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1.
Virol J ; 18(1): 54, 2021 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-33706767

RESUMEN

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic remains ongoing around the world, including in areas where dengue is endemic. Dengue and COVID-19, to some extent, have similar clinical and laboratory features, which can lead to misdiagnosis, delayed treatment and patient's isolation. The use of rapid diagnostic tests (RDT) is easy and convenient for fast diagnosis, however there may be issues with cross-reactivity with antibodies for other pathogens. METHODS: We assessed the possibility of cross-reactivity between SARS-CoV-2 and dengue antibodies by: (1) testing five brands of COVID-19 IgG / IgM RDTs on 60 RT-PCR-confirmed dengue samples; (2) testing 95 RT-PCR-confirmed COVID-19 samples on dengue RDT; and (3) testing samples positive for COVID-19 IgG and/or IgM on dengue RDT. RESULTS: We observed a high specificity across all five brands of COVID-19 RDTs, ranging from 98.3 to 100%. Out of the confirmed COVID-19 samples, one patient tested positive for dengue IgM only, another tested positive for dengue IgG only. One patient tested positive for dengue IgG, IgM, and NS1, suggesting a co-infection. In COVID-19 IgG and/or IgM samples, 6.3% of COVID-19 IgG-positive samples also tested positive for dengue IgG, while 21.1% of COVID-19 IgM-positive samples also tested positive for dengue IgG. CONCLUSION: Despite the high specificity of the COVID-19 RDT, we observed cross-reactions and false-positive results between dengue and COVID-19. Dengue and COVID-19 co-infection was also found. Health practitioners in dengue endemic areas should be careful when using antibody RDT for the diagnosis of dengue during the COVID-19 pandemic to avoid misdiagnosis.


Asunto(s)
Anticuerpos Antivirales/inmunología , Reacciones Cruzadas/inmunología , Virus del Dengue/inmunología , Dengue/diagnóstico , /inmunología , Adolescente , Adulto , Niño , Diagnóstico Diferencial , Pruebas Diagnósticas de Rutina , Reacciones Falso Positivas , Femenino , Humanos , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Indonesia , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Proteínas no Estructurales Virales/inmunología , Adulto Joven
2.
Mem Inst Oswaldo Cruz ; 115: e200287, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33533869

RESUMEN

BACKGROUND: The heat-labile nature of Dengue virus (DENV) in serum samples must be considered when applying routine diagnostic tests to avoid issues that could impact the accuracy of test results with direct implications for case management and disease reporting. OBJECTIVES: To check if pre-analytical variables, such as storage time and temperature, have an impact on the accuracy of the main routine diagnostic tests for dengue. METHODS: Virus isolation, reverse transcription real-time polymerase chain reaction (RT-PCR) and NS1 enzyme-linked immunosorbent assay (ELISA) were evaluated using 84 samples submitted to different pre-analytical conditions. FINDINGS: Sensitivity and negative predictive value were directly affected by sample storage conditions. RT-PCR and virus isolation showed greater dependence on well-conserved samples for an accurate diagnosis. Interestingly, even storage at -30ºC for a relatively short time (15 days) was not adequate for accurate results using virus isolation and RT-PCR tests. On the other hand, NS1 ELISA showed no significant reduction in positivity for aliquots tested under the same conditions as in the previous tests. MAIN CONCLUSIONS: Our results support the stability of the NS1 marker in ELISA diagnosis and indicate that the accuracy of routine tests such as virus isolation and RT-PCR is significantly affected by inadequate transport and storage conditions of serum samples.


Asunto(s)
Antígenos Virales/sangre , Virus del Dengue/aislamiento & purificación , Dengue/diagnóstico , Ensayo de Inmunoadsorción Enzimática/métodos , Pruebas Inmunológicas/métodos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Proteínas no Estructurales Virales/inmunología , Anticuerpos Antivirales/sangre , Antígenos Virales/inmunología , Dengue/sangre , Dengue/virología , Virus del Dengue/genética , Virus del Dengue/inmunología , Humanos , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Proteínas no Estructurales Virales/genética
3.
Nat Commun ; 12(1): 1102, 2021 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-33597521

