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Sample records for dengue virus infections

  1. Cells in Dengue Virus Infection In Vivo

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    Sansanee Noisakran

    2010-01-01

    Full Text Available Dengue has been recognized as one of the most important vector-borne emerging infectious diseases globally. Though dengue normally causes a self-limiting infection, some patients may develop a life-threatening illness, dengue hemorrhagic fever (DHF/dengue shock syndrome (DSS. The reason why DHF/DSS occurs in certain individuals is unclear. Studies in the endemic regions suggest that the preexisting antibodies are a risk factor for DHF/DSS. Viremia and thrombocytopenia are the key clinical features of dengue virus infection in patients. The amounts of virus circulating in patients are highly correlated with severe dengue disease, DHF/DSS. Also, the disturbance, mainly a transient depression, of hematological cells is a critical clinical finding in acute dengue patients. However, the cells responsible for the dengue viremia are unresolved in spite of the intensive efforts been made. Dengue virus appears to replicate and proliferate in many adapted cell lines, but these in vitro properties are extremely difficult to be reproduced in primary cells or in vivo. This paper summarizes reports on the permissive cells in vitro and in vivo and suggests a hematological cell lineage for dengue virus infection in vivo, with the hope that a new focus will shed light on further understanding of the complexities of dengue disease.

  2. Pharmacological intervention for dengue virus infection.

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    Lai, Jenn-Haung; Lin, Yi-Ling; Hsieh, Shie-Liang

    2017-04-01

    Dengue virus (DENV) infection has a considerable health impact in tropical and subtropical countries worldwide. Escalation of infection rates greatly increases morbidity and mortality, most commonly from deaths due to dengue hemorrhagic fever and dengue shock syndrome. Although the development of an effective, long-lasting vaccine has been a major aim for control and prevention of DENV infection, the currently licensed vaccine has limitations and is less than satisfactory. Thus, there remains an important need to identify effective and tolerable medications for treatment of DENV-infected patients both in the early phase, to prevent progression to fatal outcomes, and to minimize deaths after patients develop severe complications. This review will address several specific points, including (1) approaches to identify anti-DENV medications, (2) recent advances in the development of potential compounds targeting DENV infection, (3) experience with clinical trials of regimens for DENV infection, (4) some available medications of potential for clinical trials against DENV infection, (5) reasons for unsuccessful outcomes and challenges of anti-DENV treatments, and (6) directions for developing or selecting better anti-DENV strategies. This review provides useful guidance for clinicians selecting drugs for DENV-infected patients with severe manifestations or potential fatal disease progression, and for basic researchers seeking to develop effective anti-DENV regimens. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Roles for Endothelial Cells in Dengue Virus Infection

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    Nadine A. Dalrymple

    2012-01-01

    Full Text Available Dengue viruses cause two severe diseases that alter vascular fluid barrier functions, dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS. The endothelium is the primary fluid barrier of the vasculature and ultimately the effects of dengue virus infection that cause capillary leakage impact endothelial cell (EC barrier functions. The ability of dengue virus to infect the endothelium provides a direct means for dengue to alter capillary permeability, permit virus replication, and induce responses that recruit immune cells to the endothelium. Recent studies focused on dengue virus infection of primary ECs have demonstrated that ECs are efficiently infected, rapidly produce viral progeny, and elicit immune enhancing cytokine responses that may contribute to pathogenesis. Furthermore, infected ECs have also been implicated in enhancing viremia and immunopathogenesis within murine dengue disease models. Thus dengue-infected ECs have the potential to directly contribute to immune enhancement, capillary permeability, viremia, and immune targeting of the endothelium. These effects implicate responses of the infected endothelium in dengue pathogenesis and rationalize therapeutic targeting of the endothelium and EC responses as a means of reducing the severity of dengue virus disease.

  4. Immune Activation in the Pathogenesis of Dengue Virus Infection

    NARCIS (Netherlands)

    C.A.M. van de Weg (Cornelia A.M.)

    2014-01-01

    markdownabstract__Abstract__ Dengue virus (DENV) is a positive-stranded RNA virus and belongs to the Flaviviridae family. The virus is transmitted by the bite of an infected Aedes-mosquito and circulates in tropical and subtropical areas around the world. The incidence of dengue has risen

  5. Host cell responses to dengue virus infection

    NARCIS (Netherlands)

    Diosa Toro, Mayra

    2017-01-01

    Dengue (ook wel knokkelkoorts) is de meest voorkomende virale infectieziekte dat wordt overgedragen door muggen in de wereld met naar schatting 390 miljoen infecties per jaar. Ondanks de grote klinische impact en economische schade van het dengue virus is er nog steeds geen behandeling beschikbaar.

  6. Towards antiviral therapies for treating dengue virus infections.

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    Kaptein, Suzanne Jf; Neyts, Johan

    2016-10-01

    Dengue virus is an emerging human pathogen that poses a huge public health burden by infecting annually about 390 million individuals of which a quarter report with clinical manifestations. Although progress has been made in understanding dengue pathogenesis, a licensed vaccine or antiviral therapy against this virus is still lacking. Treatment of patients is confined to symptomatic alleviation and supportive care. The development of dengue therapeutics thus remains of utmost importance. This review focuses on the few molecules that were evaluated in dengue virus-infected patients: balapiravir, chloroquine, lovastatin, prednisolone and celgosivir. The lessons learned from these clinical trials can be very helpful for the design of future trials for the next generation of dengue virus inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Seroepidemiology of Asymptomatic Dengue Virus Infection in Jeddah, Saudi Arabia

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    Ghazi A. Jamjoom

    2016-01-01

    Full Text Available Background Although virologically confirmed dengue fever has been recognized in Jeddah, Saudi Arabia, since 1994, causing yearly outbreaks, no proper seroepidemiologic studies on dengue virus have been conducted in this region. Such studies can define the extent of infection by this virus and estimate the proportion that may result in disease. The aim of this study was to measure the seroprevalence of past dengue virus infection in healthy Saudi nationals from different areas in the city of Jeddah and to investigate demographic and environmental factors that may increase exposure to infection. Methods Sera were collected from 1984 Saudi subjects attending primary health care centers in six districts of Jeddah. These included general patients of various ages seeking routine vaccinations, antenatal care or treatment of different illnesses excluding fever or suspected dengue. A number of blood donors were also tested. Serum samples were tested by enzyme immunoassay (EIA for IgG antibodies to dengue viruses 1, 2, 3, 4. A questionnaire was completed for each patient recording various anthropometric data and factors that may indicate possible risk of exposure to mosquito bites and dengue infection. Patients with missing data and those who reported a history of dengue fever were excluded from analysis, resulting in a sample of 1939 patients to be analyzed. Results The overall prevalence of dengue virus infection as measured by anti-dengue IgG antibodies from asymptomatic residents in Jeddah was 47.8% (927/1939 and 37% (68/184 in blood donors. Infection mostly did not result in recognizable disease, as only 19 of 1956 subjects with complete information (0.1% reported having dengue fever in the past. Anti dengue seropositivity increased with age and was higher in males than females and in residents of communal housing and multistory buildings than in villas. One of the six districts showed significant increase in exposure rate as compared to the others

  8. Clinical and laboratory profile of different dengue sub types in dengue virus infection

    OpenAIRE

    Niloy Gan Chaudhuri; S. Vithyavathi; K. Sankar

    2016-01-01

    Background: Dengue infection, an arthropod-borne viral hemorrhagic fever is caused by Arbovirus of Flavivirus genus and transmitted by Aedes aegypti, Aedes albopictus. Liver involvement in dengue fever is manifested by the elevation of transaminases representing reactive hepatitis, due to direct attack of virus itself or the use of hepatotoxic drugs. The objective of the study was to investigate clinical and laboratory profile of different dengue sub type's patients admitted for dengue fever....

  9. NNDSS - Table II. Cryptosporidiosis to Dengue virus infection

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    U.S. Department of Health & Human Services — NNDSS - Table II. Cryptosporidiosis to Dengue virus infection - 2018. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during...

