Topic
Dengue virus
About: Dengue virus is a research topic. Over the lifetime, 12671 publications have been published within this topic receiving 461406 citations. The topic is also known as: DENV.
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TL;DR: A fluorogenic reverse transcriptase-polymerase chain reaction (RT-PCR) system was developed for use as a rapid diagnostic test for determining dengue viremia and demonstrated high level detection sensitivity and specificity for all four d Dengue virus serotypes.
158 citations
TL;DR: Blood transfusions are safer now than ever before and the authors have learnt how to mitigate risks of emerging infectious diseases such as West Nile, Chikungunya, and Dengue viruses.
158 citations
TL;DR: The structure reveals the mechanism by which this potent and specific antibody blocks viral infection and shows that HMAb 1F4 can neutralize DENV at different stages of viral entry in a cell type and receptor dependent manner.
Abstract: Dengue virus (DENV), which consists of four serotypes (DENV1-4), infects over 400 million people annually. Previous studies have indicated most human monoclonal antibodies (HMAbs) from dengue patients are cross-reactive and poorly neutralizing. Rare neutralizing HMAbs are usually serotype-specific and bind to quaternary structure-dependent epitopes. We determined the structure of DENV1 complexed with Fab fragments of a highly potent HMAb 1F4 to 6 A resolution by cryo-EM. Although HMAb 1F4 appeared to bind to virus and not E proteins in ELISAs in the previous study, our structure showed that the epitope is located within an envelope (E) protein monomer, and not across neighboring E proteins. The Fab molecules bind to domain I (DI), and DI-DII hinge of the E protein. We also showed that HMAb 1F4 can neutralize DENV at different stages of viral entry in a cell type and receptor dependent manner. The structure reveals the mechanism by which this potent and specific antibody blocks viral infection.
158 citations
TL;DR: The mechanisms initiating and sustaining adaptive immune responses during primary infection with the immune pathways that are pre-existing and reactivated during secondary dengue are contrasted.
Abstract: Dengue is the leading mosquito-borne viral illness infecting humans. Owing to the circulation of multiple serotypes, global expansion of the disease and recent gains in vaccination coverage, pre-existing immunity to dengue virus is abundant in the human population, and secondary dengue infections are common. Here, we contrast the mechanisms initiating and sustaining adaptive immune responses during primary infection with the immune pathways that are pre-existing and reactivated during secondary dengue. We also discuss new developments in our understanding of the contributions of CD4+ T cells, CD8+ T cells and antibodies to immunity and memory recall. Memory recall may lead to protective or pathological outcomes, and understanding of these processes will be key to developing or refining dengue vaccines to be safe and effective. The existence of four different serotypes of dengue virus poses a challenge to vaccine development, as pre-existing immunity can lead to severe disease during infection with a heterologous serotype. This Review analyses the mechanisms of protective and pathological adaptive immune responses in primary and secondary dengue infection.
157 citations
Icahn School of Medicine at Mount Sinai1, Massachusetts Institute of Technology2, South Colombian University3, Harvard University4, Industrial University of Santander5, Universidade Federal de Minas Gerais6, Universidade Federal de Sergipe7, Mexican Social Security Institute8, Instituto Politécnico Nacional9, Faculdade de Medicina de São José do Rio Preto10, Oswaldo Cruz Foundation11, University of Pittsburgh12, Colorado State University13, University of Antioquia14, University of Córdoba (Spain)15, University of Colorado Denver16, All India Institute of Medical Sciences17, Translational Health Science and Technology Institute18, Central University of Venezuela19, University of Massachusetts Boston20
TL;DR: The characterization of monoclonal antibody pairs that have been translated into rapid immunochromatography tests to specifically detect the viral nonstructural 1 (NS1) protein antigen and distinguish the four DENV serotypes (DENV1–4) and ZIKV without cross-reaction are reported.
Abstract: The recent Zika virus (ZIKV) outbreak demonstrates that cost-effective clinical diagnostics are urgently needed to detect and distinguish viral infections to improve patient care. Unlike dengue virus (DENV), ZIKV infections during pregnancy correlate with severe birth defects, including microcephaly and neurological disorders. Because ZIKV and DENV are related flaviviruses, their homologous proteins and nucleic acids can cause cross-reactions and false-positive results in molecular, antigenic, and serologic diagnostics. We report the characterization of monoclonal antibody pairs that have been translated into rapid immunochromatography tests to specifically detect the viral nonstructural 1 (NS1) protein antigen and distinguish the four DENV serotypes (DENV1-4) and ZIKV without cross-reaction. To complement visual test analysis and remove user subjectivity in reading test results, we used image processing and data analysis for data capture and test result quantification. Using a 30-μl serum sample, the sensitivity and specificity values of the DENV1-4 tests and the pan-DENV test, which detects all four dengue serotypes, ranged from 0.76 to 1.00. Sensitivity/specificity for the ZIKV rapid test was 0.81/0.86, respectively, using a 150-μl serum input. Serum ZIKV NS1 protein concentrations were about 10-fold lower than corresponding DENV NS1 concentrations in infected patients; moreover, ZIKV NS1 protein was not detected in polymerase chain reaction-positive patient urine samples. Our rapid immunochromatography approach and reagents have immediate application in differential clinical diagnosis of acute ZIKV and DENV cases, and the platform can be applied toward developing rapid antigen diagnostics for emerging viruses.
157 citations