RESUMEN

The four-dengue virus (DENV) serotypes infect several hundred million people annually. For the greatest safety and efficacy, tetravalent DENV vaccines are designed to stimulate balanced protective immunity to all four serotypes. However, this has been difficult to achieve. Clinical trials with a leading vaccine demonstrated that unbalanced replication and immunodominance of one vaccine component over others can lead to low efficacy and vaccine enhanced severe disease. The Laboratory of Infectious Diseases at the National Institutes of Health has developed a live attenuated tetravalent DENV vaccine (TV003), which is currently being tested in phase 3 clinical trials. Here we report, our study to determine if TV003 stimulate balanced and serotype-specific (TS) neutralizing antibody (nAb) responses to each serotype. Serum samples from twenty-one dengue-naive individuals participated under study protocol CIR287 (ClinicalTrials.gov NCT02021968) are analyzed 6 months after vaccination. Most subjects (76%) develop TS nAbs to 3 or 4 DENV serotypes, indicating immunity is induced by each vaccine component. Vaccine-induced TS nAbs map to epitopes known to be targets of nAbs in people infected with wild type DENVs. Following challenge with a partially attenuated strain of DENV2, all 21 subjects are protected from the efficacy endpoints. However, some vaccinated individuals develop post challenge nAb boost, while others mount post-challenge antibody responses that are consistent with sterilizing immunity. TV003 vaccine induced DENV2 TS nAbs are associated with sterilizing immunity. Our results indicate that nAbs to TS epitopes on each serotype may be a better correlate than total levels of nAbs currently used for guiding DENV vaccine development.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Vacunas contra el Dengue/inmunología , Virus del Dengue/inmunología , Dengue/inmunología , Formación de Anticuerpos/inmunología , Especificidad de Anticuerpos/inmunología , Dengue/prevención & control , Dengue/virología , Vacunas contra el Dengue/administración & dosificación , Virus del Dengue/clasificación , Epítopos/inmunología , Humanos , Serotipificación , Especificidad de la Especie , Resultado del Tratamiento , Vacunación/métodos , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/inmunología
4.
Science ; 371(6525): 190-194, 2021 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-33414219

RESUMEN

There are no approved flaviviral therapies and the development of vaccines against flaviruses has the potential of being undermined by antibody-dependent enhancement (ADE). The flavivirus nonstructural protein 1 (NS1) is a promising vaccine antigen with low ADE risk but has yet to be explored as a broad-spectrum therapeutic antibody target. Here, we provide the structural basis of NS1 antibody cross-reactivity through cocrystallization of the antibody 1G5.3 with NS1 proteins from dengue and Zika viruses. The 1G5.3 antibody blocks multi-flavivirus NS1-mediated cell permeability in disease-relevant cell lines, and therapeutic application of 1G5.3 reduces viremia and improves survival in dengue, Zika, and West Nile virus murine models. Finally, we demonstrate that 1G5.3 protection is independent of effector function, identifying the 1G5.3 epitope as a key site for broad-spectrum antiviral development.


Asunto(s)
Anticuerpos Neutralizantes/química , Anticuerpos Antivirales/química , Virus del Dengue/inmunología , Proteínas no Estructurales Virales/inmunología , Virus del Nilo Occidental/inmunología , Virus Zika/inmunología , Animales , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/uso terapéutico , Células CHO , Línea Celular , Cricetulus , Reacciones Cruzadas , Dengue/prevención & control , Dengue/terapia , Modelos Animales de Enfermedad , Humanos , Ratones , Dominios Proteicos , Proteínas no Estructurales Virales/química , Viremia/terapia , Fiebre del Nilo Occidental/prevención & control , Fiebre del Nilo Occidental/terapia , Infección por el Virus Zika/prevención & control , Infección por el Virus Zika/terapia
5.
BMC Infect Dis ; 21(1): 96, 2021 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-33478432

