. Finally, larger/heavier infectious units reformed after removal. These data suggest that ZIKV populations consist of a variety of infectious unit sizes, likely mostly made up of aggregates, and only rarely begin with a single virus genome.IMPORTANCE The arthropod-borne Zika virus (ZIKV) infects humans and can cause severe neurological sequelae, particularly in fetuses infected in utero How this virus has been able to spread across vast geological ranges and evolve in new host populations is not yet understood. This research demonstrates a novel mechanism of ZIKV transmission through multigenome aggregates, providing insight into ZIKV evolution, immunologic evasion, and better future therapeutic design. This study shows that ZIKV plaques result from collections of genomes rather than individual genomes, increasing the potential for interactions between ZIKV genotypes.


Subject(s)
Genome, Viral/genetics , Polymorphism, Genetic , Zika Virus Infection/virology , Zika Virus/genetics , Aedes/virology , Animals , Cell Line , DNA Copy Number Variations , Genome Size , Genotype , Humans , Mosquito Vectors/virology , Temperature , Virion/metabolism , Virus Replication , Zika Virus/growth & development , Zika Virus Infection/transmission
15.
PLoS Pathog ; 16(12): e1009134, 2020 12.
Article in English | MEDLINE | ID: mdl-33351855

ABSTRACT

Mosquitoes are responsible for the transmission of many clinically important arboviruses that cause significant levels of annual mortality and socioeconomic health burden worldwide. Deciphering the mechanisms by which mosquitoes modulate arbovirus infection is crucial to understand how viral-host interactions promote vector transmission and human disease. SUMOylation is a post-translational modification that leads to the covalent attachment of the Small Ubiquitin-like MOdifier (SUMO) protein to host factors, which in turn can modulate their stability, interaction networks, sub-cellular localisation, and biochemical function. While the SUMOylation pathway is known to play a key role in the regulation of host immune defences to virus infection in humans, the importance of this pathway during arbovirus infection in mosquito vectors, such as Aedes aegypti (Ae. aegypti), remains unknown. Here we characterise the sequence, structure, biochemical properties, and tissue-specific expression profiles of component proteins of the Ae. aegypti SUMOylation pathway. We demonstrate significant biochemical differences between Ae. aegypti and Homo sapiens SUMOylation pathways and identify cell-type specific patterns of SUMO expression in Ae. aegypti tissues known to support arbovirus replication. Importantly, depletion of core SUMOylation effector proteins (SUMO, Ubc9 and PIAS) in Ae. aegypti cells led to enhanced levels of arbovirus replication from three different families; Zika (Flaviviridae), Semliki Forest (Togaviridae), and Bunyamwera (Bunyaviridae) viruses. Our findings identify an important role for mosquito SUMOylation in the cellular restriction of arboviruses that may directly influence vector competence and transmission of clinically important arboviruses.


Subject(s)
Aedes/virology , Arboviruses/physiology , Host-Pathogen Interactions/physiology , Mosquito Vectors/virology , Virus Replication/physiology , Animals , Arbovirus Infections/transmission , Humans , Sumoylation
16.
PLoS Pathog ; 16(12): e1009068, 2020 12.
Article in English | MEDLINE | ID: mdl-33382858

ABSTRACT

Originating from African forests, Zika virus (ZIKV) has now emerged worldwide in urbanized areas, mainly transmitted by Aedes aegypti mosquitoes. Although Aedes albopictus can transmit ZIKV experimentally and was suspected to be a ZIKV vector in Central Africa, the potential of this species to sustain virus transmission was yet to be uncovered until the end of 2019, when several autochthonous transmissions of the virus vectored by Ae. albopictus occurred in France. Aside from these few locally acquired ZIKV infections, most territories colonized by Ae. albopictus have been spared so far. The risk level of ZIKV emergence in these areas remains however an open question. To assess Ae. albopictus' vector potential for ZIKV and identify key virus outbreak predictors, we built a complete framework using the complementary combination of (i) dose-dependent experimental Ae. albopictus exposure to ZIKV followed by time-dependent assessment of infection and systemic infection rates, (ii) modeling of intra-human ZIKV viremia dynamics, and (iii) in silico epidemiological simulations using an Agent-Based Model. The highest risk of transmission occurred during the pre-symptomatic stage of the disease, at the peak of viremia. At this dose, mosquito infection probability was estimated to be 20%, and 21 days were required to reach the median systemic infection rates. Mosquito population origin, either temperate or tropical, had no impact on infection rates or intra-host virus dynamic. Despite these unfavorable characteristics for transmission, Ae. albopictus was still able to trigger and yield large outbreaks in a simulated environment in the presence of sufficiently high mosquito biting rates. Our results reveal a low but existing epidemic potential of Ae. albopictus for ZIKV, that might explain the absence of large scale ZIKV epidemics so far in territories occupied only by Ae. albopictus. They nevertheless support active surveillance and eradication programs in these territories to maintain the risk of emergence to a low level.


