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1.
Sci Rep ; 12(1): 9536, 2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35681077

RESUMO

Mosquito saliva facilitates blood feeding through the anti-haemostatic, anti-inflammatory and immunomodulatory properties of its proteins. However, the potential contribution of non-coding RNAs to host manipulation is still poorly understood. We analysed small RNAs from Aedes aegypti saliva and salivary glands and show here that chikungunya virus-infection triggers both the siRNA and piRNA antiviral pathways with limited effects on miRNA expression profiles. Saliva appears enriched in specific miRNA subsets and its miRNA content is well conserved among mosquitoes and ticks, clearly pointing to a non-random sorting and occurrence. Finally, we provide evidence that miRNAs from Ae. aegypti saliva may target human immune and inflammatory pathways, as indicated by prediction analysis and searching for experimentally validated targets of identical human miRNAs. Overall, we believe these observations convincingly support a scenario where both proteins and miRNAs from mosquito saliva are injected into vertebrates during blood feeding and contribute to the complex vector-host-pathogen interactions.


Assuntos
Aedes , Vírus Chikungunya , MicroRNAs , Aedes/genética , Aedes/virologia , Animais , Febre de Chikungunya , Humanos , MicroRNAs/genética , Mosquitos Vetores/genética , Mosquitos Vetores/virologia , RNA Interferente Pequeno/genética , Saliva , Glândulas Salivares/metabolismo
2.
Proc Natl Acad Sci U S A ; 119(24): e2114309119, 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35675424

RESUMO

Viruses transmitted by Aedes mosquitoes are an increasingly important global cause of disease. Defining common determinants of host susceptibility to this large group of heterogenous pathogens is key for informing the rational design of panviral medicines. Infection of the vertebrate host with these viruses is enhanced by mosquito saliva, a complex mixture of salivary-gland-derived factors and microbiota. We show that the enhancement of infection by saliva was dependent on vascular function and was independent of most antisaliva immune responses, including salivary microbiota. Instead, the Aedes gene product sialokinin mediated the enhancement of virus infection through a rapid reduction in endothelial barrier integrity. Sialokinin is unique within the insect world as having a vertebrate-like tachykinin sequence and is absent from Anopheles mosquitoes, which are incompetent for most arthropod-borne viruses, whose saliva was not proviral and did not induce similar vascular permeability. Therapeutic strategies targeting sialokinin have the potential to limit disease severity following infection with Aedes-mosquito-borne viruses.


Assuntos
Aedes , Infecções por Arbovirus , Arbovírus , Saliva , Taquicininas , Viroses , Aedes/genética , Aedes/virologia , Animais , Infecções por Arbovirus/transmissão , Arbovírus/genética , Arbovírus/metabolismo , Saliva/virologia , Taquicininas/genética , Taquicininas/metabolismo , Viroses/transmissão
3.
Commun Biol ; 5(1): 607, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35725909

RESUMO

The N6-methyladenosine (m6A) modification of RNA has been reported to affect viral infections. Studies have confirmed the role of m6A in replication of several vector-borne flaviviruses, including dengue virus (DENV), in mammalian cells. Here, we explored the role of m6A in DENV replication in the mosquito Aedes aegypti Aag2 cell line. We first determined the presence of m6A on the RNAs from mosquito cells and using methylated RNA immunoprecipitation and sequencing (MeRIP-Seq) identified m6A modification of the mosquito transcriptome and those that changed upon DENV infection. Depletion of m6A methyltransferases and the m6A binding protein YTHDF3 RNAs decreased the replication of DENV. In particular, we found that the Ae. aegypti ubiquitin carrier protein 9 (Ubc9) is m6A modified and its expression increases after DENV infection. Silencing of the gene and ectopic expression of Ubc9 led to reduced and increased DENV replication, respectively. The abundance of Ubc9 mRNA and its stability were reduced with the inhibition of m6A modification, implying that m6A modification of Ubc9 might enhance expression of the gene. We also show that the genome of DENV is m6A modified at five sites in mosquito cells. Altogether, this work reveals the involvement of m6A modification in Ae. aegypti-DENV interaction.