  10. Co-infections with Chikungunya and Dengue Viruses, Guatemala, 2015.

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    Edwards, Thomas; Signor, Leticia Del Carmen Castillo; Williams, Christopher; Donis, Evelin; Cuevas, Luis E; Adams, Emily R

    2016-11-01

    We screened serum samples referred to the national reference laboratory in Guatemala that were positive for chikungunya or dengue viruses in June 2015. Co-infection with both viruses was detected by reverse transcription PCR in 46 (32%) of 144 samples. Specimens should be tested for both arboviruses to detect co-infections.

  11. Dengue NS1 Antigen - for Early Detection of Dengue Virus Infection

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    Amol Hartalkar

    2015-08-01

    Full Text Available Objectives: To evaluate the efficacy of NS1 antigen assay for early diagnosis of dengue virus infection in a tertiary care hospital. Methods: This cross sectional study was carried out in department of Medicine from August to December 2013. Total 100 patients with dengue fever were included. Complete blood count, alanine aminotransferase (ALT, aspartate aminotransferase (AST, Dengue NS1 antigen and IgM and IgG antibodies of dengue virus were done in all cases. Results: Of the 100 sera tested, 75% were positive for dengue virus infection based on dengue NS1 antigen, IgM antibody and IgG antibody. Dengue NS1 antigen and IgM, IgG antibody were able to detect dengue virus infection between day 1 to day 8 in 92% of samples, 86.7% of samples and 82.6% of samples respectively. Sixty nine percent (69% were found positive for dengue NS1 antigen, 65% were IgM positive and 62% were IgG positive. Based on the dengue NS1 antigen and IgM antibody combination, 74% were positive for dengue virus infections. Sensitivity of Dengue NS1 antigen was 92.3% and specificity of 74.28% in comparison to IgM antibody. Detection rate increased to 75%, based on the antigen and IgG antibody combination. Sensitivity of dengue NS1 antigen was 90.3% and specificity of 65.8% in comparison to IgG antibody. Conclusion: Dengue NS1 antigen is a useful, sensitive and specific test for early diagnosis of dengue virus infection and it improves diagnostic efficiency in combination with antibody test. Key words: Dengue fever, NS1 antigen. Introduction: Dengue fever (DF is the most common arboviral illness in humans. Each year, an estimated 50-100 million cases of dengue fever and 500,000 cases of dengue hemorrhagic fever occur worldwide, with 30000 deaths (mainly in children. Globally 2.5-3 billion people in approximately 112 tropical and subtropical countries are at risk of dengue.of samples respectively. Sixty nine percent (69% were found positive for dengue NS1 antigen, 65% were Ig

  12. Virus isolation for diagnosing dengue virus infections in returning travelers

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    Teichmann, D.; Göbels, K.; Niedrig, M.; Sim-Brandenburg, J.-W.; Làge-Stehr, J.; Grobusch, M. P.

    2003-01-01

    Dengue fever is recognized as one of the most frequent imported acute febrile illnesses affecting European tourists returning from the tropics. In order to assess the value of virus isolation for the diagnosis of dengue fever, 70 cases of dengue fever confirmed in German travelers during the period

  13. The Aedes aegypti toll pathway controls dengue virus infection.

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    Zhiyong Xi

    2008-07-01

    Full Text Available Aedes aegypti, the mosquito vector of dengue viruses, utilizes its innate immune system to ward off a variety of pathogens, some of which can cause disease in humans. To date, the features of insects' innate immune defenses against viruses have mainly been studied in the fruit fly Drosophila melanogaster, which appears to utilize different immune pathways against different types of viruses, in addition to an RNA interference-based defense system. We have used the recently released whole-genome sequence of the Ae. aegypti mosquito, in combination with high-throughput gene expression and RNA interference (RNAi-based reverse genetic analyses, to characterize its response to dengue virus infection in different body compartments. We have further addressed the impact of the mosquito's endogenous microbial flora on virus infection. Our findings indicate a significant role for the Toll pathway in regulating resistance to dengue virus, as indicated by an infection-responsive regulation and functional assessment of several Toll pathway-associated genes. We have also shown that the mosquito's natural microbiota play a role in modulating the dengue virus infection, possibly through basal-level stimulation of the Toll immune pathway.

  14. Dengue virus life cycle : viral and host factors modulating infectivity

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    Rodenhuis-Zybert, Izabela A.; Wilschut, Jan; Smit, Jolanda M.

    Dengue virus (DENV 1-4) represents a major emerging arthropod-borne pathogen. All four DENV serotypes are prevalent in the (sub) tropical regions of the world and infect 50-100 million individuals annually. Whereas the majority of DENV infections proceed asymptomatically or result in self-limited

  15. Prevention and Control Strategies to Counter Dengue Virus Infection.

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    Rather, Irfan A; Parray, Hilal A; Lone, Jameel B; Paek, Woon K; Lim, Jeongheui; Bajpai, Vivek K; Park, Yong-Ha

    2017-01-01

    Dengue is currently the highest and rapidly spreading vector-borne viral disease, which can lead to mortality in its severe form. The globally endemic dengue poses as a public health and economic challenge that has been attempted to suppress though application of various prevention and control techniques. Therefore, broad spectrum techniques, that are efficient, cost-effective, and environmentally sustainable, are proposed and practiced in dengue-endemic regions. The development of vaccines and immunotherapies have introduced a new dimension for effective dengue control and prevention. Thus, the present study focuses on the preventive and control strategies that are currently employed to counter dengue. While traditional control strategies bring temporary sustainability alone, implementation of novel biotechnological interventions, such as sterile insect technique, paratransgenesis, and production of genetically modified vectors, has improved the efficacy of the traditional strategies. Although a large-scale vector control strategy can be limited, innovative vaccine candidates have provided evidence for promising dengue prevention measures. The use of tetravalent dengue vaccine (CYD-TDV) has been the most effective so far in treating dengue infections. Nonetheless, challenges and limitation hinder the progress of developing integrated intervention methods and vaccines; while the improvement in the latest techniques and vaccine formulation continues, one can hope for a future without the threat of dengue virus.

  16. Prevention and Control Strategies to Counter Dengue Virus Infection

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    Irfan A. Rather

    2017-07-01

    Full Text Available Dengue is currently the highest and rapidly spreading vector-borne viral disease, which can lead to mortality in its severe form. The globally endemic dengue poses as a public health and economic challenge that has been attempted to suppress though application of various prevention and control techniques. Therefore, broad spectrum techniques, that are efficient, cost-effective, and environmentally sustainable, are proposed and practiced in dengue-endemic regions. The development of vaccines and immunotherapies have introduced a new dimension for effective dengue control and prevention. Thus, the present study focuses on the preventive and control strategies that are currently employed to counter dengue. While traditional control strategies bring temporary sustainability alone, implementation of novel biotechnological interventions, such as sterile insect technique, paratransgenesis, and production of genetically modified vectors, has improved the efficacy of the traditional strategies. Although a large-scale vector control strategy can be limited, innovative vaccine candidates have provided evidence for promising dengue prevention measures. The use of tetravalent dengue vaccine (CYD-TDV has been the most effective so far in treating dengue infections. Nonetheless, challenges and limitation hinder the progress of developing integrated intervention methods and vaccines; while the improvement in the latest techniques and vaccine formulation continues, one can hope for a future without the threat of dengue virus.

