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1.
PLoS Negl Trop Dis ; 14(8): e0008660, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32866199

RESUMO

Aedes mosquitoes can transmit dengue and several other severe vector-borne viral diseases, thereby influencing millions of people worldwide. Insects primarily control and clear the viral infections via their innate immune systems. Mitogen-Activated Protein Kinases (MAPKs) and antimicrobial peptides (AMPs) are both evolutionarily conserved components of the innate immune systems. In this study, we investigated the role of MAPKs in Aedes mosquitoes following DENV infection by using genetic and pharmacological approaches. We demonstrated that knockdown of ERK, but not of JNK or p38, significantly enhances the viral replication in Aedes mosquito cells. The Ras/ERK signaling is activated in both the cells and midguts of Aedes mosquitoes following DENV infection, and thus plays a role in restricting the viral infection, as both genetic and pharmacological activation of the Ras/ERK pathway significantly decreases the viral titers. In contrast, inhibition of the Ras/ERK pathway enhances DENV infection. In addition, we identified a signaling crosstalk between the Ras/ERK pathway and DENV-induced AMPs in which defensin C participates in restricting DENV infection in Aedes mosquitoes. Our results reveal that the Ras/ERK signaling pathway couples AMPs to mediate the resistance of Aedes mosquitoes to DENV infection, which provides a new insight into understanding the crosstalk between MAPKs and AMPs in the innate immunity of mosquito vectors during the viral infection.


Assuntos
Aedes/virologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Vírus da Dengue/imunologia , Quinases de Proteína Quinase Ativadas por Mitógeno/farmacologia , Mosquitos Vetores/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Anti-Infecciosos/farmacologia , Linhagem Celular , Sistema Digestório/virologia , Feminino , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Imunidade Inata , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Mosquitos Vetores/virologia , Carga Viral , Replicação Viral/efeitos dos fármacos
2.
BMC Infect Dis ; 20(1): 639, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867694

RESUMO

BACKGROUND: Dengue fever is an arthropod vector-borne disease transmitted to humans by infected Aedes mosquitoes. Ethiopia has a favorable ecology for arthropods and report high burden of acute febrile illnesses. However, the contribution of arboviral infections to the burden of acute febrile illnesses is barely known. In this study the seropositivity to dengue virus infection and associated risk factors were assessed in Arba Minch districts, southern Ethiopia. METHODS: An institution based cross-sectional study was conducted in a consecutive group of 529 acute febrile patients between May to August 2016. Socio-demographic data, residence place and clinical signs and symptoms were collected using structured questionnaires. Sera were tested for anti-dengue IgG and IgM using Euroimmune indirect immunofluorescent assay. Data analysis was done using SPSS V-20 (IBM Corp, 2012). P-value < 0.05 was taken as statistically significant. RESULT: Seropositivity was 25.1% (133/529) and 8.1% (43/529) for anti- IgG and IgM respectively. CONCLUSION: The high IgM prevalence detected indicate the probability of active transmission with a potential of public health significance that calls for a proactive follow up of the communities in the study area to forecast and avert the risk.


Assuntos
Anticorpos Antivirais/sangue , Vírus da Dengue/imunologia , Dengue/sangue , Dengue/epidemiologia , Febre/sangue , Febre/epidemiologia , Adolescente , Adulto , Animais , Estudos Transversais , Dengue/diagnóstico , Dengue/virologia , Etiópia/epidemiologia , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
3.
PLoS Pathog ; 16(8): e1008754, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32776975

RESUMO

Arbovirus infection of Aedes aegypti salivary glands (SGs) determines transmission. However, there is a dearth of knowledge on SG immunity. Here, we characterized SG immune response to dengue, Zika and chikungunya viruses using high-throughput transcriptomics. We also describe a transcriptomic response associated to apoptosis, blood-feeding and lipid metabolism. The three viruses differentially regulate components of Toll, Immune deficiency (IMD) and c-Jun N- terminal Kinase (JNK) pathways. However, silencing of the Toll and IMD pathway components showed variable effects on SG infection by each virus. In contrast, regulation of the JNK pathway produced consistent responses in both SGs and midgut. Infection by the three viruses increased with depletion of the activator Kayak and decreased with depletion of the negative regulator Puckered. Virus-induced JNK pathway regulates the complement factor, Thioester containing protein-20 (TEP20), and the apoptosis activator, Dronc, in SGs. Individual and co-silencing of these genes demonstrate their antiviral effects and that both may function together. Co-silencing either TEP20 or Dronc with Puckered annihilates JNK pathway antiviral effect. Upon infection in SGs, TEP20 induces antimicrobial peptides (AMPs), while Dronc is required for apoptosis independently of TEP20. In conclusion, we revealed the broad antiviral function of JNK pathway in SGs and showed that it is mediated by a TEP20 complement and Dronc-induced apoptosis response. These results expand our understanding of the immune arsenal that blocks arbovirus transmission.