Assuntos
Adenosina , Aedes , Vírus da Dengue , Transcriptoma , Adenosina/análogos & derivados , Aedes/genética , Aedes/virologia , Animais , Linhagem Celular , Vírus da Dengue/fisiologia , RNA/genética , Replicação Viral
4.
Parasit Vectors ; 15(1): 233, 2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35761349

RESUMO

BACKGROUND: Fatty acids are the building blocks of complex lipids essential for living organisms. In mosquitoes, fatty acids are involved in cell membrane production, energy conservation and expenditure, innate immunity, development and reproduction. Fatty acids are synthesized by a multifunctional enzyme complex called fatty acid synthase (FAS). Several paralogues of FAS were found in the Aedes aegypti mosquito. However, the molecular characteristics and expression of some of these paralogues have not been investigated. METHODS: Genome assemblies of Ae. aegypti were analyzed, and orthologues of human FAS was identified. Phylogenetic analysis and in silico molecular characterization were performed to identify the functional domains of the Ae. aegypti FAS (AaFAS). Quantitative analysis and loss-of-function experiments were performed to determine the significance of different AaFAS transcripts in various stages of development, expression following different diets and the impact of AaFAS on dengue virus, serotype 2 (DENV2) infection and transmission. RESULTS: We identified seven putative FAS genes in the Ae. aegypti genome assembly, based on nucleotide similarity to the FAS proteins (tBLASTn) of humans, other mosquitoes and invertebrates. Bioinformatics and molecular analyses suggested that only five of the AaFAS genes produce mRNA and therefore represent complete gene models. Expression levels of AaFAS varied among developmental stages and between male and female Ae. aegypti. Quantitative analyses revealed that expression of AaFAS1, the putative orthologue of the human FAS, was highest in adult females. Transient knockdown (KD) of AaFAS1 did not induce a complete compensation by other AaFAS genes but limited DENV2 infection of Aag2 cells in culture and the midgut of the mosquito. CONCLUSION: AaFAS1 is the predominant AaFAS in adult mosquitoes. It has the highest amino acid similarity to human FAS and contains all enzymatic domains typical of human FAS. AaFAS1 also facilitated DENV2 replication in both cell culture and in mosquito midguts. Our data suggest that AaFAS1 may play a role in transmission of dengue viruses and could represent a target for intervention strategies.


Assuntos
Aedes , Infecções por Arbovirus , Dengue , Ácido Graxo Sintases , Aedes/genética , Aedes/virologia , Animais , Vírus da Dengue , Ácido Graxo Sintases/genética , Ácidos Graxos , Feminino , Humanos , Proteínas de Insetos/genética , Masculino , Mosquitos Vetores/virologia , Filogenia , Replicação Viral
5.
Goiânia; SES-GO; 27 maio 2022. 1-6 p.
Não convencional em Português | Coleciona SUS, Coleciona SUS, CONASS, SES-GO | ID: biblio-1371259

RESUMO

Considerada uma arbovirose urbana, a dengue é uma doença febril provocada por quatro tipos de vírus (DENV1, DENV2, DENV3 e DENV4) e transmitida principalmente pelo mosquito Aedes aegypti (BRASIL, 2021a). Cerca de 400 milhões de pessoas no mundo são infectadas pelo vírus da dengue e aproximadamente 40.000 óbitos ocorrem devido à doença a cada ano (CDC, 2021a). Embora tenha ocorrido uma redução dos números de casos de dengue no Estado de Goiás de 168.737 casos no ano em 2014 para 57.715 casos em 2021 (BRASIL, 2021b), análise de situação da dengue desenvolvida pela Secretaria de Estado de Saúde de Goiás (SES/GO), apontou que o Estado de Goiás se manteve, neste período, entre as dez piores Unidades Federativas (UF) brasileiras quando o assunto é a alta taxa de incidência de dengue. O método de controle vetorial praticado na esfera estadual tem sido o recomendado pelas Diretrizes Nacionais para a Prevenção e Controle de Epidemias de Dengue. No entanto, as ações não têm reduzido significativamente a taxa de incidência da doença, uma vez que a média de declínio dos últimos três biênios (2019/2020; 2020/2021; 2021/2022) tem sido de apenas 5,6%. Considerando o cenário levantado, esta síntese tem o objetivo de identificar estratégias exitosas de controle de longa permanência da dengue e do vetor Aedes aegypti implantadas ou estudadas no Brasil e no mundo.


Considered an urban arbovirus, dengue is a febrile disease caused by four types of viruses (DENV1, DENV2, DENV3 and DENV4) and transmitted mainly by the Aedes aegypti mosquito (BRASIL, 2021a). About 400 million people worldwide are infected with the dengue virus and approximately 40,000 deaths occur from the disease each year (CDC, 2021a). Although there has been a reduction in the number of dengue cases in the State of Goiás from 168,737 cases in the year in 2014 to 57,715 cases in 2021 (BRASIL, 2021b), an analysis of the dengue situation developed by the Goiás State Health Department (SES/ GO), pointed out that the State of Goiás remained, in this period, among the ten worst Brazilian Federative Units (FU) when it comes to the high incidence rate of dengue. The vector control method practiced at the state level has been recommended by the National Guidelines for the Prevention and Control of Dengue Epidemics. However, actions have not significantly reduced the disease incidence rate, since the average decline in the last three biennia (2019/2020; 2020/2021; 2021/2022) has been only 5.6%. Considering the scenario raised, this synthesis aims to identify successful strategies for the long-term control of dengue and the Aedes aegypti vector implanted or studied in Brazil and in the world.