RESUMEN

BACKGROUND: Dengue virus infection has been an important and serious public health concern in Taiwan, where local outbreaks of dengue fever occurred almost every year. To our knowledge, no nationwide investigation has been carried out to determine the actual extent of infection in the general population. METHODS: A total of 1308 random serum samples were collected from the general population in Taiwan in 2010. The antibody-captured enzyme-linked immunosorbent assays were used to detect DENV-specific IgM and IgG. Demographics data were used for risk analysis. RESULTS: The weighted overall seroprevalence was 1.96% for anti-DENV IgM, and 3.4% for anti-DENV IgG, respectively. A significant rise of DENV IgG seropositive rate had been noted since late adulthood stage, from 1.1% at the age group of 50-59 years to 7.6% at the age group of 60-69 years. For people aged over 70 years, the seropositive rate reached 19%. Age, nationality, and regions of residency were associated with the IgG seropositivity. There was no statistically significant difference in seroprevalence of anti-Dengue IgM, indicating recent infection, among univariate predictors we proposed, including gender, age, residency, nationality, and household size. CONCLUSIONS: Our results indicated that the majority of population in Taiwan born after 1940 is naive to dengue virus and the prevalence of IgG antibody against dengue virus rises with age. Nationality, and regions of residency are associated with the exposure of population to infection by dengue viruses. Further studies are needed to realize the current situation of seroprevalence of dengue fever in Taiwan.


Asunto(s)
Anticuerpos Antivirales/sangre , Virus del Dengue/inmunología , Dengue/epidemiología , Adolescente , Adulto , Anciano , Niño , Preescolar , Dengue/sangre , Virus del Dengue/aislamiento & purificación , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Estudios Seroepidemiológicos , Taiwán/epidemiología , Adulto Joven
6.
BMC Infect Dis ; 21(1): 104, 2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33482756

RESUMEN

BACKGROUND: Dengue virus (DENV) infection is increasingly common in southern China and can be transmitted through blood transfusion but is not currently part of donor screening throughout the region. We assessed DENV prevalence among donors at the Xishuangbanna Blood Center, Yunnan, to support development of DENV screening strategies. METHODS: Blood samples were collected randomly between June 2019 and August 2019. These were screened for anti-DENV IgG and IgM using enzyme-linked immunosorbent assay (ELISA). Then, all reactive samples and some randomly-chosen non-reactive samples were used to detect DENV RNAs using real-time polymerase-chain-reaction (RT-PCR) assays. After RT-PCR, samples were further tested for soluble nonstructural protein 1 (NS1) using the colloidal gold method. Donors demographics were also collected and assessed. RESULTS: Over the study period, 2254 donor samples were collected and tested for anti-DENV IgG and IgM by ELISA. This revealed 598 anti-DENV IgG and/or IgM reactive samples, a serological prevalence of 26.53%. Of these, 26 were RT-PCR positive and/or NS1 positive. Significant differences in DENV prevalence were noted by occupation (P = 0.001), education (P < 0.001), and ethnicity (P = 0.026). CONCLUSION: The prevalence of DENV in Xishuangbanna Blood Center was higher than most other blood centers that have implemented DENV donor screening. Our study provides first-hand data about the prevalence of DENV and allows the development of a screening strategy for clinical use.


Asunto(s)
Donantes de Sangre , Virus del Dengue/aislamiento & purificación , Dengue/diagnóstico , Dengue/epidemiología , Tamizaje Masivo/métodos , Adulto , Anticuerpos Antivirales/sangre , China/epidemiología , Dengue/sangre , Virus del Dengue/genética , Virus del Dengue/inmunología , Femenino , Humanos , Masculino , Tamizaje Masivo/estadística & datos numéricos , Persona de Mediana Edad , Prevalencia , ARN Viral/genética , Proteínas no Estructurales Virales/genética , Adulto Joven
7.
Science ; 371(6525): 194-200, 2021 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-33414220

RESUMEN

Medically important flaviviruses cause diverse disease pathologies and collectively are responsible for a major global disease burden. A contributing factor to pathogenesis is secreted flavivirus nonstructural protein 1 (NS1). Despite demonstrated protection by NS1-specific antibodies against lethal flavivirus challenge, the structural and mechanistic basis remains unknown. Here, we present three crystal structures of full-length dengue virus NS1 complexed with a flavivirus-cross-reactive, NS1-specific monoclonal antibody, 2B7, at resolutions between 2.89 and 3.96 angstroms. These structures reveal a protective mechanism by which two domains of NS1 are antagonized simultaneously. The NS1 wing domain mediates cell binding, whereas the ß-ladder triggers downstream events, both of which are required for dengue, Zika, and West Nile virus NS1-mediated endothelial dysfunction. These observations provide a mechanistic explanation for 2B7 protection against NS1-induced pathology and demonstrate the potential of one antibody to treat infections by multiple flaviviruses.