Assuntos
Aedes/imunologia , Apoptose , Febre de Chikungunya/imunologia , Proteínas do Sistema Complemento/imunologia , Dengue/imunologia , Sistema de Sinalização das MAP Quinases , Glândulas Salivares/imunologia , Infecção por Zika virus/imunologia , Aedes/virologia , Animais , Febre de Chikungunya/metabolismo , Febre de Chikungunya/prevenção & controle , Febre de Chikungunya/virologia , Vírus Chikungunya/imunologia , Proteínas do Sistema Complemento/metabolismo , Dengue/metabolismo , Dengue/prevenção & controle , Dengue/virologia , Vírus da Dengue/imunologia , Feminino , Interações Hospedeiro-Patógeno , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Insetos Vetores/imunologia , Insetos Vetores/virologia , Glândulas Salivares/virologia , Transcriptoma , Replicação Viral , Zika virus/imunologia , Infecção por Zika virus/metabolismo , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/virologia
4.
Science ; 369(6507): 1123-1128, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32855339

RESUMO

The Zika pandemic sparked intense interest in whether immune interactions among dengue virus serotypes 1 to 4 (DENV1 to -4) extend to the closely related Zika virus (ZIKV). We investigated prospective pediatric cohorts in Nicaragua that experienced sequential DENV1 to -3 (2004 to 2015), Zika (2016 to 2017), and DENV2 (2018 to 2020) epidemics. Risk of symptomatic DENV2 infection and severe disease was elevated by one prior ZIKV infection, one prior DENV infection, or one prior DENV infection followed by one ZIKV infection, compared with being flavivirus-naïve. By contrast, multiple prior DENV infections reduced dengue risk. Further, although high preexisting anti-DENV antibody titers protected against DENV1, DENV3, and ZIKV disease, intermediate titers induced by previous ZIKV or DENV infection enhanced future risk of DENV2 disease and severity, as well as DENV3 severity. The observation that prior ZIKV infection can modulate dengue disease severity like a DENV serotype poses challenges to development of dengue and Zika vaccines.


Assuntos
Vírus da Dengue/imunologia , Dengue Grave/epidemiologia , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/imunologia , Zika virus/imunologia , Anticorpos Antivirais/sangue , Vacinas contra Dengue/imunologia , Humanos , Imunogenicidade da Vacina , Nicarágua/epidemiologia , Risco , Sorogrupo
5.
PLoS Negl Trop Dis ; 14(8): e0008535, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32813703

RESUMO

Dengue fever occurs worldwide and about 1% of cases progress to severe haemorrhage and shock. Dengue is endemic in Guatemala and its surveillance system could document long term trends. We analysed 17 years of country-wide dengue surveillance data in Guatemala to describe epidemiological trends from 2000 to 2016.Data from the national dengue surveillance database were analysed to describe dengue serotype frequency, seasonality, and outbreaks. We used Poisson regression models to compare the number of cases each year with subsequent years and to estimate incidence ratios within serotype adjusted by age and gender. 91,554 samples were tested. Dengue was confirmed by RT-qPCR, culture or NS1-ELISA in 7097 (7.8%) cases and was IgM ELISA-positive in 19,290 (21.1%) cases. DENV1, DENV2, DENV3, and DENV4 were detected in 2218 (39.5%), 2580 (45.9%), 591 (10.5%), and 230 (4.1%) cases. DENV1 and DENV2 were the predominant serotypes, but all serotypes caused epidemics. The largest outbreak occurred in 2010 with 1080 DENV2 cases reported. The incidence was higher among adults during epidemic years, with significant increases in 2005, 2007, and 2013 DENV1 outbreaks, the 2010 DENV2 and 2003 DENV3 outbreaks. Adults had a lower incidence immediately after epidemics, which is likely linked to increased immunity.


Assuntos
Dengue/diagnóstico , Dengue/epidemiologia , Adolescente , Adulto , Anticorpos Antivirais/imunologia , Criança , Pré-Escolar , Dengue/imunologia , Vírus da Dengue/imunologia , Surtos de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Guatemala/epidemiologia , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Sorogrupo , Sorotipagem/métodos , Adulto Jovem
6.
Mem Inst Oswaldo Cruz ; 115: e200225, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32813814

RESUMO

In the near future, the overlap of Coronavirus disease 2019 (COVID-19) and dengue epidemics is a concrete threat in tropical regions. Co-epidemics of COVID-19 and dengue could be an overwhelming challenge for health systems in low- and middle-income countries. In this work, we investigated potential serological cross-reactions between COVID-19 and dengue patients. Among 32 COVID-19 positive sera, no positive Dengue virus (DENV) IgG/IgM results were observed. On the other hand, one false-positive result was observed among 44 DENV-positive sera tested for COVID-19 antibodies with each of the two rapid tests used. Further data on accuracy of COVID-19 diagnostic test are urgently warranted.