Assuntos
Aedes/virologia , Controle de Vetores , Aedes/genética , Introgressão Genética
6.
Virology ; 570: 67-80, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35390695

RESUMO

Septins are a family of GTP-binding proteins identified in insects and mammals. Septins are components of the cytoskeleton and participate in cytokinesis, chromosomal segregation, intracellular vesicular traffic, and response to pathogens. Human septin 6 was identified as necessary for hepatitis C virus replication. Information about host factors necessary for flavivirus replication in mosquitoes is scarce. Thus, the role of septins in the replicative cycle of dengue virus in Aedes spp. derived cells was investigated. Through bioinformatic analysis, sequences of septin-like proteins were identified. Infected mosquito cells showed increased expression of Sep2. Colocalization analysis, proximity ligation and immunoprecipitation assays indicated that Sep2 interacts with proteins E, NS3 and NS5, but not NS1. Immunoelectron microscopy evidenced the presence of AalSep2 in replicative complexes. Finally, silencing of Sep2 expression resulted in a significant decrease in virus progeny, indicating that Sep2 is a host factor participating in dengue virus replication in mosquito cells.


Assuntos
Aedes , Dengue , Flavivirus , Replicação Viral , Aedes/virologia , Animais , Dengue/virologia , Flavivirus/metabolismo , Flavivirus/fisiologia , Humanos , Mamíferos , Septinas/genética , Septinas/metabolismo
7.
J Virol ; 96(10): e0016522, 2022 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-35467365

RESUMO

Zika virus is a mosquito-borne flavivirus known to cause severe birth defects and neuroimmunological disorders. We have previously demonstrated that mosquito transmission of Zika virus decreases with temperature. While transmission was optimized at 29°C, it was limited at cool temperatures (<22°C) due to poor virus establishment in the mosquitoes. Temperature is one of the strongest drivers of vector-borne disease transmission due to its profound effect on ectothermic mosquito vectors, viruses, and their interaction. Although there is substantial evidence of temperature effects on arbovirus replication and dissemination inside mosquitoes, little is known about whether temperature affects virus replication directly or indirectly through mosquito physiology. In order to determine the mechanisms behind temperature-induced changes in Zika virus transmission potential, we investigated different steps of the virus replication cycle in mosquito cells (C6/36) at optimal (28°C) and cool (20°C) temperatures. We found that the cool temperature did not alter Zika virus entry or translation, but it affected genome replication and reduced the amount of double-stranded RNA replication intermediates. If replication complexes were first formed at 28°C and the cells were subsequently shifted to 20°C, the late steps in the virus replication cycle were efficiently completed. These data suggest that cool temperature decreases the efficiency of Zika virus genome replication in mosquito cells. This phenotype was observed in the Asian lineage of Zika virus, while the African lineage Zika virus was less restricted at 20°C. IMPORTANCE With half of the human population at risk, arboviral diseases represent a substantial global health burden. Zika virus, previously known to cause sporadic infections in humans, emerged in the Americas in 2015 and quickly spread worldwide. There was an urgent need to better understand the disease pathogenesis and develop therapeutics and vaccines, as well as to understand, predict, and control virus transmission. In order to efficiently predict the seasonality and geography for Zika virus transmission, we need a deeper understanding of the host-pathogen interactions and how they can be altered by environmental factors such as temperature. Identifying the step in the virus replication cycle that is inhibited under cool conditions can have implications in modeling the temperature suitability for arbovirus transmission as global environmental patterns change. Understanding the link between pathogen replication and environmental conditions can potentially be exploited to develop new vector control strategies in the future.


Assuntos
Aedes , Temperatura , Replicação Viral , Zika virus , Aedes/virologia , Animais , Mosquitos Vetores/virologia , Zika virus/fisiologia
8.
Ecohealth ; 19(1): 75-84, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35318521

RESUMO

Dengue virus (DENV) 1-4 is the etiological agent of dengue, the most important viral infection transmitted by Aedes spp mosquitoes to humans. Our goal was to identify the circulating DENV in Aedes aegypti collected in an area of Brazil where all four DENV serotypes had already been detected in humans, understand the epidemiology better, and to test the vector as a virological surveillance tool. Twenty-eight larvae pools and 174 females of Aedes aegypti were screened by reverse transcriptase quantitative polymerase chain reaction and semi-nested PCR assays. PCR products were sequenced, and phylogenetic analyses were performed. Nine larvae pools (32.1%) were positive for DENV, four (44.4%) with DENV-3, and five (55.6%) with more than one serotype. Fifteen females (8.6%) were positive for any DENV serotype. DENV-1 isolates belong to genotype V, DENV-2 to American-Asian genotype, DENV-3 to genotypes I and III, and DENV-4 to genotypes I and II. We demonstrate for the first time the co-circulation of all four DENV serotypes in larvae pools and adult Aedes aegypti in a hyperendemic area. This scenario represents a challenge for disease control and reinforces the importance of virological surveillance in the vector as a tool for predicting circulating DENV serotypes in humans.


