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1.
Viruses ; 13(7)2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34372606

RESUMO

As demonstrated with the novel coronavirus pandemic, rapid and accurate diagnosis is key to determine the clinical characteristic of a disease and to improve vaccine development. Once the infected person is identified, hematological findings may be used to predict disease outcome and offer the correct treatment. Rapid and accurate diagnosis and clinical parameters are pivotal to track infections during clinical trials and set protection status. This is also applicable for re-emerging diseases like dengue fever, which causes outbreaks in Asia and Latin America every 4 to 5 years. Some areas in the US are also endemic for the transmission of dengue virus (DENV), the causal agent of dengue fever. However, significant number of DENV infections in rural areas are diagnosed solely by clinical and hematological findings because of the lack of availability of ELISA or PCR-based tests or the infrastructure to implement them in the near future. Rapid diagnostic tests (RDT) are a less sensitive, yet they represent a timely way of detecting DENV infections. The purpose of this study was to determine whether there is an association between hematological findings and the probability for an NS1-based DENV RDT to detect the DENV NS1 antigen. We also aimed to describe the hematological parameters that are associated with the diagnosis through each test.


Assuntos
COVID-19/diagnóstico , COVID-19/epidemiologia , Dengue/diagnóstico , Adolescente , Adulto , Ásia/epidemiologia , Criança , Pré-Escolar , Colômbia/epidemiologia , Dengue/virologia , Vírus da Dengue/isolamento & purificação , Testes Diagnósticos de Rotina/métodos , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Masculino , Pandemias , Reação em Cadeia da Polimerase , Kit de Reagentes para Diagnóstico , SARS-CoV-2/isolamento & purificação , Adulto Jovem
2.
Genome Res ; 31(3): 512-528, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33419731

RESUMO

Although mosquitoes are major transmission vectors for pathogenic arboviruses, viral infection has little impact on mosquito health. This immunity is caused in part by mosquito RNA interference (RNAi) pathways that generate antiviral small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs). RNAi also maintains genome integrity by potently repressing mosquito transposon activity in the germline and soma. However, viral and transposon small RNA regulatory pathways have not been systematically examined together in mosquitoes. Therefore, we developed an integrated mosquito small RNA genomics (MSRG) resource that analyzes the transposon and virus small RNA profiles in mosquito cell cultures and somatic and gonadal tissues across four medically important mosquito species. Our resource captures both somatic and gonadal small RNA expression profiles within mosquito cell cultures, and we report the evolutionary dynamics of a novel Mosquito-Conserved piRNA Cluster Locus (MCpiRCL) made up of satellite DNA repeats. In the larger culicine mosquito genomes we detected highly regular periodicity in piRNA biogenesis patterns coinciding with the expansion of Piwi pathway genes. Finally, our resource enables detection of cross talk between piRNA and siRNA populations in mosquito cells during a response to virus infection. The MSRG resource will aid efforts to dissect and combat the capacity of mosquitoes to tolerate and spread arboviruses.

3.
Int J Mol Sci ; 21(18)2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32927629

RESUMO

Dengue is the most burdensome vector-borne viral disease in the world. Dengue virus (DENV), the etiological cause of dengue, is transmitted primarily by the Aedes aegypti mosquito. Like any arbovirus, the transmission cycle of dengue involves the complex interactions of a multitude of human and mosquito factors. One point during this transmission cycle that is rich in these interactions is the biting event by the mosquito, upon which its saliva is injected into the host. A number of components in mosquito saliva have been shown to play a pivotal role in the transmission of dengue, however one such component that is not as well characterized is extracellular vesicles. Here, using high-performance liquid chromatography in tandem with mass spectrometry, we show that dengue infection altered the protein cargo of Aedes aegypti extracellular vesicles, resulting in the packaging of proteins with infection-enhancing ability. Our results support the presence of an infection-dependent pro-viral protein packaging strategy that uses the differential packaging of pro-viral proteins in extracellular vesicles of Ae. aegypti saliva to promote transmission. These studies represent the first investigation into the function of Ae. aegypti extracellular vesicle cargo during dengue infection.