Asunto(s)
Anticuerpos Neutralizantes/química , Anticuerpos Antivirales/química , Virus del Dengue/inmunología , Proteínas no Estructurales Virales/inmunología , Virus del Nilo Occidental/inmunología , Virus Zika/inmunología , Animales , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Reacciones Cruzadas , Cristalografía por Rayos X , Dengue/prevención & control , Dengue/terapia , Endotelio/inmunología , Glicocálix/inmunología , Humanos , Ratones , Conformación Proteica en Lámina beta , Dominios Proteicos , Proteínas no Estructurales Virales/química , Fiebre del Nilo Occidental/prevención & control , Fiebre del Nilo Occidental/terapia , Infección por el Virus Zika/prevención & control , Infección por el Virus Zika/terapia
8.
BMC Infect Dis ; 20(1): 948, 2020 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-33308178

RESUMEN

BACKGROUND: Dengue patients develop different disease severity ranging from mild (dengue fever [DF]) to severe forms (dengue hemorrhagic fever [DHF] and the fatal dengue shock syndrome [DSS]). Host genetics are considered to be one factor responsible for the severity of dengue outcomes. To identify genes associated with dengue severity that have not been studied yet, we performed genetic association analyses of interferon lambda 3 (IFNL3), CD27, and human leukocyte antigen-DPB1 (HLA-DPB1) genes in Thai dengue patients. METHODS: A case-control association study was performed in 877 children (age ≤ 15 years) with dengue infection (DF, n = 386; DHF, n = 416; DSS, n = 75). A candidate single nucleotide polymorphism of each of IFNL3, CD27, and HLA-DPB1 was selected to be analyzed. Genotyping was performed by TaqMan real-time PCR assay, and the association with dengue severity was examined. RESULTS: The rs9277534 variant of HLA-DPB1 was weakly associated with DHF. The genotype GG and G allele conferred protection against DHF (p = 0.04, odds ratio 0.74 for GG genotype, p = 0.03, odds ratio 0.79 for G allele). The association became borderline significant after adjusting for confounders (p = 0.05, odds ratio 0.82). No association was detected for IFNL3 or CD27. CONCLUSIONS: The present study demonstrated the weak association of the rs9277534 variant of HLA-DPB1 with protection against DHF. This variant is in the 3' untranslated region and affects HLA-DPB1 surface protein expression. Our finding suggests that HLA-DPB1 may be involved in DHF pathogenesis.


Asunto(s)
Virus del Dengue/genética , Virus del Dengue/inmunología , Cadenas beta de HLA-DP/genética , Interferones/genética , Dengue Grave/epidemiología , Dengue Grave/genética , Índice de Severidad de la Enfermedad , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/genética , Regiones no Traducidas 3'/genética , Adolescente , Alelos , Estudios de Casos y Controles , Niño , Virus del Dengue/aislamiento & purificación , Femenino , Estudios de Asociación Genética , Genotipo , Humanos , Masculino , Oportunidad Relativa , Polimorfismo de Nucleótido Simple , Dengue Grave/virología , Tailandia/epidemiología
9.
BMJ Case Rep ; 13(12)2020 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-33370956

RESUMEN

COVID-19, caused by SARS-CoV-2, has spread globally. Coinfection with other endemic viruses is likely to complicate the clinical presentation and outcome. Information on clinical manifestations and management strategies on COVID-19 coinfection with endemic diseases in children is yet to evolve. The risk of dengue infection exists in 129 countries and it is endemic in more than 100 countries. The SARS-CoV-2 pandemic might overlap with the dengue epidemics in tropical countries. We report the first paediatric case to the best of our knowledge of COVID-19 encephalitis with dengue shock syndrome. This clinical syndrome could be attributed to serological cross-reactivity, incidental coinfection or perhaps a warning for dengue-endemic regions to face the unique challenge of differentiating and managing two disease entities together. Enhanced understanding of potential COVID-19 and dengue coinfection warrants immediate attention of researchers and international health policy makers.