  17. Dengue death with evidence of hemophagocytic syndrome and dengue virus infection in the bone marrow.

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    Ab-Rahman, Hasliana Azrah; Wong, Pooi-Fong; Rahim, Hafiz; Abd-Jamil, Juraina; Tan, Kim-Kee; Sulaiman, Syuhaida; Lum, Chai-See; Syed-Omar, Syarifah-Faridah; AbuBakar, Sazaly

    2015-01-01

    HPS is a potentially life-threatening histiocytic disorder that has been described in various viral infections including dengue. Its involvement in severe and fatal dengue is probably more common but is presently under recognized. A 38-year-old female was admitted after 5 days of fever. She was deeply jaundiced, leukopenic and thrombocytopenic. Marked elevation of transaminases, hyperbilirubinemia and hypoalbuminemia were observed. She had deranged INR values and prolonged aPTT accompanied with hypofibrinogenemia. She also had splenomegaly. She was positive for dengue IgM. Five days later she became polyuric and CT brain image showed gross generalized cerebral edema. Her conditions deteriorated by day 9, became confused with GCS of 9/15. Her BMAT showed minimal histiocytes. Her serum ferritin level peaked at 13,670.00 µg/mL and her sCD163 and sCD25 values were markedly elevated at 4750.00 ng/mL and 4191.00 pg/mL, respectively. She succumbed to the disease on day 10 and examination of her tissues showed the presence of dengue virus genome in the bone marrow. It is described here, a case of fatal dengue with clinical features of HPS. Though BMAT results did not show the presence of macrophage hemophagocytosis, other laboratory features were consistent with HPS especially marked elevation of ferritin, sCD163 and sCD25. Detection of dengue virus in the patient's bone marrow, fifteen days after the onset of fever was also consistent with the suggestion that the HPS is associated with dengue virus infection. The findings highlight HPS as a possible complication leading to severe dengue and revealed persistent dengue virus infection of the bone marrow. Detection of HPS markers; ferritin, sCD163 and sCD25, therefore, should be considered for early recognition of HPS-associated dengue.

  18. Gamma interferon augments Fc gamma receptor-mediated dengue virus infection of human monocytic cells.

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    Kontny, U; Kurane, I; Ennis, F A

    1988-01-01

    It has been reported that anti-dengue antibodies at subneutralizing concentrations augment dengue virus infection of monocytic cells. This is due to the increased uptake of dengue virus in the form of virus-antibody complexes by cells via Fc gamma receptors. We analyzed the effects of recombinant human gamma interferon (rIFN-gamma) on dengue virus infection of human monocytic cells. U937 cells, a human monocytic cell line, were infected with dengue virus in the form of virus-antibody complexe...

  19. Role of antibodies in controlling dengue virus infection

    NARCIS (Netherlands)

    van der Schaar, Hilde M.; Wilschut, Jan C.; Smit, Jolanda M.

    The incidence and disease burden of arthropod-borne flavivirus infections have dramatically increased during the last decades due to major societal and economic changes, including massive urbanization, lack of vector control, travel, and international trade. Specifically, in the case of dengue virus

  20. Early diagnosis of dengue virus infection in clinically suspected cases

    International Nuclear Information System (INIS)

    Afridi, N.K.; Ahmed, S.; Ali, N.; Khan, S.A.

    2016-01-01

    Objective: Comparison of real time reverse transcriptase polymerase chain reaction (RTPCR) and immunoglobulin M (IgM) capture enzyme linked immunosorbent assay (ELISA) for diagnosis of dengue virus infection in first week of illness in clinically suspected patients of dengue fever. Study Design: Cross sectional study. Place and Duration of Study: Department of haematology, Armed Forces Institute of Pathology (AFIP) Rawalpindi from Jan 2013 to Nov 2013. Material and Methods: A cross sectional study including 68 clinically suspected patients of dengue fever according to the World Health Organization (WHO) criteria. IgM capture ELISA and RT PCR for dengue virus ribonucleic acid (RNA) was performed on samples collected from patients having fever for 1 to 7 days. These were divided into two groups. Patients in group 1 presented with fever of 4 days or less, patients in group 2 had fever of 5 to 7 days duration. Results: In group 1, 72 percent of the patients were positive by RT PCR while 31 percent were positive by IgM capture ELISA. In group 2, 43 percent of the patients were positive by RT PCR while 97 percent were positive by ELISA. Conclusion: RT PCR can be used for early detection of dengue virus infection in the first few days of fever while IgM ELISA is diagnostic afterwards. (author)

  1. Nine year trends of dengue virus infection in Mumbai, Western India

    OpenAIRE

    Shastri, Jayanthi; Williamson, Manita; Vaidya, Nilima; Agrawal, Sachee; Shrivastav, Om

    2017-01-01

    Introduction: Dengue virus (DENV) causes a wide range of diseases in humans, from acute febrile illness Dengue fever (DF) to life-threatening Dengue hemorrhagic fever (DHF) or Dengue shock syndrome (DSS). Factors believed to be responsible for spread of Dengue virus infection include explosive population growth, unplanned urban overpopulation with inadequate public health systems, poor standing water and vector control, climate changes and increased international recreational, business, milit...

  2. Competitive inhibitor of cellular alpha-glucosidases protects mice from lethal dengue virus infection

    OpenAIRE

    Chang, Jinhong; Schul, Wouter; Yip, Andy; Xu, Xiaodong; Guo, Ju-Tao; Block, Timothy M.

    2011-01-01

    Dengue virus infection causes diseases in people, ranging from the acute febrile illness Dengue fever, to life-threatening Dengue Hemorrhagic Fever/Dengue Shock Syndrome. We previously reported that a host cellular α-glucosidases I and II inhibitor, imino sugar CM-10-18, potently inhibited dengue virus replication in cultured cells, and significantly reduced viremia in dengue virus infected AG129 mice. In this report we show that CM-10-18 also significantly protects mice from death and/or dis...

  3. Proteasome Inhibition Suppresses Dengue Virus Egress in Antibody Dependent Infection.

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    Milly M Choy

    2015-11-01

    Full Text Available The mosquito-borne dengue virus (DENV is a cause of significant global health burden, with an estimated 390 million infections occurring annually. However, no licensed vaccine or specific antiviral treatment for dengue is available. DENV interacts with host cell factors to complete its life cycle although this virus-host interplay remains to be fully elucidated. Many studies have identified the ubiquitin proteasome pathway (UPP to be important for successful DENV production, but how the UPP contributes to DENV life cycle as host factors remains ill defined. We show here that proteasome inhibition decouples infectious virus production from viral RNA replication in antibody-dependent infection of THP-1 cells. Molecular and imaging analyses in β-lactone treated THP-1 cells suggest that proteasome function does not prevent virus assembly but rather DENV egress. Intriguingly, the licensed proteasome inhibitor, bortezomib, is able to inhibit DENV titers at low nanomolar drug concentrations for different strains of all four serotypes of DENV in primary monocytes. Furthermore, bortezomib treatment of DENV-infected mice inhibited the spread of DENV in the spleen as well as the overall pathological changes. Our findings suggest that preventing DENV egress through proteasome inhibition could be a suitable therapeutic strategy against dengue.

  4. Treatment Effectiveness of Amantadine Against Dengue Virus Infection.

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    Lin, Chieh-Cheng; Chen, Wen-Ching

    2016-12-05

    BACKGROUND About 400 million cases of dengue, a mosquito-borne disease, are reported annually, but no drug is yet available for treatment. In 1988, at Feng Lin Clinic, Taiwan, we encountered about 10,000 cases and tested various drugs before confirming an antiviral effect of amantadine against dengue virus in vitro. After we administered amantadine to patients for 1-2 days, most achieved full remission. None experienced potentially life-threatening dengue hemorrhagic fever or dengue shock syndrome. Herein, we present 34 cases from recent clinical experience that show amantadine's unusual effect against dengue virus infection. CASE REPORT We divided 34 patients with symptoms of dengue fever, confirmed by a screening test, into 3 groups: 6 Category 1 patients received amantadine at onset, 21 Category 2 patients received amantadine within 2-6 days, and 7 Contrast group patients received no amantadine because they visited other clinics or were admitted to a large hospital. When Category 1 patients were treated with amantadine 100 mg 3 times per day, all symptoms dramatically subsided within 1-2 days. In Category 2 patients, most symptoms diminished within 1-2 days after starting the same regimen. In the Contrast group, all symptoms persisted 7 days after onset. White blood cell and platelet counts in Category 1 and 2 patients recovered to normal range, but remained below low normal in the Contrast group. CONCLUSIONS Amantadine is effective and should be given as soon as possible to stop the disease course if dengue fever is confirmed through screening or clinical signs and symptoms. A well-designed larger sample study is warranted to test this effectiveness.