Assuntos
Aedes/metabolismo , Dengue/transmissão , Vesículas Extracelulares/metabolismo , Proteínas de Insetos/metabolismo , Mosquitos Vetores/metabolismo , Aedes/virologia , Animais , Células Cultivadas , Dengue/virologia , Vírus da Dengue , Feminino , Humanos , Mosquitos Vetores/virologia
4.
Int J Mol Sci ; 21(18)2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32916828

RESUMO

Aedes aegypti is the primary mosquito vector of several human arboviruses, including the dengue virus (DENV). Vector control is the principal intervention to decrease the transmission of these viruses. The characterization of molecules involved in the mosquito physiological responses to blood-feeding may help identify novel targets useful in designing effective control strategies. In this study, we evaluated the in vivo effect of feeding adult female mosquitoes with human red blood cells reconstituted with either heat-inactivated (IB) or normal plasma (NB). The RNA-seq based transcript expression of IB and NB mosquitoes was compared against sugar-fed (SF) mosquitoes. In in vitro experiments, we treated Aag2 cells with a recombinant version of complement proteins (hC3 or hC5a) and compared transcript expression to untreated control cells after 24 h. The transcript expression analysis revealed that human complement proteins modulate approximately 2300 transcripts involved in multiple biological functions, including immunity. We also found 161 upregulated and 168 downregulated transcripts differentially expressed when human complement protein C3 (hC3) and human complement protein C5a (hC5a) treated cells were compared to the control untreated cells. We conclude that active human complement induces significant changes to the transcriptome of Ae. aegypti mosquitoes, which may influence the physiology of these arthropods.


Assuntos
Aedes/metabolismo , Mosquitos Vetores/metabolismo , Transcriptoma , Aedes/imunologia , Animais , Complemento C3 , Complemento C5a , Feminino , Humanos , Mosquitos Vetores/imunologia
5.
ACS Infect Dis ; 6(8): 2023-2028, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32609483

RESUMO

Aedes mosquitoes vector many viruses with divergent characteristics, yet the criteria needed for a virus to be vectored by an arthropod remain unknown. The intracellular cholesterol transporter protein Niemann-Pick C1 (NPC1) has been identified as the necessary entry receptor for filoviruses such as Ebola and Marburg viruses. While homologues of NPC1 are observed in mosquitoes, currently no filovirus has been identified as circulating in mosquitoes. This work aimed at increasing the understanding of the mosquito vector by examining the capability of a virus to gain the ability to enter mosquito cells. We developed a model system of Aedes cells expressing human NPC1 (hNPC1) and attempted to infect these cells with recombinant vesicular stomatitis virus expressing the Ebola virus glycoprotein. As compared to the control cells, no significant increase in infection was observed in cells expressing hNPC1, demonstrating that the expression of human NPC1 alone is not sufficient to support filovirus infection, and that host factors other than NPC1 determine filovirus susceptibility of mosquito cells.


Assuntos
Aedes , Proteína C1 de Niemann-Pick , Animais , Linhagem Celular , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Mosquitos Vetores , Permissividade , Receptores Virais/metabolismo , Internalização do Vírus
6.
Parasit Vectors ; 13(1): 128, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32171303

RESUMO

BACKGROUND: Zika virus (ZIKV) is transmitted to humans during the bite of an infected mosquito. In a scenario of globalization and climate change, the frequency of outbreaks has and will increase in areas with competent vectors, revealing a need for continuous improvement of ZIKV detection tools in vector populations. A simple, rapid and sensitive assay for viral detection is quantitative reverse transcription polymerase chain reaction (qRT-PCR), yet oligos optimized for ZIKV detection in mammalian cells and samples have repeatedly shown high background when used on mosquito ribonucleic acid (RNA). In this paper, we present a one-step qRT-PCR protocol that allows for the detection of ZIKV in mosquitoes and for the evaluation of gene expression from the same mosquito sample and RNA. This assay is a less expensive qRT-PCR approach than that most frequently used in the literature and has a much lower background, allowing confident detection. METHODS: Our new oligo design to detect ZIKV RNA included in silico analysis of both viral and mosquito (Ae. aegypti and Ae. albopictus) genomes, targeting sequences conserved between Asian and African ZIKV lineages, but not matching Aedes genomes. This assay will allow researchers to avoid nonspecific amplification in insect samples due to viral integration into the mosquito genome, a phenomenon known to happen in wild and colonized populations of mosquitoes. Standard curves constructed with in vitro transcribed ZIKV RNA were used to optimize the sensitivity, efficiency and reproducibility of the assay. RESULTS: Finally, the assay was used with success to detect both ZIKV RNA in infected mosquitoes and to detect expression of the Defensin A gene, an antimicrobial peptide (AMP) involved in Aedes aegypti immune response to virus infection. CONCLUSIONS: The experimental approach to detect ZIKV RNA in Aedes aegypti presented here has demonstrated to be specific, sensitive and reliable, and additionally it allows for the analysis of mosquito gene expression during ZIKV infection.