Assuntos
Anticorpos Antivirais/imunologia , Infecções por Coronavirus/imunologia , Reações Cruzadas , Dengue/imunologia , Pneumonia Viral/imunologia , Betacoronavirus/imunologia , Vírus da Dengue/imunologia , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Pandemias
7.
BMC Infect Dis ; 20(1): 580, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32762658

RESUMO

BACKGROUND: Dengue virus (DENV) causes the hospitalisation of an estimated 500,000 people every year. Outbreaks can severely stress healthcare systems, especially in rural settings. It is difficult to discriminate patients who need to be hospitalized from those that do not. Earlier work identified thrombocyte count and subsequent function as a promising prognostic marker of DENV severity. Herein, we investigated the potential of quantitative thrombocyte function tests in those admitted in the very early phase of acute DENV infections, using Multiplate™ multiple-electrode aggregometry to explore its potential in triage. METHODS: In this prospective cohort study all patients aged ≥13 admitted to Universitas Airlangga Hospital in Surabaya, Indonesia with a fever (≥38 °C) between 25 January and 1 August 2018 and with a clinical suspicion of DENV, were eligible for inclusion. Exclusion criteria were a thrombocyte count below 100 × 109/L and the use of any medication with a known anticoagulant effect, nonsteroidal anti-inflammatory drugs and acetyl salicylic acid. Clinical data was collected and blood was taken on admission, day 1 and day 7. Samples were tested for acute DENV, using Panbio NS1 ELISA. Platelet aggregation using ADP-, TRAP- and COL-test were presented as Area Under the aggregation Curve (AUC). Significance was tested between DENV+, probably DENV, fever of another origin, and healthy controls (HC). RESULTS: A total of 59 patients (DENV+ n = 10, DENV probable n = 25, fever other origin n = 24) and 20 HC were included. We found a significantly lower thrombocyte aggregation in the DENV+ group, compared with both HCs and the fever of another origin group (p < .001). Low ADP AUC values on baseline correlated to a longer hospital stay in DENV+ and probable DENV cases. CONCLUSION: Thrombocyte aggregation induced by Adenosine diphosphate, Collagen and Thrombin receptor activating peptide-6 is impaired in human DENV cases, compared with healthy controls and other causes of fever. This explorative study provides insights to thrombocyte function in DENV patients and could potentially serve as a future marker in DENV disease.


Assuntos
Plaquetas/metabolismo , Vírus da Dengue/imunologia , Dengue/diagnóstico , Dengue/epidemiologia , Sistemas Automatizados de Assistência Junto ao Leito , Testes Imediatos , Difosfato de Adenosina/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Colágeno/metabolismo , Dengue/virologia , Ensaio de Imunoadsorção Enzimática , Feminino , Febre/diagnóstico , Humanos , Indonésia/epidemiologia , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Agregação Plaquetária , Contagem de Plaquetas , Estudos Prospectivos , Índice de Gravidade de Doença , Adulto Jovem
8.
PLoS One ; 15(8): e0237141, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764789

RESUMO

Severe dengue can be lethal caused by manifestations such as severe bleeding, fluid accumulation and organ impairment. This study aimed to investigate the role of dengue non-structural 1 (NS1) protein and host factors contributing to severe dengue. Electrical cell-substrate impedance sensing system was used to investigate the changes in barrier function of microvascular endothelial cells treated NS1 protein and serum samples from patients with different disease severity. Cytokines and metabolites profiles were assessed using a multiplex cytokine assay and liquid chromatography mass spectrometry respectively. The findings showed that NS1 was able to induce the loss of barrier function in microvascular endothelium in a dose dependent manner, however, the level of NS1 in serum samples did not correlate with the extent of vascular leakage induced. Further assessment of host factors revealed that cytokines such as CCL2, CCL5, CCL20 and CXCL1, as well as adhesion molecule ICAM-1, that are involved in leukocytes infiltration were expressed higher in dengue patients in comparison to healthy individuals. In addition, metabolomics study revealed the presence of deregulated metabolites involved in the phospholipid metabolism pathway in patients with severe manifestations. In conclusion, disease severity in dengue virus infection did not correlate directly with NS1 level, but instead with host factors that are involved in the regulation of junctional integrity and phospholipid metabolism. However, as the studied population was relatively small in this study, these exploratory findings should be confirmed by expanding the sample size using an independent cohort to further establish the significance of this study.