Asunto(s)
/epidemiología , Coinfección/epidemiología , Virus del Dengue/inmunología , Pandemias , Dengue Grave/epidemiología , Adolescente , Anticuerpos Antivirales/análisis , Femenino , Humanos , Dengue Grave/diagnóstico , Tomografía Computarizada por Rayos X
10.
BMC Infect Dis ; 20(1): 835, 2020 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-33176708

RESUMEN

BACKGROUND: The spatial distribution and burden of dengue in sub-Saharan Africa remains highly uncertain, despite high levels of ecological suitability. The goal of this study was to describe the epidemiology of dengue among a cohort of febrile children presenting to outpatient facilities located in areas of western Uganda with differing levels of urbanicity and malaria transmission intensity. METHODS: Eligible children were first screened for malaria using rapid diagnostic tests. Children with a negative malaria result were tested for dengue using a combination NS1/IgM/IgG rapid test (SD Bioline Dengue Duo). Confirmatory testing by RT-PCR was performed in a subset of participants. Antigen-capture ELISA was performed to estimate seroprevalence. RESULTS: Only 6 of 1416 (0.42%) children had a positive dengue rapid test, while none of the RT-PCR results were positive. ELISA testing demonstrated reactive IgG antibodies in 28 (2.2%) participants with the highest prevalence seen at the urban site in Mbarara (19 of 392, 4.9%, p < 0.001). CONCLUSIONS: Overall, these findings suggest that dengue, while present, is an uncommon cause of non-malarial, pediatric febrile illness in western Uganda. Further investigation into the eocological factors that sustain low-level transmission in urban settings are urgently needed to reduce the risk of epidemics.


Asunto(s)
Virus del Dengue/genética , Virus del Dengue/inmunología , Dengue/diagnóstico , Dengue/epidemiología , Fiebre/diagnóstico , Adolescente , Niño , Preescolar , Dengue/virología , Pruebas Diagnósticas de Rutina/efectos adversos , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Malaria/diagnóstico , Malaria/epidemiología , Malaria/parasitología , Masculino , Plasmodium/inmunología , Plasmodium/aislamiento & purificación , Prevalencia , Estudios Prospectivos , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Seroepidemiológicos , Uganda/epidemiología
11.
Sheng Wu Gong Cheng Xue Bao ; 36(10): 2206-2215, 2020 Oct 25.
Artículo en Chino | MEDLINE | ID: mdl-33169584

RESUMEN

Dengue virus (DENV) is the most widely transmitted arbovirus in the world. Due to the lack of diagnostic technology to quickly identify the virus serotypes in patients, severe dengue hemorrhagic fever cases caused by repeated infections remain high. To realize the rapid differential diagnosis of different serotypes of DENV infection by immunological methods, in this study, four DENV serotype NS1 proteins were expressed and purified in mammalian cells. Monoclonal antibodies (MAbs) against NS1 protein were obtained by hybridoma technology after immunizing BALB/c mice. Enzyme-linked immunosorbent assay, indirect immunofluorescence assay, dot blotting, and Western blotting were used to confirm the reactivity of MAbs to viral native NS1 and recombinant NS1 protein. These MAbs include not only the universal antibodies that recognize all DENV 1-4 serotype NS1, but also serotype-specific antibodies against DENV-1, DENV-2 and DENV-4. Double antibody sandwich ELISA was established based on these antibodies, which can be used to achieve rapid differential diagnosis of serotypes of DENV infection. Preparation of DENV serotype-specific MAbs and establishment of an ELISA technology for identifying DENV serotypes has laid the foundation for the rapid diagnosis of DENV clinical infection.