Assuntos
Aedes/virologia , Regulação Viral da Expressão Gênica , Mosquitos Vetores/virologia , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real/métodos , Infecção por Zika virus/diagnóstico , Zika virus/genética , Zika virus/isolamento & purificação , Aedes/genética , Animais , Chlorocebus aethiops , Culicidae/virologia , RNA Viral/genética , Reprodutibilidade dos Testes , Alinhamento de Sequência , Células Vero , Proteínas não Estruturais Virais/genética , Infecção por Zika virus/virologia
8.
Sci Rep ; 9(1): 6352, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015516

RESUMO

Aedes aegypti is the primary vector of a number of viruses pathogenic to humans including dengue virus (DENV). DENV infection leads to widespread transcriptomic and proteomic alterations in mosquito cells. Here we identified alterations to the mosquito cell secretome during DENV infection by performing liquid chromatography tandem mass spectrometry. We found that an extracellular fragment of low-density lipoprotein receptor-related protein 1 (LRP-1) was present during infection. Previous literature suggests that LRP-1 regulates cholesterol homeostasis. Therefore, we hypothesized that DENV modifies LRP-1 protein expression to maintain host-derived intracellular cholesterol, which would facilitate virus replication within membrane-associated replication compartments. Accordingly, stimuli that are present during flavivirus infection reduced LRP-1 protein expression. We also found that dsRNA knockdown of LRP-1 increased intracellular cholesterol and DENV viral RNA. Further, depletion of intracellular lipids reduced infection. Together, these data suggest that DENV reduces LRP-1 protein expression, possibly through regulated intramembrane proteolysis (RIP), to increase intracellular cholesterol and facilitate replication in Ae. aegypti.


Assuntos
Aedes/virologia , Vírus da Dengue/fisiologia , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Replicação Viral/fisiologia , Animais , Linhagem Celular , Colesterol/metabolismo , Dengue/virologia , Proteínas de Insetos/metabolismo , Peptídeos/metabolismo , RNA Viral/metabolismo
9.
Insects ; 10(2)2019 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-30717390

RESUMO

Dengue virus (DENV) is transmitted by mosquitoes and is a major public health concern. The study of innate mosquito defense mechanisms against DENV have revealed crucial roles for the Toll, Imd, JAK-STAT, and RNAi pathways in mediating DENV in the mosquito. Often overlooked in such studies is the role of intrinsic cellular defense mechanisms that we hypothesize to work in concert with the classical immune pathways to affect organismal defense. Our understanding of the molecular interaction of DENV with mosquito host cells is limited, and we propose to expand upon the recent results from a genome-scale, small interfering RNA (siRNA)-based study that identified mammalian host proteins associated with resistance to dengue/West Nile virus (DENV/WNV) infection. The study identified 22 human DENV/WNV resistance genes (DVR), and we hypothesized that a subset would be functionally conserved in Aedes aegypti mosquitoes, imparting cellular defense against flaviviruses in this species. We identified 12 homologs of 22 human DVR genes in the Ae. aegypti genome. To evaluate their possible role in cellular resistance/antiviral defense against DENV, we used siRNA silencing targeted against each of the 12 homologs in an Ae. aegypti cell line (Aag2) infected with DENV2 and identified that silencing of the two candidates, AeFKBP1 and AeATCAY, homologs of human FKBP1B and ATCAY, were associated with a viral increase. We then used dsRNA to silence each of the two genes in adult mosquitoes to validate the observed antiviral functions in vivo. Depletion of AeFKBP1 or AeATCAY increased viral dissemination through the mosquito at 14 days post-infection. Our results demonstrated that AeFKBP1 and AeATCAY mediate resistance to DENV akin to what has been described for their homologs in humans. AeFKBP1 and AeATCAY provide a rare opportunity to elucidate a DENV-resistance mechanism that may be evolutionarily conserved between humans and Ae. aegypti.