Assuntos
Aedes , Vírus da Dengue , Dengue , Aedes/virologia , Animais , Brasil , Dengue/epidemiologia , Vírus da Dengue/genética , Feminino , Larva , Mosquitos Vetores/virologia , Filogenia , Sorogrupo
9.
Molecules ; 27(3)2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35163978

RESUMO

Light-based events in insects deserve increasing attention for various reasons. Besides their roles in inter- and intra-specific visual communication, with biological, ecological and taxonomical implications, optical properties are also promising tools for the monitoring of insect pests and disease vectors. Among these is the Asian tiger mosquito, Aedes albopictus, a global arbovirus vector. Here we have focused on the autofluorescence characterization of Ae. albopictus adults using a combined imaging and spectrofluorometric approach. Imaging has evidenced that autofluorescence rises from specific body compartments, such as the head appendages, and the abdominal and leg scales. Spectrofluorometry has demonstrated that emission consists of a main band in the 410-600 nm region. The changes in the maximum peak position, between 430 nm and 500 nm, and in the spectral width, dependent on the target structure, indicate the presence, at variable degrees, of different fluorophores, likely resilin, chitin and melanins. The aim of this work has been to provide initial evidence on the so far largely unexplored autofluorescence of Ae. albopictus, to furnish new perspectives for the set-up of species- and sex-specific investigation of biological functions as well as of strategies for in-flight direct detection and surveillance of mosquito vectors.


Assuntos
Aedes/metabolismo , Medições Luminescentes/métodos , Proteínas Luminescentes/metabolismo , Aedes/virologia , Animais , Arbovírus , Feminino , Proteínas Luminescentes/análise , Masculino , Mosquitos Vetores
10.
Viruses ; 14(2)2022 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-35215949

RESUMO

Mosquito-borne viruses (MBVs), also known as moboviruses, are associated mainly with mosquitoes and are able to infect humans and other vertebrates [...].


Assuntos
Ecologia , Mosquitos Vetores/virologia , Aedes/fisiologia , Aedes/virologia , Animais , Infecções por Arbovirus/prevenção & controle , Infecções por Arbovirus/transmissão , Infecções por Arbovirus/virologia , Arbovírus/fisiologia , Humanos , Mosquitos Vetores/fisiologia
11.
Toxins (Basel) ; 14(2)2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-35202174

RESUMO

Mosquito densoviruses (MDVs) are mosquito-specific viruses that are recommended as mosquito bio-control agents. The MDV Aedes aegypti densovirus (AeDNV) is a good candidate for controlling mosquitoes. However, the slow activity restricts their widespread use for vector control. In this study, we introduced the Bacillus thuringiensis (Bti) toxin Cry11Aa domain II loop α8 and Cyt1Aa loop ß6-αE peptides into the AeDNV genome to improve its mosquitocidal efficiency; protein expression was confirmed using nanoscale liquid chromatography coupled to tandem mass spectrometry (nano LC-MS/MS). Recombinant plasmids were transfected into mosquito C6/36 cell lines, and the expression of specific peptides was detected through RT-PCR. A toxicity bioassay against the first instar Aedes albopictus larvae revealed that the pathogenic activity of recombinant AeDNV was significantly higher and faster than the wild-type (wt) viruses, and mortality increased in a dose-dependent manner. The recombinant viruses were genetically stable and displayed growth phenotype and virus proliferation ability, similar to wild-type AeDNV. Our novel results offer further insights by combining two mosquitocidal pathogens to improve viral toxicity for mosquito control.


Assuntos
Aedes/efeitos dos fármacos , Aedes/virologia , Toxinas de Bacillus thuringiensis/toxicidade , Agentes de Controle Biológico , Densovirus/patogenicidade , Larva/efeitos dos fármacos , Mosquitos Vetores/efeitos dos fármacos , Animais , China , Densovirus/genética , Controle de Mosquitos/métodos , Mosquitos Vetores/virologia , Virulência/efeitos dos fármacos
12.
PLoS Negl Trop Dis ; 16(2): e0010206, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35139066