  5. THE CHANGING CLINICAL PERFORMANCE OF DENGUE VIRUS INFECTION IN THE YEAR 2009

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    Soegeng Soegijanto

    2012-01-01

    Full Text Available Background: Dengue (DEN virus, the most important arthropod-borne human pathogen, represents a serious public health threat. DEN virus is transmitted to humans by the bite of the domestic mosquito, Aedes aegypti, and circulates in nature as four distinct serological types DEN-1 to 4. The aim of Study: To identify Dengue Virus Serotype I which showed mild clinical performance in five years before and afterward showed severe clinical performance. Material and Method: Prospective and analytic observational study had been done in Dr. Soetomo Hospital and the ethical clearance was conduct on January 01, 2009. The population of this research is all cases of dengue virus infection. Diagnosis were done based on WHO 1997. All of these cases were examined for IgM & IgG anti Dengue Virus and then were followed by PCR examination to identify Dengue Virus serotype. Result and Discussion: DEN 2 was predominant virus serotype with produced a spectrum clinical illness from asymptomatic, mild illness to classic dengue fever (DF to the most severe form of illness (DHF. But DEN 1 usually showed mild illness. Helen at al (2009–2010 epidemiologic study of Dengue Virus Infection in Health Centre Surabaya and Mother and Child Health Soerya Sidoarjo found many cases of Dengue Hemorrhagic Fever were caused by DEN 1 Genotype IV. Amor (2009 study in Dr. Soetomo Hospital found DEN 1 showed severe clinical performance of primary Dengue Virus Infection as Dengue Shock Syndrome two cases and one unusual case. Conclusion: The epidemiologic study of Dengue Virus Infection in Surabaya and Sidoarjo; in the year 2009 found changing predominant Dengue Virus Serotype from Dengue Virus II to Dengue Virus 1 Genotype IV which showed a severe clinical performance coincident with primary infection.

  6. The cellular bases of antibody responses during dengue virus infection

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    Juan Carlos Yam-Puc

    2016-06-01

    Full Text Available Dengue virus (DENV is one of the most significant human viral pathogens transmitted by mosquitoes and can cause from an asymptomatic disease to mild undifferentiated fever, classical dengue, and severe dengue. Neutralizing memory antibody (Ab responses are one of the most important mechanisms that counteract reinfections and are therefore the main aim of vaccination. However, it has also been proposed that in dengue, some of these class-switched (IgG memory Abs might worsen the disease. Although these memory Abs derive from B cells by T-cell dependent processes, we know rather little about the (acute, chronic or memory B cell responses and the complex cellular mechanisms generating these Abs during DENV infections.This review aims to provide an updated and comprehensive perspective of the B cell responses during DENV infection, starting since the very early events like the cutaneous DENV entrance and the arrival into draining lymph nodes, to the putative B cell activation, proliferation and germinal centers (GCs formation (the source of affinity-matured class-switched memory Abs, till the outcome of GC reactions such as the generation of plasmablasts, Ab-secreting plasma cells and memory B cells. We discuss topics very poorly explored such as the possibility of B cell infection by DENV or even activation-induced B cell death. The current information about the nature of the Ab responses to DENV is also illustrated.

  7. Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection.

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    Michael J Conway

    2016-09-01

    Full Text Available Aedes aegypti is the primary vector of several medically relevant arboviruses including dengue virus (DENV types 1-4. Ae. aegypti transmits DENV by inoculating virus-infected saliva into host skin during probing and feeding. Ae. aegypti saliva contains over one hundred unique proteins and these proteins have diverse functions, including facilitating blood feeding. Previously, we showed that Ae. aegypti salivary gland extracts (SGEs enhanced dissemination of DENV to draining lymph nodes. In contrast, HPLC-fractionation revealed that some SGE components inhibited infection. Here, we show that D7 proteins are enriched in HPLC fractions that are inhibitory to DENV infection, and that recombinant D7 protein can inhibit DENV infection in vitro and in vivo. Further, binding assays indicate that D7 protein can directly interact with DENV virions and recombinant DENV envelope protein. These data reveal a novel role for D7 proteins, which inhibits arbovirus transmission to vertebrates through a direct interaction with virions.

  8. Molecular classification of outcomes from dengue virus -3 infections.

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    Brasier, Allan R; Zhao, Yingxin; Wiktorowicz, John E; Spratt, Heidi M; Nascimento, Eduardo J M; Cordeiro, Marli T; Soman, Kizhake V; Ju, Hyunsu; Recinos, Adrian; Stafford, Susan; Wu, Zheng; Marques, Ernesto T A; Vasilakis, Nikos

    2015-03-01

    Dengue virus (DENV) infection is a significant risk to over a third of the human population that causes a wide spectrum of illness, ranging from sub-clinical disease to intermediate syndrome of vascular complications called dengue fever complicated (DFC) and severe, dengue hemorrhagic fever (DHF). Methods for discriminating outcomes will impact clinical trials and understanding disease pathophysiology. We integrated a proteomics discovery pipeline with a heuristics approach to develop a molecular classifier to identify an intermediate phenotype of DENV-3 infectious outcome. 121 differentially expressed proteins were identified in plasma from DHF vs dengue fever (DF), and informative candidates were selected using nonparametric statistics. These were combined with markers that measure complement activation, acute phase response, cellular leak, granulocyte differentiation and viral load. From this, we applied quantitative proteomics to select a 15 member panel of proteins that accurately predicted DF, DHF, and DFC using a random forest classifier. The classifier primarily relied on acute phase (A2M), complement (CFD), platelet counts and cellular leak (TPM4) to produce an 86% accuracy of prediction with an area under the receiver operating curve of >0.9 for DHF and DFC vs DF. Integrating discovery and heuristic approaches to sample distinct pathophysiological processes is a powerful approach in infectious disease. Early detection of intermediate outcomes of DENV-3 will speed clinical trials evaluating vaccines or drug interventions. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Drug repurposing of minocycline against dengue virus infection.

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    Leela, Shilpa Lekshmi; Srisawat, Chatchawan; Sreekanth, Gopinathan Pillai; Noisakran, Sansanee; Yenchitsomanus, Pa-Thai; Limjindaporn, Thawornchai

    2016-09-09

    Dengue virus infection is one of the most common arthropod-borne viral diseases. A complex interplay between host and viral factors contributes to the severity of infection. The antiviral effects of three antibiotics, lomefloxacin, netilmicin, and minocycline, were examined in this study, and minocycline was found to be a promising drug. This antiviral effect was confirmed in all four serotypes of the virus. The effects of minocycline at various stages of the viral life cycle, such as during viral RNA synthesis, intracellular envelope protein expression, and the production of infectious virions, were examined and found to be significantly reduced by minocycline treatment. Minocycline also modulated host factors, including the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2). The transcription of antiviral genes, including 2'-5'-oligoadenylate synthetase 1 (OAS1), 2'-5'-oligoadenylate synthetase 3 (OAS3), and interferon α (IFNA), was upregulated by minocycline treatment. Therefore, the antiviral activity of minocycline may have a potential clinical use against Dengue virus infection. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. MAIT cells are activated in acute Dengue virus infection and after in vitro Zika virus infection.

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    Dominic Paquin-Proulx

    2018-01-01

    Full Text Available Dengue virus (DENV and Zika virus (ZIKV are members of the Flaviviridae and are predominantly transmitted via mosquito bites. Both viruses are responsible for a growing number of infections in tropical and subtropical regions. DENV infection can cause lethargy with severe morbidity and dengue shock syndrome leading to death in some cases. ZIKV is now linked with Guillain-Barré syndrome and fetal malformations including microcephaly and developmental disorders (congenital Zika syndrome. The protective and pathogenic roles played by the immune response in these infections is unknown. Mucosal-associated invariant T (MAIT cells are a population of innate T cells with potent anti-bacterial activity. MAIT cells have also been postulated to play a role in the immune response to viral infections. In this study, we evaluated MAIT cell frequency, phenotype, and function in samples from subjects with acute and convalescent DENV infection. We found that in acute DENV infection, MAIT cells had elevated co-expression of the activation markers CD38 and HLA-DR and had a poor IFNγ response following bacterial stimulation. Furthermore, we found that MAIT cells can produce IFNγ in response to in vitro infection with ZIKV. This MAIT cell response was independent of MR1, but dependent on IL-12 and IL-18. Our results suggest that MAIT cells may play an important role in the immune response to Flavivirus infections.