10.
J Vis Exp ; (143)2019 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-30735189

RESUMO

The recent emergence of the flavivirus Zika and neurological complications, such as Guillain-Barré syndrome and microcephaly in infants, has brought serious public safety concerns. Among the risk factors, antibody-dependent enhancement (ADE) poses the most significant threat, as the recent re-emergence of the Zika virus (ZIKV) is primarily in areas where the population has been exposed and is in a state of pre-immunity to other closely related flaviviruses, especially dengue virus (DENV). Here, we describe a protocol for quantifying the effect of human serum antibodies against DENV on ZIKV infection in primary human cells or cell lines.


Assuntos
Anticorpos Antivirais/imunologia , Anticorpos Facilitadores/imunologia , Zika virus/imunologia , Dengue/imunologia , Dengue/virologia , Vírus da Dengue/imunologia , Humanos , Soros Imunes , Macrófagos/virologia , Temperatura , Células U937 , Infecção por Zika virus/sangue , Infecção por Zika virus/imunologia , Infecção por Zika virus/virologia
11.
PLoS One ; 14(1): e0208455, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30601814

RESUMO

Dengue virus (DENV) is an arbovirus responsible for a significant number of deaths in Latin America. This virus is transmitted through the bite of Aedes aegypti, the main mosquito vector, and Ae. albopictus. During blood uptake, the mosquito injects its saliva into the host to facilitate the feeding process. Mosquito saliva contains potent immunogens capable of inducing antibody production directly related to mosquito bite exposure intensity and disease risk. In this study, we first determined the DENV infection status by two different DENV non-structural protein 1 (NS1) based rapid tests and qRT-PCR, then measured the levels of IgG1 and IgG4 antibodies against salivary proteins of Ae. aegypti female mosquitoes in volunteers living in a dengue endemic area. Our results show that people with a positive DENV diagnosis present higher levels of IgG4 antibodies than people with a negative diagnostic test, and that these antibody levels were higher in people with secondary DENV infections. With this study, we show that detection of IgG4 antibodies against mosquito saliva may be a reliable method to evaluate the risk of dengue infection.


Assuntos
Aedes/imunologia , Dengue/epidemiologia , Imunoglobulina G/imunologia , Proteínas e Peptídeos Salivares/imunologia , Adolescente , Adulto , Animais , Formação de Anticorpos/imunologia , Antígenos Virais/imunologia , Criança , Pré-Escolar , Colômbia/epidemiologia , Feminino , Humanos , Lactente , Pessoa de Meia-Idade , Fatores de Risco , Glândulas Salivares/metabolismo , Proteínas não Estruturais Virais/metabolismo , Adulto Jovem
12.
J Immunol ; 201(6): 1735-1747, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-30045970

RESUMO

Lymph node (LN) expansion during an immune response is a complex process that involves the relaxation of the fibroblastic network, germinal center formation, and lymphatic vessel growth. These processes require the stromal cell network of the LN to act deliberately to accommodate the influx of immune cells to the LN. The molecular drivers of these processes are not well understood. Therefore, we asked whether the immediate cytokines type 1 IFN produced during viral infection influence the lymphatic network of the LN in mice. We found that following an IFN-inducing stimulus such as viral infection or polyI:C, programmed cell death ligand 1 (PD-L1) expression is dynamically upregulated on lymphatic endothelial cells (LECs). We found that reception of type 1 IFN by LECs is important for the upregulation of PD-L1 of mouse and human LECs and the inhibition of LEC expansion in the LN. Expression of PD-L1 by LECs is also important for the regulation of LN expansion and contraction after an IFN-inducing stimulus. We demonstrate a direct role for both type 1 IFN and PD-L1 in inhibiting LEC division and in promoting LEC survival. Together, these data reveal a novel mechanism for the coordination of type 1 IFN and PD-L1 in manipulating LEC expansion and survival during an inflammatory immune response.