RESUMO

The tiger mosquito was introduced to the Eastern region of the Mediterranean basin more than twenty years ago. In Lebanon, it was first observed in 2002 in a limited number of locations mainly from the coastal area of the country. In the absence of national entomological control program, this invasive mosquito became an established species and is now considered in many localities, a source of nuisance because of its human biting behavior. Several entomological surveys were conducted to monitor the geographic spread and the seasonal dynamics of Aedes albopictus by collecting adult stages and by monitoring oviposition activity. Moreover, its susceptibility to the common groups of insecticides was assessed using WHO standard bioassays. Previous vector competence studies revealed that local strains were able to transmit Chikungunya and Dengue viruses. Due to the increased risk of Zika virus introduction in the country, we determined the competence of local populations to transmit this virus. Mapping results showed that Ae. albopictus is mainly spread in the relatively humid western versant of the Mount Lebanon chain reaching 1000m altitude, while it is absent from arid and semi-arid inland areas. Besides, this mosquito is active during 32 weeks from spring till the end of autumn. Local strains of the tiger mosquito are susceptible to pyrethroids and carbamates but resistant to organophosphates and organochlorines. They showed ability to transmit Zika virus; however, only 9% of females were capable to excrete the virus in their saliva at day 28 post infection. Current and previous observations highlight the need to establish a surveillance system in order to control this mosquito and monitor the potential introduction of related diseases.


Assuntos
Aedes/fisiologia , Espécies Introduzidas/estatística & dados numéricos , Mosquitos Vetores/fisiologia , Aedes/efeitos dos fármacos , Aedes/virologia , Distribuição Animal , Animais , Vírus da Dengue/genética , Vírus da Dengue/isolamento & purificação , Feminino , Inseticidas/farmacologia , Líbano , Masculino , Mosquitos Vetores/efeitos dos fármacos , Mosquitos Vetores/virologia , Piretrinas/farmacologia , Saliva/virologia , Estações do Ano , Zika virus/genética , Zika virus/isolamento & purificação
13.
Viruses ; 14(2)2022 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-35215815

RESUMO

Aedes aegypti mosquitoes are important vectors of several debilitating and deadly arthropod-borne (arbo) viruses, including Yellow Fever virus, Dengue virus, West Nile virus and Zika virus (ZIKV). Arbovirus transmission occurs when an infected mosquito probes the host's skin in search of a blood meal. Salivary proteins from mosquitoes help to acquire blood and have also been shown to enhance pathogen transmission in vivo and in vitro. Here, we evaluated the interaction of mosquito salivary proteins with ZIKV by surface plasmon resonance and enzyme-linked immunosorbent assay. We found that three salivary proteins AAEL000793, AAEL007420, and AAEL006347 bind to the envelope protein of ZIKV with nanomolar affinities. Similar results were obtained using virus-like particles in binding assays. These interactions have no effect on viral replication in cultured endothelial cells and keratinocytes. Additionally, we found detectable antibody levels in ZIKV and DENV serum samples against the recombinant proteins that interact with ZIKV. These results highlight complex interactions between viruses, salivary proteins and antibodies that could be present during viral transmissions.


Assuntos
Aedes/metabolismo , Proteínas de Insetos/metabolismo , Mosquitos Vetores/metabolismo , Proteínas e Peptídeos Salivares/metabolismo , Proteínas do Envelope Viral/metabolismo , Zika virus/metabolismo , Aedes/química , Aedes/genética , Aedes/virologia , Animais , Células Endoteliais/metabolismo , Células Endoteliais/virologia , Proteínas de Insetos/química , Proteínas de Insetos/genética , Queratinócitos/metabolismo , Queratinócitos/virologia , Cinética , Mosquitos Vetores/química , Mosquitos Vetores/genética , Mosquitos Vetores/virologia , Ligação Proteica , Proteínas e Peptídeos Salivares/química , Proteínas e Peptídeos Salivares/genética , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genética , Replicação Viral , Zika virus/química , Zika virus/genética
14.
mSphere ; 7(1): e0100321, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35171691