  11. Clinical and laboratory features of dengue virus-infected travellers previously vaccinated against yellow fever

    NARCIS (Netherlands)

    Teichmann, Dieter; Göbels, Klaus; Niedrig, Matthias; Grobusch, Martin P.

    2003-01-01

    Dengue is a mosquito-borne viral infection endemic throughout the tropics and subtropics. The global prevalence of dengue has grown dramatically in recent years and it has become a major international public health concern. The close taxonomic relationships between yellow fever and dengue viruses

  12. Infection of Mosquito Cells (C6/36) by Dengue-2 Virus Interferes with Subsequent Infection by Yellow Fever Virus.

    Science.gov (United States)

    Abrao, Emiliana Pereira; da Fonseca, Benedito Antônio Lopes

    2016-02-01

    Dengue is one of the most important diseases caused by arboviruses in the world. Yellow fever is another arthropod-borne disease of great importance to public health that is endemic to tropical regions of Africa and the Americas. Both yellow fever and dengue viruses are flaviviruses transmitted by Aedes aegypti mosquitoes, and then, it is reasonable to consider that in a given moment, mosquito cells could be coinfected by both viruses. Therefore, we decided to evaluate if sequential infections of dengue and yellow fever viruses (and vice-versa) in mosquito cells could affect the virus replication patterns. Using immunofluorescence and real-time PCR-based replication assays in Aedes albopictus C6/36 cells with single or sequential infections with both viruses, we demonstrated the occurrence of viral interference, also called superinfection exclusion, between these two viruses. Our results show that this interference pattern is particularly evident when cells were first infected with dengue virus and subsequently with yellow fever virus (YFV). Reduction in dengue virus replication, although to a lower extent, was also observed when C6/36 cells were initially infected with YFV followed by dengue virus infection. Although the importance that these findings have on nature is unknown, this study provides evidence, at the cellular level, of the occurrence of replication interference between dengue and yellow fever viruses and raises the question if superinfection exclusion could be a possible explanation, at least partially, for the reported lack of urban yellow fever occurrence in regions where a high level of dengue transmission occurs.

  13. An in-depth analysis of original antigenic sin in dengue virus infection.

    Science.gov (United States)

    Midgley, Claire M; Bajwa-Joseph, Martha; Vasanawathana, Sirijitt; Limpitikul, Wannee; Wills, Bridget; Flanagan, Aleksandra; Waiyaiya, Emily; Tran, Hai Bac; Cowper, Alison E; Chotiyarnwong, Pojchong; Chotiyarnwon, Pojchong; Grimes, Jonathan M; Yoksan, Sutee; Malasit, Prida; Simmons, Cameron P; Mongkolsapaya, Juthathip; Screaton, Gavin R

    2011-01-01

    The evolution of dengue viruses has resulted in four antigenically similar yet distinct serotypes. Infection with one serotype likely elicits lifelong immunity to that serotype, but generally not against the other three. Secondary or sequential infections are common, as multiple viral serotypes frequently cocirculate. Dengue infection, although frequently mild, can lead to dengue hemorrhagic fever (DHF) which can be life threatening. DHF is more common in secondary dengue infections, implying a role for the adaptive immune response in the disease. There is currently much effort toward the design and implementation of a dengue vaccine but these efforts are made more difficult by the challenge of inducing durable neutralizing immunity to all four viruses. Domain 3 of the dengue virus envelope protein (ED3) has been suggested as one such candidate because it contains neutralizing epitopes and it was originally thought that relatively few cross-reactive antibodies are directed to this domain. In this study, we performed a detailed analysis of the anti-ED3 response in a cohort of patients suffering either primary or secondary dengue infections. The results show dramatic evidence of original antigenic sin in secondary infections both in terms of binding and enhancement activity. This has important implications for dengue vaccine design because heterologous boosting is likely to maintain the immunological footprint of the first vaccination. On the basis of these findings, we propose a simple in vitro enzyme-linked immunosorbent assay (ELISA) to diagnose the original dengue infection in secondary dengue cases.

  14. Nine year trends of dengue virus infection in Mumbai, Western India.

    Science.gov (United States)

    Shastri, Jayanthi; Williamson, Manita; Vaidya, Nilima; Agrawal, Sachee; Shrivastav, Om

    2017-01-01

    Dengue virus (DENV) causes a wide range of diseases in humans, from acute febrile illness Dengue fever (DF) to life-threatening Dengue hemorrhagic fever (DHF) or Dengue shock syndrome (DSS). Factors believed to be responsible for spread of Dengue virus infection include explosive population growth, unplanned urban overpopulation with inadequate public health systems, poor standing water and vector control, climate changes and increased international recreational, business, military travel to endemic areas. All of these factors must be addressed to control the spread of Dengue and other mosquito-borne infections. The detection of Dengue virus RNA by reverse transcriptase PCR (RT-PCR) in human serum or plasma samples is highly indicative of acute Dengue fever. Moreover, the method is able to identify the Dengue virus serotype by demonstrating defined sequence homologies in the viral genomic RNA. During the nine year period of this study analysis, 6767 strongly suspected cases were tested by RT-PCR. 1685 (24.9%) were Dengue PCR positive and confirmed as Dengue cases. Observations on the seasonality were based on the nine year's data as the intensity of sampling was at its maximum during monsoon season. Dengue typing was done on 100 positive samples after storage of Dengue RNA at - 80°C. Dengue serotypes were detected in 69 samples of which Dengue 2 was most predominant. 576 samples were processed for NS1 antigen and PCR simultaneously. 19/576 were positive (3.3 %) for NS1 as well as by PCR. 23/576 samples were negative for NS1 antigen, but were positive by RT-PCR. The remaining 534 samples which were negative for NS1 antigen were also negative by Dengue RT-PCR. In this study we sought to standardize rapid, sensitive, and specific fluorogenic probe-based RT-PCR assay to screen and serotype a representative range of Dengue viruses that are found in and around Mumbai. Qualitative Dengue virus TaqMan assays could have tremendous utility for the epidemiological

  15. Cross reactivity of commercial anti-dengue immunoassays in patients with acute Zika virus infection.

    Science.gov (United States)

    Felix, Alvina Clara; Souza, Nathalia C Santiago; Figueiredo, Walter M; Costa, Angela A; Inenami, Marta; da Silva, Rosangela M G; Levi, José Eduardo; Pannuti, Claudio Sergio; Romano, Camila Malta

    2017-08-01

    Several countries have local transmission of multiple arboviruses, in particular, dengue and Zika viruses, which have recently spread through many American countries. Cross reactivity among Flaviviruses is high and present a challenge for accurate identification of the infecting agent. Thus, we evaluated the level of cross reactivity of anti-dengue IgM/G Enzyme-Linked Immunosorbent Assays (ELISA) from three manufacturers against 122 serum samples obtained at two time-points from 61 patients with non-dengue confirmed Zika virus infection. All anti-dengue ELISAs cross reacted with serum from patients with acute Zika infection at some level and a worrisome number of seroconversion for dengue IgG and IgM was observed. These findings may impact the interpretation of currently standard criteria for dengue diagnosis in endemic regions. © 2017 Wiley Periodicals, Inc.

  16. Dengue virus infection in renal allograft recipients: a case series during 2010 outbreak.

    Science.gov (United States)

    Prasad, N; Bhadauria, D; Sharma, R K; Gupta, A; Kaul, A; Srivastava, A

    2012-04-01

    Dengue virus infection is an emerging global threat caused by Arbovirus, a virus from Flaviridiae family, which is transmitted by mosquitoes, Aedes aegypti and Aedes albopictus. Renal transplant recipients who live in the endemic zones of dengue infection or who travel to an endemic zone could be at risk of this infection. Despite multiple epidemics and a high case fatality rate in the Southeast Asian region, only a few cases of dengue infection in renal transplant recipients have been reported. Here, we report a case series of 8 dengue viral infection in renal transplant recipients. Of the 8 patients, 3 developed dengue hemorrhagic shock syndrome and died. © 2011 John Wiley & Sons A/S.