Assuntos
Antígeno B7-H1/imunologia , Proliferação de Células , Células Endoteliais/imunologia , Endotélio Linfático/imunologia , Interferon Tipo I/imunologia , Animais , Antígeno B7-H1/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Sobrevivência Celular/imunologia , Células Endoteliais/patologia , Endotélio Linfático/patologia , Humanos , Inflamação/genética , Inflamação/imunologia , Inflamação/patologia , Interferon Tipo I/genética , Camundongos , Camundongos Knockout , Poli I-C/farmacologia
13.
Front Public Health ; 6: 111, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29868532

RESUMO

Background: Dengue is one of the most geographically significant mosquito-borne viral diseases transmitted by Aedes mosquitoes. During blood feeding, mosquitoes deposit salivary proteins that induce antibody responses. These can be related to the intensity of exposure to bites. Some mosquito salivary proteins, such as D7 proteins, are known as potent allergens. The antibody response to D7 proteins can be used as a marker to evaluate the risk of exposure and disease transmission and provide critical information for understanding the dynamics of vector-host interactions. Methods: The study was conducted at the Los Patios Hospital, Cucuta, Norte de Santander, Colombia. A total of 63 participants were enrolled in the study. Participants were categorized into three disease status groups, age groups, and socioeconomic strata. The level of IgG antibodies against D7 Aedes proteins was determined by ELISA. We used a statistical approach to determine if there is an association between antibody levels and factors such as age, living conditions, and dengue virus (DENV) infection. Results: We found that IgG antibodies against D7 proteins were higher in non-DENV infected individuals in comparison to DENV-infected participants. Also, the age factor showed a significant positive correlation with IgG antibodies against D7 proteins, and the living conditions (socioeconomic stratification), in people aged 20 years or older, are a statistically significant factor in the variability of IgG antibodies against D7 proteins. Conclusion: This pilot study represents the first approximation to elucidate any correlation between the antibody response against mosquito D7 salivary proteins and its correlation with age, living conditions, and DENV infection in a dengue endemic area.

14.
Proc Natl Acad Sci U S A ; 115(28): E6604-E6613, 2018 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-29946031

RESUMO

Dengue virus (DENV) is a mosquito-borne flavivirus that causes dengue fever in humans, worldwide. Using in vitro cell lines derived from Aedes albopictus and Aedes aegypti, the primary vectors of DENV, we report that DENV2/DENV3-infected cells secrete extracellular vesicles (EVs), including exosomes, containing infectious viral RNA and proteins. A full-length DENV2 genome, detected in arthropod EVs, was infectious to naïve mosquito and mammalian cells, including human-skin keratinocytes and blood endothelial cells. Cryo-electron microscopy showed mosquito EVs with a size range from 30 to 250 nm. Treatments with RNase A, Triton X-100, and 4G2 antibody-bead binding assays showed that infectious DENV2-RNA and proteins are contained inside EVs. Viral plaque formation and dilution assays also showed securely contained infectious viral RNA and proteins in EVs are transmitted to human cells. Up-regulated HSP70 upon DENV2 infection showed no role in viral replication and transmission through EVs. In addition, qRT-PCR and immunoblotting results revealed that DENV2 up-regulates expression of a mosquito tetraspanin-domain-containing glycoprotein, designated as Tsp29Fb, in A. aegypti mosquitoes, cells, and EVs. RNAi-mediated silencing and antibody blocking of Tsp29Fb resulted in reduced DENV2 loads in both mosquito cells and EVs. Immunoprecipitation showed Tsp29Fb to directly interact with DENV2 E-protein. Furthermore, treatment with GW4869 (exosome-release inhibitor) affected viral burden, direct interaction of Tsp29Fb with E-protein and EV-mediated transmission of viral RNA and proteins to naïve human cells. In summary, we report a very important finding on EV-mediated transmission of DENV2 from arthropod to mammalian cells through interactions with an arthropod EVs-enriched marker Tsp29Fb.