Assuntos
Citocinas/sangue , Vírus da Dengue/imunologia , Interações Hospedeiro-Patógeno/imunologia , Dengue Grave/sangue , Proteínas não Estruturais Virais/sangue , Linhagem Celular , Citocinas/imunologia , Citocinas/metabolismo , Vírus da Dengue/metabolismo , Células Endoteliais/imunologia , Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/imunologia , Endotélio Vascular/patologia , Humanos , Fosfolipídeos/metabolismo , Cultura Primária de Células , Dengue Grave/imunologia , Dengue Grave/metabolismo , Dengue Grave/patologia , Proteínas não Estruturais Virais/imunologia
9.
Nat Rev Immunol ; 20(10): 633-643, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32782358

RESUMO

Antibody-dependent enhancement (ADE) is a mechanism by which the pathogenesis of certain viral infections is enhanced in the presence of sub-neutralizing or cross-reactive non-neutralizing antiviral antibodies. In vitro modelling of ADE has attributed enhanced pathogenesis to Fcγ receptor (FcγR)-mediated viral entry, rather than canonical viral receptor-mediated entry. However, the putative FcγR-dependent mechanisms of ADE overlap with the role of these receptors in mediating antiviral protection in various viral infections, necessitating a detailed understanding of how this diverse family of receptors functions in protection and pathogenesis. Here, we discuss the diversity of immune responses mediated upon FcγR engagement and review the available experimental evidence supporting the role of FcγRs in antiviral protection and pathogenesis through ADE. We explore FcγR engagement in the context of a range of different viral infections, including dengue virus and SARS-CoV, and consider ADE in the context of the ongoing SARS-CoV-2 pandemic.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos Antivirais/administração & dosagem , Anticorpos Facilitadores/efeitos dos fármacos , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Leucócitos/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Receptores de IgG/imunologia , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/biossíntese , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/efeitos adversos , Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/efeitos adversos , Anticorpos Antivirais/biossíntese , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Dengue/tratamento farmacológico , Dengue/imunologia , Dengue/virologia , Vírus da Dengue/efeitos dos fármacos , Vírus da Dengue/imunologia , Vírus da Dengue/patogenicidade , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Leucócitos/imunologia , Leucócitos/virologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Receptores de IgG/antagonistas & inibidores , Receptores de IgG/genética , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/imunologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Transdução de Sinais , Internalização do Vírus/efeitos dos fármacos
10.
BMC Infect Dis ; 20(1): 466, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32615988

RESUMO

BACKGROUND: Dengue fever is a major public health problem in Colombia. A fever surveillance study was conducted for evaluation of the clinical, epidemiological, and molecular patterns of dengue, prior to Chikungunya and Zika epidemics. METHODS: In November 2011-February 2014, a passive facility-based surveillance was implemented in Santa Cruz Hospital, Medellin, and enrolled eligible febrile patients between 1 and 65 years-of-age. Acute and convalescent blood samples were collected 10-21 days apart and tested for dengue using IgM/IgG ELISA. RNA was extracted for serotyping using RT-PCR on acute samples and genotyping was performed by sequencing. RESULTS: Among 537 febrile patients enrolled during the study period, 29% (n = 155) were identified to be dengue-positive. Only 7% of dengue cases were hospitalized, but dengue-positive patients were 2.6 times more likely to be hospitalized, compared to non-dengue cases, based on a logistic regression. From those tested with RT-PCR (n = 173), 17 were dengue-confirmed based on PCR and/or virus isolation showing mostly DENV-3 (n = 9) and DENV-4 (n = 7) with 1 DENV-1. Genotyping results showed that: DENV-1 isolate belongs to the genotype V or American/African genotype; DENV-3 isolates belong to genotype III; and DENV-4 isolates belong to the II genotype and specifically to the IIb sub-genotype or linage. CONCLUSIONS: Our surveillance documented considerable dengue burden in Santa Cruz comuna during non-epidemic years, and genetic diversity of circulating DENV isolates, captured prior to Chikungunya epidemic in 2014 and Zika epidemic in 2015. Our study findings underscore the need for continued surveillance and monitoring of dengue and other arboviruses and serve as epidemiological and molecular evidence base for future studies to assess changes in DENV transmission in Medellin, given emerging and re-emerging arboviral diseases in the region.