Asunto(s)
Anticuerpos Antivirales , Virus del Dengue , Dengue , Animales , Anticuerpos Monoclonales , Anticuerpos Antivirales/clasificación , Anticuerpos Antivirales/genética , Anticuerpos Antivirales/metabolismo , Dengue/diagnóstico , Virus del Dengue/inmunología , Ensayo de Inmunoadsorción Enzimática , Humanos , Ratones , Ratones Endogámicos BALB C , Sensibilidad y Especificidad , Serogrupo , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/inmunología
12.
PLoS One ; 15(10): e0238609, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33112881

RESUMEN

INTRODUCTION: Although immune responses to the Japanese Encephalitis virus (JEV), and the dengue viruses (DENV) have a potential to modulate the immune responses to each other, this has been poorly investigated. Therefore, we developed an ELISA to identify JEV specific, DENV non cross-reactive antibody responses by identifying JEV specific, highly conserved regions of the virus and proceeded to investigate if the presence of JEV specific antibodies associate with dengue disease severity. METHODOLOGY AND RESULTS: 22 JEV specific peptides were identified from highly conserved regions of the virus and the immunogenicity and specificity of these peptides were assessed in individuals who were non-immune to JEV and DENV (JEV-DENV-, N = 30), those who were only immune to the JEV and not DENV (JEV+DENV-, N = 30), those who were only immune to DENV(JEV-DENV+, N = 30) and in those who were immune to both viruses (JEV+DENV+, N = 30). 7/22 peptides were found to be highly immunogenic and specific and these 7 peptides were used as a pool to further evaluate JEV-specific responses. All 30/30 JEV+DENV- and 30/30 JEV+DENV+ individuals, and only 3/30 (10%) JEV-DENV+ individuals responded to this pool. We further evaluated this pool of 7 peptides in patients following primary and secondary dengue infection during the convalescent period and found that the JEV-specific peptides, were unlikely to cross react with DENV IgG antibodies. We further compared this in-house ELISA developed with the peptide pool with an existing commercial JEV IgG assay to identify JEV-specific IgG following vaccination, and our in-house ELISA was found to be more sensitive. We then proceeded to investigate if the presence of JEV-specific antibodies were associated with dengue disease severity, and we found that those who had past severe dengue (n = 175) were significantly more likely (p<0.0001) to have JEV-specific antibodies than those with past non-severe dengue (n = 175) (OR 5.3, 95% CI 3.3 to 8.3). CONCLUSIONS: As our data show that this assay is highly sensitive and specific for detection of JEV-specific antibody responses, it would be an important tool to determine how JEV seropositivity modulate dengue immunity and disease severity when undertaking dengue vaccine trials.


Asunto(s)
Anticuerpos Antivirales/sangre , Virus de la Encefalitis Japonesa (Especie)/inmunología , Ensayo de Inmunoadsorción Enzimática/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Aminoácidos , Especificidad de Anticuerpos , Niño , Secuencia Conservada , Reacciones Cruzadas , Dengue/inmunología , Dengue/virología , Virus del Dengue/clasificación , Virus del Dengue/genética , Virus del Dengue/inmunología , Virus de la Encefalitis Japonesa (Especie)/genética , Encefalitis Japonesa/epidemiología , Encefalitis Japonesa/inmunología , Encefalitis Japonesa/virología , Ensayo de Inmunoadsorción Enzimática/estadística & datos numéricos , Femenino , Voluntarios Sanos , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/inmunología , Sensibilidad y Especificidad , Estudios Seroepidemiológicos , Serogrupo , Sri Lanka/epidemiología , Vacunación , Proteínas Virales/genética , Proteínas Virales/inmunología , Adulto Joven
13.
BMC Infect Dis ; 20(1): 639, 2020 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-32867694

RESUMEN

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.


Asunto(s)
Anticuerpos Antivirales/sangre , Virus del Dengue/inmunología , Dengue/sangre , Dengue/epidemiología , Fiebre/sangre , Fiebre/epidemiología , Adolescente , Adulto , Animales , Estudios Transversales , Dengue/diagnóstico , Dengue/virología , Etiopía/epidemiología , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Encuestas y Cuestionarios , Adulto Joven
14.
PLoS Negl Trop Dis ; 14(9): e0008676, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32956362