Assuntos
Vírus da Dengue , Dengue , Vesículas Extracelulares , Proteínas de Insetos , Proteínas do Envelope Viral , Aedes , Animais , Linhagem Celular , Dengue/genética , Dengue/metabolismo , Dengue/transmissão , Vírus da Dengue/genética , Vírus da Dengue/metabolismo , Vírus da Dengue/patogenicidade , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/virologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Camundongos , Domínios Proteicos , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo
15.
J Gen Virol ; 98(7): 1702-1712, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28691657

RESUMO

Zika virus (ZIKV) is a mosquito-borne flavivirus that has recently been responsible for a serious outbreak of disease in South and Central America. Infection with ZIKV has been associated with severe neurological symptoms and the development of microcephaly in unborn fetuses. Many of the regions involved in the current outbreak are known to be endemic for another flavivirus, dengue virus (DENV), which indicates that a large percentage of the population may have pre-existing DENV immunity. Thus, it is vital to investigate what impact pre-existing DENV immunity has on ZIKV infection. Here, we use primary human myeloid cells as a model for ZIKV enhancement in the presence of DENV antibodies. We show that sera containing DENV antibodies from individuals living in a DENV-endemic area are able to enhance ZIKV infection in a human macrophage-derived cell line and primary human macrophages. We also demonstrate altered pro-inflammatory cytokine production in macrophages with enhanced ZIKV infection. Our study indicates an important role for pre-existing DENV immunity on ZIKV infection in primary human immune cells and establishes a relevant in vitro model to study ZIKV antibody-dependent enhancement.


Assuntos
Anticorpos Antivirais/imunologia , Anticorpos Facilitadores/imunologia , Vírus da Dengue/imunologia , Macrófagos/imunologia , Infecção por Zika virus/patologia , Zika virus/imunologia , Adulto , Linhagem Celular Tumoral , Criança , Pré-Escolar , Reações Cruzadas/imunologia , Citocinas/biossíntese , Dengue/imunologia , Dengue/virologia , Surtos de Doenças , Feminino , Humanos , Lactente , Masculino , Células U937 , Infecção por Zika virus/imunologia , Infecção por Zika virus/virologia
16.
Viruses ; 9(7)2017 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-28644404

RESUMO

Dengue virus (DENV) is a mosquito-borne flavivirus that causes significant global human disease and mortality. One approach to develop treatments for DENV infection and the prevention of severe disease is through investigation of natural medicines. Inflammation plays both beneficial and harmful roles during DENV infection. Studies have proposed that the oxidative stress response may be one mechanism responsible for triggering inflammation during DENV infection. Thus, blocking the oxidative stress response could reduce inflammation and the development of severe disease. Garlic has been shown to both reduce inflammation and affect the oxidative stress response. Here, we show that the garlic active compounds diallyl disulfide (DADS), diallyl sulfide (DAS) and alliin reduced inflammation during DENV infection and show that this reduction is due to the effects on the oxidative stress response. These results suggest that garlic could be used as an alternative treatment for DENV infection and for the prevention of severe disease development.


Assuntos
Compostos Alílicos/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Cisteína/análogos & derivados , Vírus da Dengue/crescimento & desenvolvimento , Dissulfetos/farmacologia , Alho/química , Sulfetos/farmacologia , Compostos Alílicos/isolamento & purificação , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Linhagem Celular , Cisteína/isolamento & purificação , Cisteína/farmacologia , Dissulfetos/isolamento & purificação , Interações Hospedeiro-Patógeno , Humanos , Estresse Oxidativo/efeitos dos fármacos , Sulfetos/isolamento & purificação
17.
DNA Cell Biol ; 36(6): 423-427, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28486041