  17. Elevated levels of cell-free circulating DNA in patients with acute dengue virus infection.

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    Tran Thi Ngoc Ha

    Full Text Available BACKGROUND: Apoptosis is thought to play a role in the pathogenesis of severe dengue and the release of cell-free DNA into the circulatory system in several medical conditions. Therefore, we investigated circulating DNA as a potential biomarker for severe dengue. METHODS AND FINDINGS: A direct fluorometric degradation assay using PicoGreen was performed to quantify cell-free DNA from patient plasma. Circulating DNA levels were significantly higher in patients with dengue virus infection than with other febrile illnesses and healthy controls. Remarkably, the increase of DNA levels correlated with the severity of dengue. Additionally, multivariate logistic regression analysis showed that circulating DNA levels independently correlated with dengue shock syndrome. CONCLUSIONS: Circulating DNA levels were increased in dengue patients and correlated with dengue severity. Additional studies are required to show the benefits of this biomarker in early dengue diagnosis and for the prognosis of shock complication.

  18. Lack of Durable Cross-Neutralizing Antibodies Against Zika Virus from Dengue Virus Infection.

    Science.gov (United States)

    Collins, Matthew H; McGowan, Eileen; Jadi, Ramesh; Young, Ellen; Lopez, Cesar A; Baric, Ralph S; Lazear, Helen M; de Silva, Aravinda M

    2017-05-01

    Cross-reactive antibodies elicited by dengue virus (DENV) infection might affect Zika virus infection and confound serologic tests. Recent data demonstrate neutralization of Zika virus by monoclonal antibodies or human serum collected early after DENV infection. Whether this finding is true in late DENV convalescence (>6 months after infection) is unknown. We studied late convalescent serum samples from persons with prior DENV or Zika virus exposure. Despite extensive cross-reactivity in IgG binding, Zika virus neutralization was not observed among primary DENV infections. We observed low-frequency (23%) Zika virus cross-neutralization in repeat DENV infections. DENV-immune persons who had Zika virus as a secondary infection had distinct populations of antibodies that neutralized DENVs and Zika virus, as shown by DENV-reactive antibody depletion experiments. These data suggest that most DENV infections do not induce durable, high-level Zika virus cross-neutralizing antibodies. Zika virus-specific antibody populations develop after Zika virus infection irrespective of prior DENV immunity.

  19. Preliminary study of dengue virus infection in Iran

    DEFF Research Database (Denmark)

    Chinikar, Sadegh; Ghiasi, Seyed Mojtaba; Shah-Hosseini, Nariman

    2012-01-01

    Dengue fever is one of the most important arthropod-borne viral diseases of public health significance. It is endemic in most tropical and subtropical parts of the world, many of which are popular tourist destinations. The presence of dengue infection was examined in Iranian patients who were...... abroad. Of these, six cases were from the Sistan and Baluchistan province in southeast Iran and neighbouring Pakistan. Travellers play a key role in the epidemiology of dengue infection in Iran and it is recommended that travellers to endemic areas take precautionary measures to avoid mosquito bites....

  20. High-Throughput Quantitative Proteomic Analysis of Dengue Virus Type 2 Infected A549 Cells

    Science.gov (United States)

    Chiu, Han-Chen; Hannemann, Holger; Heesom, Kate J.; Matthews, David A.; Davidson, Andrew D.

    2014-01-01

    Disease caused by dengue virus is a global health concern with up to 390 million individuals infected annually worldwide. There are no vaccines or antiviral compounds available to either prevent or treat dengue disease which may be fatal. To increase our understanding of the interaction of dengue virus with the host cell, we analyzed changes in the proteome of human A549 cells in response to dengue virus type 2 infection using stable isotope labelling in cell culture (SILAC) in combination with high-throughput mass spectrometry (MS). Mock and infected A549 cells were fractionated into nuclear and cytoplasmic extracts before analysis to identify proteins that redistribute between cellular compartments during infection and reduce the complexity of the analysis. We identified and quantified 3098 and 2115 proteins in the cytoplasmic and nuclear fractions respectively. Proteins that showed a significant alteration in amount during infection were examined using gene enrichment, pathway and network analysis tools. The analyses revealed that dengue virus infection modulated the amounts of proteins involved in the interferon and unfolded protein responses, lipid metabolism and the cell cycle. The SILAC-MS results were validated for a select number of proteins over a time course of infection by Western blotting and immunofluorescence microscopy. Our study demonstrates for the first time the power of SILAC-MS for identifying and quantifying novel changes in cellular protein amounts in response to dengue virus infection. PMID:24671231

  1. High-throughput quantitative proteomic analysis of dengue virus type 2 infected A549 cells.

    Directory of Open Access Journals (Sweden)

    Han-Chen Chiu

    Full Text Available Disease caused by dengue virus is a global health concern with up to 390 million individuals infected annually worldwide. There are no vaccines or antiviral compounds available to either prevent or treat dengue disease which may be fatal. To increase our understanding of the interaction of dengue virus with the host cell, we analyzed changes in the proteome of human A549 cells in response to dengue virus type 2 infection using stable isotope labelling in cell culture (SILAC in combination with high-throughput mass spectrometry (MS. Mock and infected A549 cells were fractionated into nuclear and cytoplasmic extracts before analysis to identify proteins that redistribute between cellular compartments during infection and reduce the complexity of the analysis. We identified and quantified 3098 and 2115 proteins in the cytoplasmic and nuclear fractions respectively. Proteins that showed a significant alteration in amount during infection were examined using gene enrichment, pathway and network analysis tools. The analyses revealed that dengue virus infection modulated the amounts of proteins involved in the interferon and unfolded protein responses, lipid metabolism and the cell cycle. The SILAC-MS results were validated for a select number of proteins over a time course of infection by Western blotting and immunofluorescence microscopy. Our study demonstrates for the first time the power of SILAC-MS for identifying and quantifying novel changes in cellular protein amounts in response to dengue virus infection.

  2. Incidence of dengue virus infection among Japanese travellers, 2006 to 2010

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    Yuki Tada

    2012-06-01

    Full Text Available Introduction: Dengue continues to be a global public health concern. In Japan, although dengue cases are currently seen only among travellers returning from endemic areas, the number of reported cases is rising according to the national case-based surveillance system. We evaluated the characteristics of dengue cases imported into Japan and the relationship between the incidence of infection and season of travel to popular destinations.Methods: Dengue cases reported to the national surveillance system were retrospectively examined. The number of reported cases per number of Japanese travellers to a dengue-endemic country was calculated to estimate the country-specific incidence of imported dengue virus infection. The incidence of dengue infection among Japanese travellers was compared between dengue high season and low season in each country using relative risk (RR and associated 95% confidence intervals (CI.Results: Among 540 Japanese residents who were reported as dengue cases from 2006 to 2010, the majority had travelled to Indonesia, India, the Philippines and Thailand. The RR of dengue infection among Japanese travellers during dengue high season versus low season was 4.92 (95% CI: 3.01–8.04 for the Philippines, 2.76 (95% CI: 1.67–4.54 for Thailand and 0.37 (95% CI: 0.15–0.92 for Indonesia.Discussion: Overall, higher incidence of imported cases appeared to be related to historic dengue high seasons. Travellers planning to visit dengue-endemic countries should be aware of historic dengue seasonality and the current dengue situation.

  3. Dengue viral infections

    OpenAIRE

    Gurugama Padmalal; Garg Pankaj; Perera Jennifer; Wijewickrama Ananda; Seneviratne Suranjith

    2010-01-01

    Dengue viral infections are one of the most important mosquito-borne diseases in the world. Presently dengue is endemic in 112 countries in the world. It has been estimated that almost 100 million cases of dengue fever and half a million cases of dengue hemorrhagic fever (DHF) occur worldwide. An increasing proportion of DHF is in children less than 15 years of age, especially in South East and South Asia. The unique structure of the dengue virus and the pathophysiologic responses of the host...