Assuntos
Vírus da Dengue/genética , Vírus da Dengue/imunologia , Dengue/epidemiologia , Febre/epidemiologia , Variação Genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Colômbia/epidemiologia , Dengue/virologia , Vírus da Dengue/isolamento & purificação , Doenças Endêmicas , Ensaio de Imunoadsorção Enzimática , Feminino , Febre/virologia , Genótipo , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
11.
PLoS Negl Trop Dis ; 14(7): e0008061, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32687540

RESUMO

Tanzania has recently experienced outbreaks of dengue in two coastal regions of Dar es Salaam and Tanga. Chikungunya and Rift Valley Fever outbreaks have also been recorded in the past decade. Little is known on the burden of the arboviral disease causing viruses (Dengue, Rift Valley and Chikungunya) endemically in the inter-epidemic periods. We aimed at determining the prevalence of the dengue, rift valley and chikungunya among humans in two geo ecologically distinct sites. The community-based cross-sectional study was conducted in Magugu in Manyara region and Wami-Dakawa in Morogoro region in Tanzania. Venous blood was collected from participants of all age groups, serum prepared from samples and subjected to ELISA tests for RVFV IgG/IgM, DENV IgG/IgM, and CHIKV IgM/IgG. Samples that were positive for IgM ELISA tests were subjected to a quantitative RT PCR for each virus. A structured questionnaire was used to collect socio-demographic information. Data analysis was performed by using SPSSv22. A total of 191 individuals from both sites participated in the study. Only one individual was CHIKV seropositive in Magugu, but none was seropositive or positive for either RVFV or DENV. Of the 122 individuals from Wami-Dakawa site, 16.39% (n = 20) had recent exposure to RVFV while 9.83% (n = 12) were seropositive for CHIKV. All samples were negative by RVFV and CHIKV qPCR. Neither infection nor exposure to DENV was observed in participants from both sites. Being more than 5 in a household, having no formal education and having recently travelled to an urban area were risk factors associated with RVFV and CHIKV seropositivity. We report a considerable exposure to RVFV and CHIKV among Wami-Dakawa residents during the dry season and an absence of exposure of the viruses among humans in Magugu site. In both sites, neither DENV exposure nor infection was detected.


Assuntos
Anticorpos Antivirais/sangue , Febre de Chikungunya/sangue , Vírus Chikungunya/imunologia , Vírus da Dengue/imunologia , Dengue/sangue , Febre do Vale de Rift/sangue , Vírus da Febre do Vale do Rift/imunologia , Adulto , Animais , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/virologia , Vírus Chikungunya/fisiologia , Estudos Transversais , Dengue/epidemiologia , Dengue/virologia , Vírus da Dengue/fisiologia , Feminino , Humanos , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Febre do Vale de Rift/epidemiologia , Febre do Vale de Rift/virologia , Vírus da Febre do Vale do Rift/fisiologia , Estudos Soroepidemiológicos , Tanzânia/epidemiologia , Adulto Jovem
12.
Nature ; 584(7821): 353-363, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32659783

RESUMO

Antibody-dependent enhancement (ADE) of disease is a general concern for the development of vaccines and antibody therapies because the mechanisms that underlie antibody protection against any virus have a theoretical potential to amplify the infection or trigger harmful immunopathology. This possibility requires careful consideration at this critical point in the pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we review observations relevant to the risks of ADE of disease, and their potential implications for SARS-CoV-2 infection. At present, there are no known clinical findings, immunological assays or biomarkers that can differentiate any severe viral infection from immune-enhanced disease, whether by measuring antibodies, T cells or intrinsic host responses. In vitro systems and animal models do not predict the risk of ADE of disease, in part because protective and potentially detrimental antibody-mediated mechanisms are the same and designing animal models depends on understanding how antiviral host responses may become harmful in humans. The implications of our lack of knowledge are twofold. First, comprehensive studies are urgently needed to define clinical correlates of protective immunity against SARS-CoV-2. Second, because ADE of disease cannot be reliably predicted after either vaccination or treatment with antibodies-regardless of what virus is the causative agent-it will be essential to depend on careful analysis of safety in humans as immune interventions for COVID-19 move forward.