RESUMO

Dengue is currently regarded as the most common arthropod-borne viral disease in tropical and subtropical areas, with an estimated 50-100 million infections occurring each year. Nearly all patients experience a self-limiting clinical course; however, the illness ranges from undifferentiated fever to severe hemorrhagic fever with or without shock syndrome complications. There are several immune cells associated with the pathogenesis of dengue virus (DENV) infection and systemic spread, including dendritic cells, macrophages, and mast cells (MCs). MCs are widely recognized for their immune functions and as cellular regulators of vascular integrity in human skin. Furthermore, these cells are able to detect DENV, which results in activation and degranulation of potent vasoactive mediators prestored in the granules. These mediators can act directly on vascular endothelium, increasing permeability and inducing vascular leakage. This review is designed to present an insight into the role of MCs during DENV infection and the dual functions in immune protection and contribution to the most severe forms of dengue.


Assuntos
Vírus da Dengue/fisiologia , Mastócitos/imunologia , Mastócitos/virologia , Animais , Dengue/etiologia , Dengue/imunologia , Humanos
18.
J Immunol ; 197(11): 4382-4391, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27799312

RESUMO

Dengue virus (DENV) is a mosquito-borne flavivirus that causes serious global human disease and mortality. Skin immune cells are an important component of initial DENV infection and systemic spread. Here, we show that mast cells are a target of DENV in human skin and that DENV infection of skin mast cells induces degranulation and alters cytokine and growth factor expression profiles. Importantly, to our knowledge, we also demonstrate for the first time that DENV localizes within secretory granules in infected skin mast cells. In addition, DENV within extracellular granules was infectious in vitro and in vivo, trafficking through lymph to draining lymph nodes in mice. We demonstrate an important role for human skin mast cells in DENV infection and identify a novel mechanism for systemic spread of DENV infection from the initial peripheral mosquito injection site.


Assuntos
Degranulação Celular/imunologia , Vírus da Dengue/imunologia , Dengue/imunologia , Mastócitos/imunologia , Vesículas Secretórias/imunologia , Pele/imunologia , Animais , Citocinas/imunologia , Dengue/patologia , Humanos , Linfonodos/imunologia , Linfonodos/patologia , Linfonodos/virologia , Mastócitos/patologia , Mastócitos/virologia , Camundongos , Vesículas Secretórias/patologia , Vesículas Secretórias/virologia , Pele/patologia , Pele/virologia
19.
Front Immunol ; 7: 380, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27746778

RESUMO

Chronic exposure to antigens may favor the production of IgG4 antibodies over other antibody types. Recent studies have shown that up to a 30% of normal human IgG4 is bi-specific and is able to recognize two antigens of different nature. A requirement for this specificity is the presence of both eliciting antigens in the same time and at the same place where the immune response is induced. During transmission of most vector-borne diseases, the pathogen is delivered to the vertebrate host along with the arthropod saliva during blood feeding and previous studies have shown the existence of IgG4 antibodies against mosquito salivary allergens. However, there is very little ongoing research or information available regarding IgG4 bi-specificity with regard to infectious disease, particularly during immune responses to vector-borne diseases, such as malaria, filariasis, or dengue virus infection. Here, we provide background information and present our hypothesis that IgG4 may not only be a useful tool to measure exposure to infected mosquito bites, but that these bi-specific antibodies may also play an important role in modulation of the immune response against malaria and other vector-borne diseases in endemic settings.

20.
Parasit Vectors ; 9(1): 516, 2016 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-27664127

RESUMO

Infectious diseases caused by arboviruses (viruses transmitted by arthropods) are undergoing unprecedented epidemic activity and geographic expansion. With the recent introduction of West Nile virus (1999), chikungunya virus (2013) and Zika virus (2015) to the Americas, stopping or even preventing the expansion of viruses into susceptible populations is an increasing concern. With a few exceptions, available vaccines protecting against arboviral infections are nonexistent and current disease prevention relies on vector control interventions. However, due to the emergence of and rapidly spreading insecticide resistance, different disease control methods are needed. A feasible method of reducing emerging tropical diseases is the implementation of vaccines that prevent or decrease viral infection in the vector. These vaccines are designated 'transmission blocking vaccines', or TBVs. Here, we summarize previous TBV work, discuss current research on arboviral TBVs and present several promising TBV candidates.

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