RESUMEN

Dengue virus (DENV)-associated disease is a growing threat to public health across the globe. Co-circulating as four different serotypes, DENV poses a unique challenge for vaccine design as immunity to one serotype predisposes a person to severe and potentially lethal disease upon infection from other serotypes. Recent experimental studies suggest that an effective vaccine against DENV should elicit a strong T cell response against all serotypes, which could be achieved by directing T cell responses toward cross-serotypically conserved epitopes while avoiding serotype-specific ones. Here, we used experimentally-determined DENV T cell epitopes and patient-derived DENV sequences to assess the cross-serotypic variability of the epitopes. We reveal a distinct near-binary pattern of epitope conservation across serotypes for a large number of DENV epitopes. Based on the conservation profile, we identify a set of 55 epitopes that are highly conserved in at least 3 serotypes. Most of the highly conserved epitopes lie in functionally important regions of DENV non-structural proteins. By considering the global distribution of human leukocyte antigen (HLA) alleles associated with these DENV epitopes, we identify a potentially robust subset of HLA class I and class II restricted epitopes that can serve as targets for a universal T cell-based vaccine against DENV while covering ~99% of the global population.


Asunto(s)
Reacciones Cruzadas/inmunología , Vacunas contra el Dengue/inmunología , Epítopos de Linfocito T/inmunología , Linfocitos T/inmunología , Dengue/prevención & control , Vacunas contra el Dengue/genética , Virus del Dengue/inmunología , Antígenos HLA/genética , Antígenos HLA/inmunología , Humanos , Modelos Moleculares , Estructura Terciaria de Proteína , Proteoma , Análisis de Secuencia de Proteína , Serogrupo
15.
Int J Infect Dis ; 100: 483-489, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32920233

RESUMEN

Antibody-dependent enhancement (ADE) exists in several kinds of virus. It has a negative influence on antibody therapy for viral infection. This effect was first identified in dengue virus and has since also been described for coronavirus. To date, the rapid spread of the newly emerged coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has affected over 3.8 million people across the globe. The novel coronavirus poses a great challenge and has caused a wave of panic. In this review, antibody-dependent enhancements in dengue virus and two kinds of coronavirus are summarized. Possible solutions for the effects are reported. We also speculate that ADE may exist in SARS-CoV-2.


Asunto(s)
Acrecentamiento Dependiente de Anticuerpo , Betacoronavirus/inmunología , Infecciones por Coronavirus/inmunología , Neumonía Viral/inmunología , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/virología , Virus del Dengue/inmunología , Virus del Dengue/patogenicidad , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/inmunología , Coronavirus del Síndrome Respiratorio de Oriente Medio/patogenicidad , Pandemias , Neumonía Viral/virología , Vacunas Virales/inmunología
16.
Am J Trop Med Hyg ; 103(5): 2054-2058, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32876014

RESUMEN

The incidence and spread of dengue virus (DENV) have increased rapidly in recent decades. Dengue is underreported in Africa, but recent outbreaks and seroprevalence data suggest that DENV is widespread there. A lack of ongoing surveillance limits knowledge about its spatial reach and hinders disease control planning. We sought to add data on dengue distribution in Kenya through diagnostic testing of serum specimens from persons with an acute febrile illness (AFI) attending an outpatient clinic in rural western Kenya (Asembo) during rainy seasons. Patients with symptoms not likely to be misclassified as dengue (e.g., diarrhea and anemia), those with a positive diagnostic laboratory results which explained their febrile illness, or those with serum collected more than 5 days after fever onset were excluded. However, febrile patients with a positive malaria smear were included in the study. We used reverse transcription polymerase chain reaction (RT-PCR) to test for DENV and IgM anti-DENV to test for recent infection. Of the 615 serum specimens available for testing, none were dengue positive by either RT-PCR or IgM anti-DENV testing. Dengue did not appear to be a cause of febrile illness in this area of western Kenya, although our relatively small sample size may not have identified DENV infections occurring at low incidence. A more widespread AFI surveillance system that includes dengue diagnostic testing by RT-PCR and antibody-based methods is required to more definitively gauge the size and geographic distribution of DENV infection in western Kenya.