Assuntos
Anticorpos Antivirais/efeitos adversos , Anticorpos Antivirais/imunologia , Anticorpos Facilitadores/imunologia , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Animais , Anticorpos Neutralizantes/efeitos adversos , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , Infecções por Coronavirus/prevenção & controle , Vírus da Dengue/imunologia , Modelos Animais de Doenças , Células HEK293 , Humanos , Fragmentos Fab das Imunoglobulinas/imunologia , Fragmentos Fc das Imunoglobulinas/imunologia , Imunoglobulina G/imunologia , Macaca mulatta , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Orthomyxoviridae/imunologia , Pandemias , Ratos , Vírus da SARS/imunologia , Vacinas Virais/efeitos adversos , Vacinas Virais/imunologia
13.
Nat Commun ; 11(1): 3112, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32561757

RESUMO

Previous flavivirus (dengue and Zika viruses) studies showed largely spherical particles either with smooth or bumpy surfaces. Here, we demonstrate flavivirus particles have high structural plasticity by the induction of a non-spherical morphology at elevated temperatures: the club-shaped particle (clubSP), which contains a cylindrical tail and a disc-like head. Complex formation of DENV and ZIKV with Fab C10 stabilize the viruses allowing cryoEM structural determination to ~10 Å resolution. The caterpillar-shaped (catSP) Fab C10:ZIKV complex shows Fabs locking the E protein raft structure containing three E dimers. However, compared to the original spherical structure, the rafts have rotated relative to each other. The helical tail structure of Fab C10:DENV3 clubSP showed although the Fab locked an E protein dimer, the dimers have shifted laterally. Morphological diversity, including clubSP and the previously identified bumpy and smooth-surfaced spherical particles, may help flavivirus survival and immune evasion.


Assuntos
Anticorpos Antivirais/metabolismo , Vírus da Dengue/ultraestrutura , Proteínas do Envelope Viral/metabolismo , Zika virus/ultraestrutura , Aedes , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/metabolismo , Anticorpos Antivirais/imunologia , Linhagem Celular , Microscopia Crioeletrônica , Dengue/imunologia , Dengue/terapia , Dengue/virologia , Vacinas contra Dengue/imunologia , Vírus da Dengue/imunologia , Vírus da Dengue/metabolismo , Evasão da Resposta Imune , Fragmentos Fab das Imunoglobulinas/imunologia , Fragmentos Fab das Imunoglobulinas/metabolismo , Mesocricetus , Multimerização Proteica , Propriedades de Superfície , Proteínas do Envelope Viral/imunologia , Proteínas do Envelope Viral/ultraestrutura , Ligação Viral , Zika virus/imunologia , Zika virus/metabolismo , Infecção por Zika virus
14.
Cytometry A ; 97(7): 662-667, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32506725

RESUMO

SARS-CoV-2 pandemic and recurrent dengue epidemics in tropical countries have turned into a global health threat. While both virus-caused infections may only reveal light symptoms, they can also cause severe diseases. Here, we review the possible antibody-dependent enhancement (ADE) occurrence, known for dengue infections, when there is a second infection with a different virus strain. Consequently, preexisting antibodies do not neutralize infection, but enhance it, possibly by triggering Fcγ receptor-mediated virus uptake. No clinical data exist indicating such mechanism for SARS-CoV-2, but previous coronavirus infections or infection of SARS-CoV-2 convalescent with different SARS-CoV-2 strains could promote ADE, as experimentally shown for antibodies against the MERS-CoV or SARS-CoV spike S protein. © 2020 International Society for Advancement of Cytometry.


Assuntos
Anticorpos Facilitadores/imunologia , Betacoronavirus/imunologia , Coinfecção/imunologia , Vírus da Dengue/imunologia , Receptores de IgG/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Dengue/imunologia , Dengue/patologia , Humanos , Citometria por Imagem/métodos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Vírus da SARS/imunologia , Internalização do Vírus
15.
Artigo em Inglês | MEDLINE | ID: mdl-32407701

RESUMO

In this issue of Cell Host & Microbe, Young et al. shed light on dengue virus 3-specific epitopes. Mapping of human monoclonal antibodies led to the discovery of six quaternary antigenic sites with strong neutralizing activity suggesting that epitopes involved with protective immunity may be more complex than previously realized.


Assuntos
Anticorpos Neutralizantes , Vírus da Dengue/imunologia , Anticorpos Antivirais , Epitopos , Humanos , Sorogrupo
16.
Am J Trop Med Hyg ; 103(1): 112-119, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32431270

RESUMO

This study describes the natural history of dengue virus (DENV) infection in rhesus monkeys exposed to the bites of DENV-infected Aedes aegypti mosquitoes. Dengue virus-infected mosquitoes were generated by either intrathoracic inoculation or by oral feeding on viremic blood meals. Each of the six rhesus monkeys that were fed upon by intrathoracically infected mosquitoes developed non-structural protein 1 (NS1) antigenemia and an IgM response; viremia was detected in 4/6 individuals. No virological or immunological evidence of DENV infection was detected in the three monkeys exposed to mosquitoes that had been orally infected with DENV. These results demonstrate the utility of mosquito-borne challenge of rhesus monkeys with DENV.