Subject(s)
Mosquito Vectors/metabolism , Mosquito Vectors/virology , Zika Virus Infection/transmission , Aedes/metabolism , Aedes/virology , Animals , Disease Outbreaks , Disease Vectors , Epidemics , Humans , Models, Theoretical , Saliva/virology , Viral Load , Viremia/transmission , Zika Virus/pathogenicity , Zika Virus Infection/epidemiology , Zika Virus Infection/virology
17.
PLoS Negl Trop Dis ; 14(12): e0008971, 2020 12.
Article in English | MEDLINE | ID: mdl-33338046

ABSTRACT

Aedes aegypti is a vector of dengue, chikungunya, and Zika viruses. Current vector control strategies such as community engagement, source reduction, and insecticides have not been sufficient to prevent viral outbreaks. Thus, interest in novel strategies involving genetic engineering is growing. Female mosquitoes rely on flight to mate with males and obtain a bloodmeal from a host. We hypothesized that knockout of genes specifically expressed in female mosquitoes associated with the indirect flight muscles would result in a flightless female mosquito. Using CRISPR-Cas9 we generated loss-of-function mutations in several genes hypothesized to control flight in mosquitoes, including actin (AeAct-4) and myosin (myo-fem) genes expressed specifically in the female flight muscle. Genetic knockout of these genes resulted in 100% flightless females, with homozygous males able to fly, mate, and produce offspring, albeit at a reduced rate when compared to wild type males. Interestingly, we found that while AeAct-4 was haplosufficient, with most heterozygous individuals capable of flight, this was not the case for myo-fem, where about half of individuals carrying only one intact copy could not fly. These findings lay the groundwork for developing novel mechanisms of controlling Ae. aegypti populations, and our results suggest that this mechanism could be applicable to other vector species of mosquito.


Subject(s)
Aedes/genetics , CRISPR-Cas Systems , Insecticides/pharmacology , Mosquito Control , Mosquito Vectors/genetics , Zika Virus Infection/prevention & control , Zika Virus/physiology , Aedes/physiology , Aedes/virology , Animals , Female , Flight, Animal , Gene Knockout Techniques , Humans , Male , Mosquito Vectors/physiology , Mosquito Vectors/virology , Phenotype , Zika Virus Infection/transmission , Zika Virus Infection/virology
18.
BMC Med ; 18(1): 399, 2020 12 17.
Article in English | MEDLINE | ID: mdl-33327961

ABSTRACT

BACKGROUND: Zika 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. METHODS: We 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. RESULTS: We 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). CONCLUSION: Our 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.


Subject(s)
Geographic Mapping , Zika Virus Infection/epidemiology , Aedes/physiology , Aedes/virology , Animals , Disease Outbreaks/history , Ecology , Epidemics , Geography , History, 21st Century , Humans , Travel/statistics & numerical data , Zika Virus/physiology , Zika Virus Infection/history
19.
PLoS Negl Trop Dis ; 14(12): e0008986, 2020 12.
Article in English | MEDLINE | ID: mdl-33370301

