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1.
Nat Commun ; 12(1): 2290, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33863888

RESUMO

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.


Assuntos
Antivirais/administração & dosagem , Vírus Defeituosos/genética , Mosquitos Vetores/efeitos dos fármacos , Infecção por Zika virus/tratamento farmacológico , Zika virus/genética , Aedes/efeitos dos fármacos , Aedes/virologia , Animais , Chlorocebus aethiops , Biologia Computacional , Evolução Molecular Direcionada , Modelos Animais de Doenças , Feminino , Aptidão Genética , Genoma Viral/genética , Células HEK293 , Humanos , Camundongos , Controle de Mosquitos/métodos , Mosquitos Vetores/virologia , Fases de Leitura Aberta/genética , RNA Viral/genética , Células Vero , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia
2.
PLoS Negl Trop Dis ; 15(3): e0009259, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33705409

RESUMO

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.


Assuntos
Febre de Chikungunya/epidemiologia , Dengue/epidemiologia , Infecção por Zika virus/epidemiologia , Aedes/fisiologia , Aedes/virologia , Animais , Febre de Chikungunya/economia , Febre de Chikungunya/virologia , Vírus Chikungunya/fisiologia , Clima , Colômbia/epidemiologia , Dengue/economia , Dengue/virologia , Vírus da Dengue/fisiologia , Ecossistema , Humanos , Mosquitos Vetores/fisiologia , Mosquitos Vetores/virologia , América do Sul , Temperatura , Zika virus/fisiologia , Infecção por Zika virus/economia , Infecção por Zika virus/virologia
3.
Nat Commun ; 12(1): 1810, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33753725

RESUMO

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.


Assuntos
Algoritmos , Vírus da Dengue/genética , Dengue/transmissão , Modelos Teóricos , Adulto , Aedes/virologia , Animais , Criança , Dengue/epidemiologia , Dengue/virologia , Vírus da Dengue/classificação , Vírus da Dengue/fisiologia , Genoma Viral/genética , Interações Hospedeiro-Patógeno , Humanos , Mosquitos Vetores/virologia , Filogenia , Filogeografia/métodos , Filogeografia/estatística & dados numéricos , Dinâmica Populacional , Tailândia/epidemiologia
4.
Nat Commun ; 12(1): 1671, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33723237

RESUMO

Zika virus (ZIKV) has caused large, brief outbreaks in isolated populations, however ZIKV can also persist at low levels over multiple years. The reasons for these diverse transmission dynamics remain poorly understood. In Fiji, which has experienced multiple large single-season dengue epidemics, there was evidence of multi-year transmission of ZIKV between 2013 and 2017. To identify factors that could explain these differences in dynamics between closely related mosquito-borne flaviviruses, we jointly fit a transmission dynamic model to surveillance, serological and molecular data. We estimate that the observed dynamics of ZIKV were the result of two key factors: strong seasonal effects, which created an ecologically optimal time of year for outbreaks; and introduction of ZIKV after this optimal time, which allowed ZIKV transmission to persist over multiple seasons. The ability to jointly fit to multiple data sources could help identify a similar range of possible outbreak dynamics in other settings.


Assuntos
Infecções por Flavivirus/epidemiologia , Infecções por Flavivirus/transmissão , Animais , Culicidae , Dengue/transmissão , Vírus da Dengue , Surtos de Doenças , Epidemias , Fiji/epidemiologia , Flavivirus , Humanos , Mosquitos Vetores/virologia , Estações do Ano , Zika virus , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/transmissão
5.
Mem Inst Oswaldo Cruz ; 115: e200313, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33533870

RESUMO

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.


Assuntos
Aedes/efeitos dos fármacos , Insetos Vetores/genética , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Mosquitos Vetores/efeitos dos fármacos , Piretrinas/farmacologia , Aedes/genética , Aedes/virologia , Animais , Guiana Francesa , Insetos Vetores/efeitos dos fármacos , Controle de Mosquitos/métodos , Mosquitos Vetores/virologia , Análise Espaço-Temporal
6.
Parasit Vectors ; 14(1): 12, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407824

RESUMO

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.


Assuntos
Aedes/genética , Distribuição Animal , Genética Populacional , Aedes/virologia , Animais , China/epidemiologia , Clima , Dengue/transmissão , Complexo IV da Cadeia de Transporte de Elétrons/genética , Genes de Insetos , Variação Genética , Repetições de Microssatélites/genética , Mosquitos Vetores/genética , Mosquitos Vetores/virologia , Filogenia , Polimorfismo Genético , Infecção por Zika virus/transmissão
7.
Acta Trop ; 215: 105819, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33406443

RESUMO

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.