RESUMO

Arboviruses transmitted by mosquitoes are responsible for the death of millions of people each year. In addition to arboviruses, many insect-specific viruses (ISVs) have been discovered in mosquitoes in the last decade. ISVs, in contrast to arboviruses transmitted by mosquitoes to vertebrates, cannot replicate in vertebrate cells even when they are evolutionarily closely related to arboviruses. The alphavirus genus includes many arboviruses, although only a few ISVs have been discovered from this genus so far. Here, we investigate the interactions of a recently isolated insect-specific alphavirus, Agua Salud alphavirus (ASALV), with its mosquito host. RNA interference (RNAi) is one of the essential antiviral responses against arboviruses, although there is little knowledge on the interactions of RNAi with ISVs. Through the knockdown of transcripts of the different key RNAi pathway (small interfering RNA [siRNA], microRNA [miRNA], and P-element-induced wimpy testis [PIWI]-interacting RNA [piRNA]) proteins, we show the antiviral role of Ago2 (siRNA), Ago1 (miRNA), and Piwi4 proteins against ASALV in Aedes aegypti-derived cells. ASALV replication was increased in Dicer2 and Ago2 knockout cells, confirming the antiviral role of the siRNA pathway. In infected cells, mainly ASALV-specific siRNAs are produced, while piRNA-like small RNAs, with the characteristic nucleotide bias resulting from ping-pong amplification, are produced only in Dicer2 knockout cells. Taken together, ASALV interactions with the mosquito RNAi response differ from those of arthropod-borne alphaviruses in some aspects, although they also share some commonalities. Further research is needed to understand whether the identified differences can be generalized to other insect-specific alphaviruses. IMPORTANCE Mosquitoes are efficient vectors for many arboviruses that cause emergent infectious diseases in humans. Many insect-specific viruses (ISVs) that can infect mosquitoes but cannot infect vertebrates have been discovered in the last decade. ISVs have attracted great attention due to their potential use in mosquito or arbovirus control, by either decreasing mosquito fitness or restricting arbovirus replication and transmission to humans. However, ISV-mosquito interactions are not well understood. RNA interference (RNAi) is the most important innate immune response against many arboviruses, while it is unknown if it is antiviral against ISVs. Here, we investigate in detail the antiviral effect of the RNAi response in mosquitoes against an ISV for the first time. Using a recently isolated insect-specific alphavirus, we show that the regulation of virus replication was different from that for arthropod-borne alphaviruses despite some similarities. The differences in mosquito-virus interactions could drive the different transmission modes, which could eventually drive the evolution of arboviruses. Hence, an understanding of mosquito-ISV interactions can shed light on the ecology and evolution of both ISVs and the medically important arboviruses.


Assuntos
Aedes , Alphavirus , Arbovírus , Vírus de Insetos , MicroRNAs , Aedes/genética , Aedes/virologia , Alphavirus/genética , Animais , Antivirais , Arbovírus/fisiologia , Linhagem Celular , Mosquitos Vetores/virologia , Interferência de RNA , RNA de Cadeia Dupla , RNA Interferente Pequeno/genética
15.
Mol Cell Biochem ; 477(3): 815-832, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35059925

RESUMO

Dengue viruses (DENVs) are the viruses responsible for dengue infection which affects lungs, liver, heart and also other organs of individuals. DENVs consist of the group of four serotypically diverse dengue viruses transmitted in tropical and sub-tropical countries of world. Aedes mosquito is the principal vector which spread the infection from infected person to healthy humans. DENVs can cause different syndromes depending on serotype of virus which range from undifferentiated mild fever to dengue hemorrhagic fever resulting in vascular leakage due to release of cytokine and Dengue shock syndrome with fluid loss and hypotensive shock, or other severe manifestations such as bleeding and organ failure. Increase in dengue cases in pediatric population is a major concern. Transmission of dengue depends on various factors like temperature, rainfall, and distribution of Aedes aegypti mosquitoes. The present review describes a comprehensive overview of dengue, pathophysiology, diagnosis, treatment with an emphasis on potential of exosomes as biomarkers for early prediction of dengue in pediatrics.


Assuntos
Vírus da Dengue/metabolismo , Dengue/sangue , Exossomos/metabolismo , Aedes/virologia , Animais , Biomarcadores/sangue , Dengue/diagnóstico , Dengue/transmissão , Humanos , Mosquitos Vetores/virologia , Prognóstico
16.
PLoS Pathog ; 18(1): e1010202, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34990484

RESUMO

The exogenous small interfering RNA (exo-siRNA) pathway is a key antiviral mechanism in the Aedes aegypti mosquito, a widely distributed vector of human-pathogenic arboviruses. This pathway is induced by virus-derived double-stranded RNAs (dsRNA) that are cleaved by the ribonuclease Dicer 2 (Dcr2) into predominantly 21 nucleotide (nt) virus-derived small interfering RNAs (vsiRNAs). These vsiRNAs are used by the effector protein Argonaute 2 within the RNA-induced silencing complex to cleave target viral RNA. Dcr2 contains several domains crucial for its activities, including helicase and RNase III domains. In Drosophila melanogaster Dcr2, the helicase domain has been associated with binding to dsRNA with blunt-ended termini and a processive siRNA production mechanism, while the platform-PAZ domains bind dsRNA with 3' overhangs and subsequent distributive siRNA production. Here we analyzed the contributions of the helicase and RNase III domains in Ae. aegypti Dcr2 to antiviral activity and to the exo-siRNA pathway. Conserved amino acids in the helicase and RNase III domains were identified to investigate Dcr2 antiviral activity in an Ae. aegypti-derived Dcr2 knockout cell line by reporter assays and infection with mosquito-borne Semliki Forest virus (Togaviridae, Alphavirus). Functionally relevant amino acids were found to be conserved in haplotype Dcr2 sequences from field-derived Ae. aegypti across different continents. The helicase and RNase III domains were critical for silencing activity and 21 nt vsiRNA production, with RNase III domain activity alone determined to be insufficient for antiviral activity. Analysis of 21 nt vsiRNA sequences (produced by functional Dcr2) to assess the distribution and phasing along the viral genome revealed diverse yet highly consistent vsiRNA pools, with predominantly short or long sequence overlaps including 19 nt overlaps (the latter representing most likely true Dcr2 cleavage products). Combined with the importance of the Dcr2 helicase domain, this suggests that the majority of 21 nt vsiRNAs originate by processive cleavage. This study sheds new light on Ae. aegypti Dcr2 functions and properties in this important arbovirus vector species.