Assuntos
Aedes/virologia , Anticorpos Antivirais/sangue , Vírus da Dengue/imunologia , Dengue/imunologia , Imunoglobulina M/sangue , Mosquitos Vetores/virologia , Viremia/imunologia , Animais , Dengue/sangue , Dengue/diagnóstico , Dengue/transmissão , Vírus da Dengue/genética , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Macaca mulatta , Projetos Piloto , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas não Estruturais Virais/genética , Viremia/sangue , Viremia/diagnóstico , Viremia/transmissão
17.
BMC Infect Dis ; 20(1): 335, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398134

RESUMO

BACKGROUND: Dengue fever is a hemorrhagic fever caused by flaviviruses. Hemorrhagic manifestations are well known to be associated with dengue fever, though the thrombotic events are only seldom reported. Underlying pathophysiology of thrombotic events is multifactorial and the management is challenging due to associated thrombocytopenia and bleeding tendency. We report a case of dengue shock syndrome with severe thrombocytopenia complicated by ilio-femoral deep vein thrombosis. CASE PRESENTATION: A 16 year old boy presented with dengue fever. He had dengue shock syndrome after entering the critical phase on the fifth day of the illness. With the recovery from the critical phase he developed deep vein thrombosis involving right external iliac, common femoral and superficial femoral veins. There were no provocative factors other than dengue fever itself. His platelet count was 12,000/µl at the time of diagnosis with deep vein thrombosis. Anticoagulation was started with intravenous unfractionated heparin 500 IU/hour while closely being observed for bleeding complications. 1000 IU/hour dose was commenced with the recovery of the platelet count above 50,000/µl. Thrombophilia screening was negative and he was discharged on warfarin. Venous duplex done after 6 weeks showed normal lower limb venous flow and warfarin was omitted after three months. CONCLUSIONS: With dengue fever, complications like deep vein thrombosis can be easily missed given its rarity and that the major concern is on hemorrhagic complications. Management is challenging due to associated thrombocytopenia and hemorrhagic complications.


Assuntos
Vírus da Dengue/imunologia , Veia Femoral/patologia , Extremidade Inferior/irrigação sanguínea , Dengue Grave/complicações , Trombocitopenia/complicações , Trombose Venosa/etiologia , Administração Intravenosa , Adolescente , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Antígenos Virais/análise , Heparina/administração & dosagem , Heparina/uso terapêutico , Humanos , Masculino , Resultado do Tratamento , Trombose Venosa/tratamento farmacológico , Varfarina/uso terapêutico
18.
BMC Infect Dis ; 20(1): 332, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393198

RESUMO

BACKGROUND: Between 2016 and 2019, 265 cases of Zika virus (ZIKV) infection were reported in Vietnam, predominantly in southern Vietnam. In 2016, a case of ZIKV-associated microcephaly was confirmed in the Central Highlands, and several members of the infant's family were confirmed to be infected with ZIKV. The study aims to determine the level of immunity to ZIKV in the general population of the ZIKV epidemic region. METHODS: A total of 879 serum samples were collected from 801 participants between January 2017 and July 2018, during and after the ZIKV epidemic in Vietnam. The samples were tested for anti-ZIKV immunoglobulin M (IgM) and immunoglobulin G (IgG), and anti-dengue virus (DENV) IgG antibodies using enzyme-linked immunosorbent assays (ELISA). Plaque-reduction neutralization test (PRNT) for ZIKV was performed on all samples, and for DENV on the samples that ZIKV neutralizing antibody positive. RESULTS: A total of 83 (10.3%) participants had anti-ZIKV IgM. Of the 83, 6 were confirmed to be ZIKV antibodies positive using PRNT and anti-ZIKV IgG ELISA. Of the 718 participants who were anti-ZIKV IgM negative, a further 3 cases were confirmed as positive for antibodies against ZIKV. Of the 9 participants with ZIKV infection, 5 lived in the same village as the infant with ZIKV-associated microcephaly and the other 4 lived in 2 neighboring communes. Repeat samples were collected from the 83 ZIKV IgM positive participants 1.5 years after the first collection. No new cases of ZIKV infection were detected. In addition, 2 of 3 participants with anti-ZIKV NS1 IgG demonstrated a 4- to 8-fold increase in ZIKV neutralizing antibody titer. CONCLUSIONS: ZIKV was present in the area around Krong Buk, with the rate of ZIKV-specific antibodies was 1.1% in the community since at least 2016. While the low levels of circulation together with low seroprevalence suggests a limited outbreak in the region, the results also reflect on low levels of protective immunity to Zika within the population. These results provide a better understanding of the current ZIKV epidemic status in the region and demonstrate a need for implementation of more effective ZIKV infection control measures.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Epidemias , Infecção por Zika virus/epidemiologia , Zika virus/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Vírus da Dengue/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Microcefalia/virologia , Pessoa de Meia-Idade , Testes de Neutralização , Prevalência , Estudos Soroepidemiológicos , Vietnã/epidemiologia , Adulto Jovem , Infecção por Zika virus/virologia
19.
Am J Trop Med Hyg ; 103(1): 142-148, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32314687