Assuntos
Aedes/virologia , Vírus Chikungunya/isolamento & purificação , Coinfecção/transmissão , Vírus da Dengue/isolamento & purificação , Transmissão Vertical de Doença Infecciosa , Mosquitos Vetores/virologia , Zika virus/isolamento & purificação , Animais , Feminino , Humanos , Larva/virologia
8.
Viruses ; 13(1)2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33466915

RESUMO

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.


Assuntos
Aedes/virologia , Antivirais/farmacologia , Infecções por Arbovirus/transmissão , Infecções por Arbovirus/virologia , Arbovirus/efeitos dos fármacos , Mosquitos Vetores/virologia , Aedes/efeitos dos fármacos , Animais , Antivirais/química , Antivirais/uso terapêutico , Infecções por Arbovirus/tratamento farmacológico , Arbovirus/classificação , Células Cultivadas , Descoberta de Drogas/métodos , Avaliação Pré-Clínica de Medicamentos , Humanos , Controle de Mosquitos/métodos , Doenças Transmitidas por Vetores/tratamento farmacológico , Doenças Transmitidas por Vetores/transmissão , Doenças Transmitidas por Vetores/virologia , Replicação Viral/efeitos dos fármacos
9.
Parasit Vectors ; 14(1): 22, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407778

RESUMO

BACKGROUND: Due to an increase in mosquito habitats and the lack facilities to carry out basic mosquito control, construction sites in China are more likely to experience secondary dengue fever infection after importation of an initial infection, which may then increase the number of infections in the neighboring communities and the chance of community transmission. The aim of this study was to investigate how to effectively reduce the transmission of dengue fever at construction sites and the neighboring communities. METHODS: The Susceptible-Exposed-Infectious/Asymptomatic-Recovered (SEIAR) model of human and SEI model of mosquitoes were developed to estimate the transmission of dengue virus between humans and mosquitoes within the construction site and within a neighboring community, as well between each of these. With the calibrated model, we further estimated the effectiveness of different intervention scenarios targeting at reducing the transmissibility at different locations (i.e. construction sites and community) with the total attack rate (TAR) and the duration of the outbreak (DO). RESULTS: A total of 102 construction site-related and 131 community-related cases of dengue fever were reported in our area of study. Without intervention, the number of cases related to the construction site and the community rose to 156 (TAR: 31.25%) and 10,796 (TAR: 21.59%), respectively. When the transmission route from mosquitoes to humans in the community was cut off, the number of community cases decreased to a minimum of 33 compared with other simulated scenarios (TAR: 0.068%, DO: 60 days). If the transmission route from infectious mosquitoes in the community and that from the construction site to susceptible people on the site were cut off at the same time, the number of cases on the construction site dropped to a minimum of 74 (TAR: 14.88%, DO: 66 days). CONCLUSIONS: To control the outbreak of dengue fever effectively on both the construction site and in the community, interventions needed to be made both within the community and from the community to the construction site. If interventions only took place within the construction site, the number of cases on the construction site would not be reduced. Also, interventions implemented only within the construction site or between the construction site and the community would not lead to a reduction in the number of cases in the community.


Assuntos
Dengue/prevenção & controle , Dengue/transmissão , Infecções Assintomáticas/epidemiologia , China/epidemiologia , Controle de Doenças Transmissíveis , Indústria da Construção , Dengue/epidemiologia , Dengue/virologia , Vírus da Dengue/fisiologia , Surtos de Doenças/prevenção & controle , Suscetibilidade a Doenças/epidemiologia , Suscetibilidade a Doenças/virologia , Humanos , Incidência , Modelos Teóricos , Controle de Mosquitos , Mosquitos Vetores/crescimento & desenvolvimento , Mosquitos Vetores/virologia , Características de Residência , Local de Trabalho
10.
Nat Commun ; 12(1): 151, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420058

RESUMO

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.