  4. Factors contributing to the disturbance of coagulation and fibrinolysis in dengue virus infection

    Directory of Open Access Journals (Sweden)

    Yung-Chun Chuang

    2013-01-01

    Full Text Available Hemorrhage is one of the hallmarks of dengue hemorrhagic fever. However, the mechanisms that cause hemorrhage are unclear. In this review we focus on the possible factors that may be involved in the disturbance of coagulation and fibrinolysis during dengue virus (DENV infection. Factors such as autoantibodies and cytokines induced by DENV infection as well as hemostatic molecules expressed on DENV-infected cells, and DENV viral proteins may all contribute to the defect of hemostasis during DENV infection. It is the combination of these viral and host factors that may tilt the balance of coagulation and fibrinolysis toward bleeding in dengue patients.

  5. Susceptibility and response of human blood monocyte subsets to primary dengue virus infection.

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    Kok Loon Wong

    Full Text Available Human blood monocytes play a central role in dengue infections and form the majority of virus infected cells in the blood. Human blood monocytes are heterogeneous and divided into CD16(- and CD16(+ subsets. Monocyte subsets play distinct roles during disease, but it is not currently known if monocyte subsets differentially contribute to dengue protection and pathogenesis. Here, we compared the susceptibility and response of the human CD16(- and CD16(+ blood monocyte subsets to primary dengue virus in vitro. We found that both monocyte subsets were equally susceptible to dengue virus (DENV2 NGC, and capable of supporting the initial production of new infective virus particles. Both monocyte subsets produced anti-viral factors, including IFN-α, CXCL10 and TRAIL. However, CD16(+ monocytes were the major producers of inflammatory cytokines and chemokines in response to dengue virus, including IL-1β, TNF-α, IL-6, CCL2, 3 and 4. The susceptibility of both monocyte subsets to infection was increased after IL-4 treatment, but this increase was more profound for the CD16(+ monocyte subset, particularly at early time points after virus exposure. These findings reveal the differential role that monocyte subsets might play during dengue disease.

  6. Morphological studies in a model for dengue-2 virus infection in mice

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    Ortrud Monika Barth

    2006-12-01

    Full Text Available One of the main difficulties in studying dengue virus infection in humans and in developing a vaccine is the absence of a suitable animal model which develops the full spectrum of dengue fever, dengue haemorrhagic fever, and dengue shock syndrome. It is our proposal to present morphological aspects of an animal model which shows many similarities with the dengue infection in humans. BALB/c mice were intraperitoneally infected with non-neuroadapted dengue virus serotype 2 (DENV-2. Histopathological and morphometrical analyses of liver tissue revealed focal alterations along the infection, reaching wide-ranging portal and centrolobular veins congestion and sinusoidal cell death. Additional ultrastructural observations demonstrated multifocal endothelial injury, platelet recruitment, and alterated hepatocytes. Dengue virus antigen was detected in hepatocytes and in the capillar endothelium of the central lobular vein area. Liver function tests showed high levels of aspartate transaminase and alanine transaminase enzyme activity. Lung tissue showed interstitial pneumonia and mononuclear cells, interseptal oedema, hyperplasia, and hypertrophy of the bronchiolar epithelial cells. DENV-2 led to a transient inflammatory process, but caused focal alterations of the blood-exchange barrier. Viremia was observed from 2nd to 11th day p.i. by isolation of DENV-2 in C6/36 mosquito cell line inoculated with the supernatant of macerated liver, lung, kidney, and cerebellum tissues of the infected mice.

  7. Optical diagnosis of dengue virus infection in human blood serum using Raman spectroscopy

    International Nuclear Information System (INIS)

    Saleem, M; Bilal, M; Anwar, S; Rehman, A; Ahmed, M

    2013-01-01

    We present the optical diagnosis of dengue virus infection in human blood serum using Raman spectroscopy. Raman spectra were acquired from 18 blood serum samples using a laser at 532 nm as the excitation source. A multivariate regression model based on partial least-squares regression is developed that uses Raman spectra to predict dengue infection with leave-one-sample-out cross validation. The prediction of dengue infection by our model yields correlation coefficient r 2 values of 0.9998 between the predicted and reference clinical results. The model was tested for six unknown human blood sera and found to be 100% accurate in accordance with the clinical results. (letter)

  8. Dengue virus activates polyreactive, natural IgG B cells after primary and secondary infection.

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    Thavamalar Balakrishnan

    Full Text Available BACKGROUND: Dengue virus is transmitted by mosquitoes and has four serotypes. Cross-protection to other serotypes lasting for a few months is observed following infection with one serotype. There is evidence that low-affinity T and/or B cells from primary infections contribute to the severe syndromes often associated with secondary dengue infections. such pronounced immune-mediated enhancement suggests a dengue-specific pattern of immune cell activation. This study investigates the acute and early convalescent B cell response leading to the generation of cross-reactive and neutralizing antibodies following dengue infection. METHODOLOGY/PRINCIPAL FINDINGS: We assayed blood samples taken from dengue patients with primary or secondary infection during acute disease and convalescence and compared them to samples from patients presenting with non-dengue related fever. Dengue induced massive early plasmablast formation, which correlated with the appearance of polyclonal, cross-reactive IgG for both primary and secondary infection. Surprisingly, the contribution of IgG to the neutralizing titer 4-7 days after fever onset was more than 50% even after primary infection. CONCLUSIONS/SIGNIFICANCE: Poly-reactive and virus serotype cross-reactive IgG are an important component of the innate response in humans during both primary and secondary dengue infection, and "innate specificities" seem to constitute part of the adaptive response in dengue. While of potential importance for protection during secondary infection, cross-reactive B cells will also compete with highly neutralizing B cells and possibly interfere with their development.

  9. Serum Metabolomics Investigation of Humanized Mouse Model of Dengue Virus Infection.

    Science.gov (United States)

    Cui, Liang; Hou, Jue; Fang, Jinling; Lee, Yie Hou; Costa, Vivian Vasconcelos; Wong, Lan Hiong; Chen, Qingfeng; Ooi, Eng Eong; Tannenbaum, Steven R; Chen, Jianzhu; Ong, Choon Nam

    2017-07-15

    Dengue is an acute febrile illness caused by dengue virus (DENV) and a major cause of morbidity and mortality in tropical and subtropical regions of the world. The lack of an appropriate small-animal model of dengue infection has greatly hindered the study of dengue pathogenesis and the development of therapeutics. In this study, we conducted mass spectrometry-based serum metabolic profiling from a model using humanized mice (humice) with DENV serotype 2 infection at 0, 3, 7, 14, and 28 days postinfection (dpi). Forty-eight differential metabolites were identified, including fatty acids, purines and pyrimidines, acylcarnitines, acylglycines, phospholipids, sphingolipids, amino acids and derivatives, free fatty acids, and bile acid. These metabolites showed a reversible-change trend-most were significantly perturbed at 3 or 7 dpi and returned to control levels at 14 or 28 dpi, indicating that the metabolites might serve as prognostic markers of the disease in humice. The major perturbed metabolic pathways included purine and pyrimidine metabolism, fatty acid β-oxidation, phospholipid catabolism, arachidonic acid and linoleic acid metabolism, sphingolipid metabolism, tryptophan metabolism, phenylalanine metabolism, lysine biosynthesis and degradation, and bile acid biosynthesis. Most of these disturbed pathways are similar to our previous metabolomics findings in a longitudinal cohort of adult human dengue patients across different infection stages. Our analyses revealed the commonalities of host responses to DENV infection between humice and humans and suggested that humice could be a useful small-animal model for the study of dengue pathogenesis and the development of dengue therapeutics. IMPORTANCE Dengue virus is the most widespread arbovirus, causing an estimated 390 million dengue infections worldwide every year. There is currently no effective treatment for the disease, and the lack of an appropriate small-animal model of dengue infection has greatly