Assuntos
Aedes/imunologia , Aedes/virologia , Infecções por Alphavirus/imunologia , Ribonuclease III/imunologia , Aedes/genética , Animais , Análise Mutacional de DNA , Mosquitos Vetores/virologia , RNA Interferente Pequeno/imunologia , RNA Viral/imunologia , Ribonuclease III/genética , Vírus da Floresta de Semliki
17.
PLoS Negl Trop Dis ; 16(1): e0010075, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35007285

RESUMO

BACKGROUND: West Nile virus is a mosquito-borne flavivirus which has been posing continuous challenges to public health worldwide due to the identification of new lineages and clades and its ability to invade and establish in an increasing number of countries. Its current distribution, genetic variability, ecology, and epidemiological pattern in the African continent are only partially known despite the general consensus on the urgency to obtain such information for quantifying the actual disease burden in Africa other than to predict future threats at global scale. METHODOLOGY AND PRINCIPAL FINDINGS: References were searched in PubMed and Google Scholar electronic databases on January 21, 2020, using selected keywords, without language and date restriction. Additional manual searches of reference list were carried out. Further references have been later added accordingly to experts' opinion. We included 153 scientific papers published between 1940 and 2021. This review highlights: (i) the co-circulation of WNV-lineages 1, 2, and 8 in the African continent; (ii) the presence of diverse WNV competent vectors in Africa, mainly belonging to the Culex genus; (iii) the lack of vector competence studies for several other mosquito species found naturally infected with WNV in Africa; (iv) the need of more competence studies to be addressed on ticks; (iv) evidence of circulation of WNV among humans, animals and vectors in at least 28 Countries; (v) the lack of knowledge on the epidemiological situation of WNV for 19 Countries and (vii) the importance of carrying out specific serological surveys in order to avoid possible bias on WNV circulation in Africa. CONCLUSIONS: This study provides the state of art on WNV investigation carried out in Africa, highlighting several knowledge gaps regarding i) the current WNV distribution and genetic diversity, ii) its ecology and transmission chains including the role of different arthropods and vertebrate species as competent reservoirs, and iii) the real disease burden for humans and animals. This review highlights the needs for further research and coordinated surveillance efforts on WNV in Africa.


Assuntos
Aedes/virologia , Culex/virologia , Carrapatos/virologia , Febre do Nilo Ocidental/epidemiologia , Febre do Nilo Ocidental/transmissão , África/epidemiologia , Animais , Humanos , Controle de Insetos/métodos , Mosquitos Vetores/virologia , Febre do Nilo Ocidental/patologia , Vírus do Nilo Ocidental/genética , Vírus do Nilo Ocidental/isolamento & purificação
18.
PLoS Negl Trop Dis ; 16(1): e0010119, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35020732

RESUMO

The primary dengue virus vectors, Aedes aegypti and Aedes albopictus, are primarily daytime biting mosquitoes. The risk of infection is suspected to be considerable in urban parks due to visitor traffic. Despite the importance of vector control for reducing dengue transmission, little information is available on vector populations in urban parks. The present study characterized mosquito habitats and estimated vector densities in the major urban parks in Ho Chi Minh City, Vietnam and compared them with those in adjacent residential areas. The prevalences of habitats where Aedes larvae were found were 43% and 9% for the parks and residential areas, respectively. The difference was statistically significant (prevalence ratio [PR]: 5.00, 95% CI: 3.85-6.49). The prevalences of positive larval habitats were significantly greater in the parks for both species than the residential areas (PR: 1.52, 95% CI: 1.04-2.22 for A. aegypti, PR: 10.10, 95% CI: 7.23-14.12 for A. albopictus). Larvae of both species were positively associated with discarded containers and planters. Aedes albopictus larvae were negatively associated with indoor habitats, but positively associated with vegetation shade. The adult density of A. aegypti was significantly less in the parks compared with the residential areas (rate ratio [RR]; 0.09, 95% CI: 0.05-0.16), while the density of A. albopictus was significantly higher in the parks (RR: 9.99, 95% CI: 6.85-14.59). When the species were combined, the density was significantly higher in the parks (RR: 2.50, 95% CI: 1.92-3.25). The urban parks provide suitable environment for Aedes mosquitoes, and A. albopictus in particular. Virus vectors are abundant in the urban parks, and the current vector control programs need to have greater consideration of urban parks.