Assuntos
Febre de Chikungunya/epidemiologia , Doenças Transmissíveis Emergentes/epidemiologia , Dengue/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Doenças Endêmicas/estatística & dados numéricos , Infecção por Zika virus/epidemiologia , Adolescente , Aedes/virologia , Animais , Febre de Chikungunya/prevenção & controle , Febre de Chikungunya/transmissão , Febre de Chikungunya/virologia , Vírus Chikungunya/isolamento & purificação , Criança , Pré-Escolar , Doenças Transmissíveis Emergentes/prevenção & controle , Doenças Transmissíveis Emergentes/transmissão , Doenças Transmissíveis Emergentes/virologia , Dengue/prevenção & controle , Dengue/transmissão , Dengue/virologia , Vírus da Dengue/isolamento & purificação , Surtos de Doenças/prevenção & controle , República Dominicana/epidemiologia , Doenças Endêmicas/prevenção & controle , Monitoramento Epidemiológico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Controle de Mosquitos , Mosquitos Vetores/virologia , Análise Espaço-Temporal , Adulto Jovem , Zika virus/isolamento & purificação , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia
11.
Parasit Vectors ; 14(1): 76, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33482887

RESUMO

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.


Assuntos
Aedes/virologia , Culex/virologia , Mosquitos Vetores/virologia , /fisiologia , Animais , Sangue/virologia , Europa (Continente) , Feminino , RNA Viral/análise , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Ovinos/sangue
12.
J Virol ; 95(6)2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33328311

RESUMO

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.


Assuntos
Genoma Viral/genética , Polimorfismo Genético , Infecção por Zika virus/virologia , Zika virus/genética , Aedes/virologia , Animais , Linhagem Celular , Variações do Número de Cópias de DNA , Tamanho do Genoma , Genótipo , Humanos , Mosquitos Vetores/virologia , Temperatura , Vírion/metabolismo , Replicação Viral , Zika virus/crescimento & desenvolvimento , Infecção por Zika virus/transmissão
13.
PLoS Pathog ; 16(12): e1009134, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33351855

RESUMO

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.


Assuntos
Aedes/virologia , Arbovirus/fisiologia , Interações Hospedeiro-Patógeno/fisiologia , Mosquitos Vetores/virologia , Replicação Viral/fisiologia , Animais , Infecções por Arbovirus/transmissão , Humanos , Sumoilação
14.
PLoS Pathog ; 16(12): e1009068, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33382858

RESUMO

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.


Assuntos
Mosquitos Vetores/metabolismo , Mosquitos Vetores/virologia , Infecção por Zika virus/transmissão , Aedes/metabolismo , Aedes/virologia , Animais , Surtos de Doenças , Vetores de Doenças , Epidemias , Humanos , Modelos Teóricos , Saliva/virologia , Carga Viral , Viremia/transmissão , Zika virus/patogenicidade , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/virologia
15.
PLoS Negl Trop Dis ; 14(12): e0008971, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33338046

RESUMO

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.


Assuntos
Aedes/genética , Sistemas CRISPR-Cas , Inseticidas/farmacologia , Controle de Mosquitos , Mosquitos Vetores/genética , Infecção por Zika virus/prevenção & controle , Zika virus/fisiologia , Aedes/fisiologia , Aedes/virologia , Animais , Feminino , Voo Animal , Técnicas de Inativação de Genes , Humanos , Masculino , Mosquitos Vetores/fisiologia , Mosquitos Vetores/virologia , Fenótipo , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia
16.
Viruses ; 12(12)2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-33327649

RESUMO

A crucial, but unresolved question concerning mosquito-borne virus transmission is how these viruses can remain endemic in regions where the transmission is halted for long periods of time, due to mosquito inactivity in, e.g., winter. In northern Europe, Sindbis virus (SINV) (genus alphavirus, Togaviridae) is transmitted among birds by Culex mosquitoes during the summer, with occasional symptomatic infections occurring in humans. In winter 2018-19, we sampled hibernating Culex spp females in a SINV endemic region in Sweden and assessed them individually for SINV infection status, blood-feeding status, and species. The results showed that 35 out of the 767 collected mosquitoes were infected by SINV, i.e., an infection rate of 4.6%. The vast majority of the collected mosquitoes had not previously blood-fed (98.4%) and were of the species Cx. pipiens (99.5%). This is the first study of SINV overwintering, and it concludes that SINV can be commonly found in the hibernating Cx. pipiens population in an endemic region in Sweden, and that these mosquitoes become infected through other means besides blood-feeding. Further studies on mosquito ecology and viral interactions are needed to elucidate the mechanisms of the persistence of these viruses over winter.