Asunto(s)
Virus del Dengue/inmunología , Dengue/epidemiología , Enfermedad Aguda/epidemiología , Adolescente , Adulto , Niño , Preescolar , Dengue/virología , Virus del Dengue/genética , Monitoreo Epidemiológico , Femenino , Fiebre , Humanos , Lactante , Kenia/epidemiología , Masculino , Adulto Joven
17.
PLoS Negl Trop Dis ; 14(8): e0008660, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32866199

RESUMEN

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.


Asunto(s)
Aedes/virología , Péptidos Catiónicos Antimicrobianos/farmacología , Virus del Dengue/inmunología , Quinasas de Proteína Quinasa Activadas por Mitógenos/farmacología , Mosquitos Vectores/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Animales , Antiinfecciosos/farmacología , Línea Celular , Sistema Digestivo/virología , Femenino , Perfilación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Inmunidad Innata , Quinasas de Proteína Quinasa Activadas por Mitógenos/genética , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Mosquitos Vectores/virología , Carga Viral , Replicación Viral/efectos de los fármacos
18.
PLoS Pathog ; 16(8): e1008754, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32776975

RESUMEN

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.


Asunto(s)
Aedes/inmunología , Apoptosis , Fiebre Chikungunya/inmunología , Proteínas del Sistema Complemento/inmunología , Dengue/inmunología , Sistema de Señalización de MAP Quinasas , Glándulas Salivales/inmunología , Infección por el Virus Zika/inmunología , Aedes/virología , Animales , Fiebre Chikungunya/metabolismo , Fiebre Chikungunya/prevención & control , Fiebre Chikungunya/virología , Virus Chikungunya/inmunología , Proteínas del Sistema Complemento/metabolismo , Dengue/metabolismo , Dengue/prevención & control , Dengue/virología , Virus del Dengue/inmunología , Femenino , Interacciones Huésped-Patógeno , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Insectos Vectores/inmunología , Insectos Vectores/virología , Glándulas Salivales/virología , Transcriptoma , Replicación Viral , Virus Zika/inmunología , Infección por el Virus Zika/metabolismo , Infección por el Virus Zika/prevención & control , Infección por el Virus Zika/virología
19.
Nat Rev Immunol ; 20(10): 633-643, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32782358

RESUMEN

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.


Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Antivirales/administración & dosificación , Acrecentamiento Dependiente de Anticuerpo/efectos de los fármacos , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Leucocitos/efectos de los fármacos , Neumonía Viral/tratamiento farmacológico , Receptores de IgG/inmunología , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/biosíntesis , Anticuerpos Neutralizantes/administración & dosificación , Anticuerpos Neutralizantes/efectos adversos , Anticuerpos Neutralizantes/biosíntesis , Anticuerpos Antivirales/efectos adversos , Anticuerpos Antivirales/biosíntesis , Betacoronavirus/inmunología , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Dengue/tratamiento farmacológico , Dengue/inmunología , Dengue/virología , Virus del Dengue/efectos de los fármacos , Virus del Dengue/inmunología , Virus del Dengue/patogenicidad , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno/efectos de los fármacos , Interacciones Huésped-Patógeno/inmunología , Humanos , Leucocitos/inmunología , Leucocitos/virología , Pandemias , Neumonía Viral/inmunología , Neumonía Viral/virología , Receptores de IgG/antagonistas & inhibidores , Receptores de IgG/genética , Virus del SRAS/efectos de los fármacos , Virus del SRAS/inmunología , Virus del SRAS/patogenicidad , Síndrome Respiratorio Agudo Grave/tratamiento farmacológico , Síndrome Respiratorio Agudo Grave/inmunología , Síndrome Respiratorio Agudo Grave/virología , Transducción de Señal , Internalización del Virus/efectos de los fármacos
20.
PLoS Negl Trop Dis ; 14(8): e0008535, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32813703

RESUMEN

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.


Asunto(s)
Dengue/diagnóstico , Dengue/epidemiología , Adolescente , Adulto , Anticuerpos Antivirales/inmunología , Niño , Preescolar , Dengue/inmunología , Virus del Dengue/inmunología , Brotes de Enfermedades , Ensayo de Inmunoadsorción Enzimática , Femenino , Guatemala/epidemiología , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Serogrupo , Serotipificación/métodos , Adulto Joven
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