Assuntos
Aedes/virologia , Dengue/transmissão , Mosquitos Vetores/virologia , Parques Recreativos/estatística & dados numéricos , Aedes/crescimento & desenvolvimento , Animais , Cidades , Dengue/epidemiologia , Vírus da Dengue , Ecossistema , Humanos , Larva , Densidade Demográfica , Vietnã/epidemiologia
19.
PLoS Negl Trop Dis ; 16(1): e0010069, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35020717

RESUMO

Chikungunya fever is an acute febrile illness that is often associated with severe polyarthralgia in humans. The disease is caused by chikungunya virus (CHIKV), a mosquito-borne alphavirus. Since its reemergence in 2004, the virus has spread throughout the tropical world and several subtropical areas affecting millions of people to become a global public health issue. Given the significant disease burden, there is a need for medical countermeasures and several vaccine candidates are in clinical development. To characterize the global epidemiology of chikungunya and inform vaccine development, we undertook a systematic literature review in MEDLINE and additional public domain sources published up to June 13, 2020 and assessed epidemiological trends from 1999 to 2020. Observational studies addressing CHIKV epidemiology were included and studies not reporting primary data were excluded. Only descriptive analyses were conducted. Of 3,883 relevant sources identified, 371 were eligible for inclusion. 46% of the included studies were published after 2016. Ninety-seven outbreak reports from 45 countries and 50 seroprevalence studies from 31 countries were retrieved, including from Africa, Asia, Oceania, the Americas, and Europe. Several countries reported multiple outbreaks, but these were sporadic and unpredictable. Substantial gaps in epidemiological knowledge were identified, specifically granular data on disease incidence and age-specific infection rates. The retrieved studies revealed a diversity of methodologies and study designs, reflecting a lack of standardized procedures used to characterize this disease. Nevertheless, available epidemiological data emphasized the challenges to conduct vaccine efficacy trials due to disease unpredictability. A better understanding of chikungunya disease dynamics with appropriate granularity and better insights into the duration of long-term population immunity is critical to assist in the planning and success of vaccine development efforts pre and post licensure.


Assuntos
Febre de Chikungunya/epidemiologia , Febre de Chikungunya/prevenção & controle , Vírus Chikungunya/imunologia , Aedes/virologia , Animais , Surtos de Doenças , Humanos , Mosquitos Vetores/virologia , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/virologia , Estudos Soroepidemiológicos , Vacinas Virais/imunologia
20.
PLoS Negl Trop Dis ; 16(1): e0010061, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35025860

RESUMO

BACKGROUND: Neglected tropical diseases (NTDs) primarily affect the poorest populations, often living in remote, rural areas, urban slums or conflict zones. Arboviruses are a significant NTD category spread by mosquitoes. Dengue, Chikungunya, and Zika are three arboviruses that affect a large proportion of the population in Latin and South America. The clinical diagnosis of these arboviral diseases is a difficult task due to the concurrent circulation of several arboviruses which present similar symptoms, inaccurate serologic tests resulting from cross-reaction and co-infection with other arboviruses. OBJECTIVE: The goal of this paper is to present evidence on the state of the art of studies investigating the automatic classification of arboviral diseases to support clinical diagnosis based on Machine Learning (ML) and Deep Learning (DL) models. METHOD: We carried out a Systematic Literature Review (SLR) in which Google Scholar was searched to identify key papers on the topic. From an initial 963 records (956 from string-based search and seven from a single backward snowballing procedure), only 15 relevant papers were identified. RESULTS: Results show that current research is focused on the binary classification of Dengue, primarily using tree-based ML algorithms. Only one paper was identified using DL. Five papers presented solutions for multi-class problems, covering Dengue (and its variants) and Chikungunya. No papers were identified that investigated models to differentiate between Dengue, Chikungunya, and Zika. CONCLUSIONS: The use of an efficient clinical decision support system for arboviral diseases can improve the quality of the entire clinical process, thus increasing the accuracy of the diagnosis and the associated treatment. It should help physicians in their decision-making process and, consequently, improve the use of resources and the patient's quality of life.


Assuntos
Infecções por Arbovirus/diagnóstico , Febre de Chikungunya/diagnóstico , Sistemas de Apoio a Decisões Clínicas , Dengue/diagnóstico , Infecção por Zika virus/diagnóstico , Aedes/virologia , Animais , Infecções por Arbovirus/tratamento farmacológico , Infecções por Arbovirus/virologia , Febre de Chikungunya/tratamento farmacológico , Vírus Chikungunya , Aprendizado Profundo , Dengue/tratamento farmacológico , Vírus da Dengue , Humanos , Mosquitos Vetores/virologia , Doenças Negligenciadas/virologia , América do Sul , Zika virus , Infecção por Zika virus/tratamento farmacológico
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