ABSTRACT

Japanese encephalitis virus (JEV) is maintained in an enzootic cycle between swine, water birds, and mosquitoes. JEV has circulated indigenously in Asia, with Culex tritaeniorhynchus as the primary vector. In some areas where the primary vector is scarce or absent, sporadic cases of Japanese encephalitis have been reported, with Aedes japonicus japonicus presumed to have the potential as a secondary vector. As one of the world's most invasive culicid species, Ae. j. japonicus carries a considerable health risk for spreading diseases to wider areas, including Europe and North America. Thus, evaluation of its competency as a JEV vector, particularly in a native population, will be essential in preventing potential disease spread. In this study, the two mosquito species' vector competence in transmitting three JEV genotypes (I, III, and V) was assessed, with Cx. tritaeniorhynchus serving as a point of reference. The mosquitoes were virus-fed and the infection rate (IR), dissemination rate (DR), and transmission rate (TR) evaluated individually by either RT-qPCR or focus forming assay. Results showed striking differences between the two species, with IR of 95% (261/274) and 9% (16/177) in Cx. tritaeniorhynchus and Ae. j. japonicus, respectively. Both mosquitoes were susceptible to all three JEV genotypes with significant differences in IR and mean viral titer. Results confirm the primary vector's competence, but the fact that JEV was able to establish in Ae. j. japonicus is of public health significance, and with 2%-16% transmission rate it has the potential to successfully transmit JEV to the next host. This may explain the human cases and infrequent detection in primary vector-free areas. Importantly, Ae. j. japonicus could be a relevant vector spreading the disease into new areas, indicating the need for security measures in areas where the mosquito is distributed or where it may be introduced.


Subject(s)
Aedes/virology , Culex/virology , Encephalitis Virus, Japanese/growth & development , Encephalitis Virus, Japanese/isolation & purification , Encephalitis, Japanese/transmission , Mosquito Vectors/virology , Animals , Asia/epidemiology , Cell Line , Chlorocebus aethiops , Encephalitis Virus, Japanese/genetics , Encephalitis, Japanese/epidemiology , Genotype , Humans , Vero Cells , Viral Envelope Proteins/genetics
20.
PLoS Negl Trop Dis ; 14(12): e0008867, 2020 12.
Article in English | MEDLINE | ID: mdl-33382725

ABSTRACT

BACKGROUND: Aedes aegypti mosquito-borne viruses including Zika (ZIKV), dengue (DENV), yellow fever (YFV), and chikungunya (CHIKV) have emerged and re-emerged globally, resulting in an elevated burden of human disease. Aedes aegypti is found worldwide in tropical, sub-tropical, and temperate areas. The characterization of mosquito blood meals is essential to understand the transmission dynamics of mosquito-vectored pathogens. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report Ae. aegypti and Culex quinquefasciatus host feeding patterns and arbovirus transmission in Northern Mexico using a metabarcoding-like approach with next-generation deep sequencing technology. A total of 145 Ae. aegypti yielded a blood meal analysis result with 107 (73.8%) for a single vertebrate species and 38 (26.2%) for two or more. Among the single host blood meals for Ae. aegypti, 28.0% were from humans, 54.2% from dogs, 16.8% from cats, and 1.0% from tortoises. Among those with more than one species present, 65.9% were from humans and dogs. For Cx. quinquefasciatus, 388 individuals yielded information with 326 (84%) being from a single host and 63 (16.2%) being from two or more hosts. Of the single species blood meals, 77.9% were from dogs, 6.1% from chickens, 3.1% from house sparrows, 2.4% from humans, while the remaining 10.5% derived from other 12 host species. Among those which had fed on more than one species, 11% were from dogs and humans, and 89% of other host species combinations. Forage ratio analysis revealed dog as the most over-utilized host by Ae. aegypti (= 4.3) and Cx. quinquefasciatus (= 5.6) and the human blood index at 39% and 4%, respectively. A total of 2,941 host-seeking female Ae. aegypti and 3,536 Cx. quinquefasciatus mosquitoes were collected in the surveyed area. Of these, 118 Ae. aegypti pools and 37 Cx. quinquefasciatus pools were screened for seven arboviruses (ZIKV, DENV 1-4, CHIKV, and West Nile virus (WNV)) using qRT-PCR and none were positive (point prevalence = 0%). The 95%-exact upper limit confidence interval was 0.07% and 0.17% for Ae. aegypti and Cx. quinquefasciatus, respectively. CONCLUSIONS/SIGNIFICANCE: The low human blood feeding rate in Ae. aegypti, high rate of feeding on mammals by Cx. quinquefasciatus, and the potential risk to transmission dynamics of arboviruses in highly urbanized areas of Northern Mexico is discussed.


Subject(s)
Aedes/virology , Arbovirus Infections/veterinary , Arboviruses/physiology , Culex/virology , Vertebrates/virology , Animals , Arbovirus Infections/blood , Arbovirus Infections/transmission , DNA Barcoding, Taxonomic , Feeding Behavior , High-Throughput Nucleotide Sequencing , Host-Pathogen Interactions , Models, Biological , Mosquito Vectors/virology , Species Specificity , Vertebrates/blood
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