Assuntos
Infecções por Alphavirus/epidemiologia , Infecções por Alphavirus/virologia , Culex/virologia , Mosquitos Vetores/virologia , Vírus Sindbis/fisiologia , Infecções por Alphavirus/transmissão , Animais , Vigilância em Saúde Pública , RNA Viral , Estações do Ano , Suécia/epidemiologia
17.
Viruses ; 12(12)2020 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-33339099

RESUMO

RNA of Kyzylagach virus (KYZV), a Sindbis-like mosquito-borne alphavirus from Western equine encephalitis virus complex, was detected in four pools (out of 221 pools examined), encompassing 10,784 female Culex modestus mosquitoes collected at a fishpond in south Moravia, Czech Republic, with a minimum infection rate of 0.04%. This alphavirus was never detected in Central Europe before.


Assuntos
Infecções por Alphavirus/transmissão , Infecções por Alphavirus/virologia , Culicidae/virologia , Mosquitos Vetores/virologia , Vírus Sindbis , Animais , Europa (Continente)/epidemiologia , Feminino
18.
Viruses ; 12(12)2020 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-33339336

RESUMO

Using molecular techniques and bioinformatics tools, we studied the vector-host interactions and the molecular epidemiology of West Nile virus (WNV) in western Iran. Mosquitoes were collected during 2017 and 2018. DNA typing assays were used to study vector-host interactions. Mosquitoes were screened by RT-PCR for the genomes of five virus families. WNV-positive samples were fully sequenced and evolutionary tree and molecular architecture were constructed by Geneious software and SWISS-MODEL workspace, respectively. A total of 5028 mosquito specimens were collected and identified. The most prevalent species was Culex (Cx.) pipiens complex (57.3%). Analysis of the blood-feeding preferences of blood-fed mosquitoes revealed six mammalian and one bird species as hosts. One mosquito pool containing non-blood-fed Cx. theileri and one blood-fed Culex pipiens pipiens (Cpp.) biotype pipiens were positive for WNV. A phylogram indicated that the obtained WNV sequences belonged to lineage 2, subclade 2 g. Several amino acid substitutions suspected as virulence markers were observed in the Iranian WNV strains. The three-dimensional structural homology model of the E-protein identified hot spot domains known to facilitate virus invasion and neurotropism. The recent detection of WNV lineage 2 in mosquitoes from several regions of Iran in consecutive years suggests that the virus is established in the country.


Assuntos
Vetores de Doenças , Interações Hospedeiro-Patógeno , Febre do Nilo Ocidental/transmissão , Febre do Nilo Ocidental/virologia , Vírus do Nilo Ocidental/fisiologia , Sequência de Aminoácidos , Animais , Evolução Molecular , Genoma Viral , Genômica/métodos , Geografia Médica , Humanos , Irã (Geográfico)/epidemiologia , Mosquitos Vetores/virologia , Filogenia , Dinâmica Populacional , Prevalência , Conformação Proteica , Proteínas Estruturais Virais/química , Proteínas Estruturais Virais/metabolismo , Virulência , Fatores de Virulência , Sequenciamento Completo do Genoma
19.
PLoS Negl Trop Dis ; 14(12): e0008986, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33370301

RESUMO

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.


Assuntos
Aedes/virologia , Culex/virologia , Vírus da Encefalite Japonesa (Espécie)/crescimento & desenvolvimento , Vírus da Encefalite Japonesa (Espécie)/isolamento & purificação , Encefalite Japonesa/transmissão , Mosquitos Vetores/virologia , Animais , Ásia/epidemiologia , Linhagem Celular , Chlorocebus aethiops , Vírus da Encefalite Japonesa (Espécie)/genética , Encefalite Japonesa/epidemiologia , Genótipo , Humanos , Células Vero , Proteínas do Envelope Viral/genética
20.
PLoS Negl Trop Dis ; 14(12): e0008867, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33382725

RESUMO

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.


Assuntos
Aedes/virologia , Infecções por Arbovirus/veterinária , Arbovirus/fisiologia , Culex/virologia , Vertebrados/virologia , Animais , Infecções por Arbovirus/sangue , Infecções por Arbovirus/transmissão , Código de Barras de DNA Taxonômico , Comportamento Alimentar , Sequenciamento de Nucleotídeos em Larga Escala , Interações Hospedeiro-Patógeno , Modelos Biológicos , Mosquitos Vetores/virologia , Especificidade da Espécie , Vertebrados/sangue
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