RESUMO

We estimated the incidence of laboratory-confirmed dengue patients for Surat city, India, using surveillance data from 2011 to 2016 and described the related entomological indices and climatic factors. There was a rise in incidence from 1.5 to 17.6 per 100,000 population, as the numbers of notified cases have increased because of better surveillance system. The case notification was 1.3 times higher for the public sector than the private sector. The larval indices were below the transmission level (House index, Breteau index < 1%). The median age of dengue patients was 20 years (IQR: 14-28), with a male to female ratio of 1.6:1. Five peripheral vector control units contributed to 1,013 (41.4%) confirmed cases with rising incidence in other units also. The number of dengue patients peaked during post-monsoon. Spearman's correlation of vector density with humidity (r s = 0.556), rainfall (r s = 0.644), and number of cases (r s = 0.708) suggested climate favorable for vector breeding. There is a good system of public-private coordination for dengue surveillance. However, there is a need to reassess the vector indices threshold for transmission in the city.


Assuntos
Aedes/virologia , Anticorpos Antivirais/sangue , Dengue/epidemiologia , Imunoglobulina M/sangue , Larva/virologia , Mosquitos Vetores/virologia , Adolescente , Adulto , Animais , Criança , Pré-Escolar , Clima , Dengue/diagnóstico , Dengue/imunologia , Dengue/virologia , Vírus da Dengue/genética , Vírus da Dengue/imunologia , Vírus da Dengue/patogenicidade , Notificação de Doenças/estatística & dados numéricos , Monitoramento Epidemiológico , Feminino , Humanos , Umidade , Incidência , Índia/epidemiologia , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Parcerias Público-Privadas , Proteínas não Estruturais Virais/genética
20.
Am J Trop Med Hyg ; 103(1): 100-111, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32342838

RESUMO

Dengue is endemic in Brazil. The dengue surveillance system's reliance on passive reporting may underestimate disease incidence and cannot detect asymptomatic/pauci-symptomatic cases. In this 3-year prospective cohort study (NCT01391819) in 5- to 13-year-old children from nine schools in Fortaleza (N = 2,117), we assessed dengue virus (DENV) infection seroprevalence by IgG indirect ELISA at yearly visits and disease incidence through active and enhanced passive surveillance. Real-time quantitative polymerase chain reaction (RT-qPCR) and DENV IgM/IgG capture ELISA were used for diagnosis. We further characterized confirmed and probable cases with a plaque reduction neutralization test. At enrollment, 54.1% (95% CI: 46.6, 61.4) of children were DENV IgG positive. The annual incidence of laboratory-confirmed symptomatic dengue cases was 11.0 (95% CI: 7.3, 14.7), 18.1 (10.4, 25.7), and 10.2 (0.7, 19.7), and of laboratory-confirmed or probable dengue cases with neutralizing antibody profile evocative of dengue exposure was 13.2 (6.6, 19.9), 18.7 (5.3, 32.2), and 8.4 (2.4, 19.2) per 1,000 child-years in 2012, 2013, and 2014, respectively. By RT-qPCR, we identified 14 DENV-4 cases in 2012-2013 and seven DENV-1 cases in 2014. During the course of the study, 32.8% of dengue-naive children experienced a primary infection. Primary inapparent dengue infection was detected in 20.3% (95% CI: 13.6, 29.1) of dengue-naive children in 2012, 8.7% (6.9, 10.9) in 2013, and 5.1% (4.4, 6.0) in 2014. Our results confirmed the high dengue endemicity in Fortaleza, with active and enhanced passive surveillance detecting three to five times more cases than the National System of Disease Notification.


Assuntos
Anticorpos Antivirais/sangue , Vírus da Dengue/imunologia , Dengue/epidemiologia , Imunoglobulina G/sangue , Adolescente , Infecções Assintomáticas , Brasil/epidemiologia , Criança , Pré-Escolar , Dengue/diagnóstico , Dengue/imunologia , Dengue/virologia , Vírus da Dengue/classificação , Vírus da Dengue/genética , Notificação de Doenças/estatística & dados numéricos , Monitoramento Epidemiológico , Feminino , Humanos , Incidência , Masculino , Testes de Neutralização , Estudos Prospectivos , Estudos Soroepidemiológicos , Índice de Gravidade de Doença
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