  10. Wolbachia and dengue virus infection in the mosquito Aedes fluviatilis (Diptera: Culicidae.

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    Jéssica Barreto Lopes Silva

    Full Text Available Dengue represents a serious threat to human health, with billions of people living at risk of the disease. Wolbachia pipientis is a bacterial endosymbiont common to many insect species. Wolbachia transinfections in mosquito disease vectors have great value for disease control given the bacterium's ability to spread into wild mosquito populations, and to interfere with infections of pathogens, such as dengue virus. Aedes fluviatilis is a mosquito with a widespread distribution in Latin America, but its status as a dengue vector has not been clarified. Ae. fluviatilis is also naturally infected by the wFlu Wolbachia strain, which has been demonstrated to enhance infection with the avian malarial parasite Plasmodium gallinaceum. We performed experimental infections of Ae. fluviatilis with DENV-2 and DENV-3 isolates from Brazil via injection or oral feeding to provide insight into its competence for the virus. We also examined the effect of the native Wolbachia infection on the virus using a mosquito line where the wFlu infection had been cleared by antibiotic treatment. Through RT-qPCR, we observed that Ae. fluviatilis could become infected with both viruses via either method of infection, although at a lower rate than Aedes aegypti, the primary dengue vector. We then detected DENV-2 and DENV-3 in the saliva of injected mosquitoes, and observed that injection of DENV-3-infected saliva produced subsequent infections in naïve Ae. aegypti. However, across our data we observed no difference in prevalence of infection and viral load between Wolbachia-infected and -uninfected mosquitoes, suggesting that there is no effect of wFlu on dengue virus. Our results highlight that Ae. fluviatilis could potentially serve as a dengue vector under the right circumstances, although further testing is required to determine if this occurs in the field.

  11. Co-circulation and co-infections of all dengue virus serotypes in Hyderabad, India 2014.

    Science.gov (United States)

    Vaddadi, K; Gandikota, C; Jain, P K; Prasad, V S V; Venkataramana, M

    2017-09-01

    The burden of dengue virus infections increased globally during recent years. Though India is considered as dengue hyper-endemic country, limited data are available on disease epidemiology. The present study includes molecular characterization of dengue virus strains occurred in Hyderabad, India, during the year 2014. A total of 120 febrile cases were recruited for this study, which includes only children and 41 were serologically confirmed for dengue positive infections using non-structural (NS1) and/or IgG/IgM ELISA tests. RT-PCR, nucleotide sequencing and evolutionary analyses were carried out to identify the circulating serotypes/genotypes. The data indicated a high percent of severe dengue (63%) in primary infections. Simultaneous circulation of all four serotypes and co-infections were observed for the first time in Hyderabad, India. In total, 15 patients were co-infected with more than one dengue serotype and 12 (80%) of them had severe dengue. One of the striking findings of the present study is the identification of serotype Den-1 as the first report from this region and this strain showed close relatedness to the Thailand 1980 strains but not to any of the strains reported from India until now. Phylogenetically, all four strains of the present study showed close relatedness to the strains, which are reported to be high virulent.

  12. Neurological Manifestations of Dengue Infection

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    Guo-Hong Li

    2017-10-01

    Full Text Available Dengue counts among the most commonly encountered arboviral diseases, representing the fastest spreading tropical illness in the world. It is prevalent in 128 countries, and each year >2.5 billion people are at risk of dengue virus infection worldwide. Neurological signs of dengue infection are increasingly reported. In this review, the main neurological complications of dengue virus infection, such as central nervous system (CNS, peripheral nervous system, and ophthalmic complications were discussed according to clinical features, treatment and possible pathogenesis. In addition, neurological complications in children were assessed due to their atypical clinical features. Finally, dengue infection and Japanese encephalitis were compared for pathogenesis and main clinical manifestations.

  13. Molecular mechanisms of dengue virus infection : cell tropism, antibody-dependent enhancement, and cytokines

    NARCIS (Netherlands)

    Flipse, Jacobus

    2015-01-01

    Dengue is the most prevalent mosquito-borne viral disease in humans. Although most infections occur in the (sub)tropical areas, recent outbreaks in Italy and Madeira indicate that the virus is spreading into Europe. Despite its relevance, no vaccine or medications are available against this virus.

  14. Mitochondrial and bioenergetic dysfunction in human hepatic cells infected with dengue 2 virus

    OpenAIRE

    El-Bacha , Tatiana; Midlej , Victor; Silva , Ana Paula Pereira Da; Costa , Leandro Silva Da; Benchimol , Marlene; Galina , Antonio; Poian , Andrea T. Da

    2007-01-01

    Mitochondrial and bioenergetic dysfunction in human hepatic cells infected with dengue 2 virus correspondence: Corresponding author. Fax: +55 21 22708647. (El-Bacha, Tatiana) (El-Bacha, Tatiana) Laboratorio de Bioquimica de Virus, Instituto de Bioquimica Medica, Universidade Federal do Rio de Janeiro - RJ-Brasil--> , Av. Bauhinia n? 400 ? CCS Bloco H 2? andar--> , sala 22. Ilha do Governador--> ...

  15. Pathogenesis of vascular leak in dengue virus infection.

    Science.gov (United States)

    Malavige, Gathsaurie Neelika; Ogg, Graham S

    2017-07-01

    Endothelial dysfunction leading to vascular leak is the hallmark of severe dengue. Vascular leak typically becomes clinically evident 3-6 days after the onset of illness, which is known as the critical phase. This critical phase follows the period of peak viraemia, and lasts for 24-48 hr and usually shows rapid and complete reversal, suggesting that it is likely to occur as a result of inflammatory mediators, rather than infection of the endothelium. Cytokines such as tumour necrosis factor-α, which are known to be elevated in the critical phase of dengue, are likely to be contributing factors. Dengue NS1, a soluble viral protein, has also been shown to disrupt the endothelial glycocalyx and thus contribute to vascular leak, although there appears to be a discordance between the timing of NS1 antigenaemia and occurrence of vascular leak. In addition, many inflammatory lipid mediators are elevated in acute dengue viral infection such as platelet activating factor (PAF) and leukotrienes. Furthermore, many other inflammatory mediators such as vascular endothelial growth factor and angiopoietin-2 have been shown to be elevated in patients with dengue haemorrhagic fever, exerting their action in part by inducing the activity of phospholipases, which have diverse inflammatory effects including generation of PAF. Platelets have also been shown to significantly contribute to endothelial dysfunction by production of interleukin-1β through activation of the NLRP3 inflammasome and also by inducing production of inflammatory cytokines by monocytes. Drugs that block down-stream immunological mediator pathways such as PAF may also be beneficial in the treatment of severe disease. © 2017 John Wiley & Sons Ltd.

  16. Dengue viral infections

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    Gurugama Padmalal

    2010-01-01

    Full Text Available Dengue viral infections are one of the most important mosquito-borne diseases in the world. Presently dengue is endemic in 112 countries in the world. It has been estimated that almost 100 million cases of dengue fever and half a million cases of dengue hemorrhagic fever (DHF occur worldwide. An increasing proportion of DHF is in children less than 15 years of age, especially in South East and South Asia. The unique structure of the dengue virus and the pathophysiologic responses of the host, different serotypes, and favorable conditions for vector breeding have led to the virulence and spread of the infections. The manifestations of dengue infections are protean from being asymptomatic to undifferentiated fever, severe dengue infections, and unusual complications. Early recognition and prompt initiation of appropriate supportive treatment are often delayed resulting in unnecessarily high morbidity and mortality. Attempts are underway for the development of a vaccine for preventing the burden of this neglected disease. This review outlines the epidemiology, clinical features, pathophysiologic mechanisms, management, and control of dengue infections.

  17. Sophoraflavenone G Restricts Dengue and Zika Virus Infection via RNA Polymerase Interference.

    Science.gov (United States)

    Sze, Alexandre; Olagnier, David; Hadj, Samar Bel; Han, Xiaoying; Tian, Xiao Hong; Xu, Hong-Tao; Yang, Long; Shi, Qingwen; Wang, Penghua; Wainberg, Mark A; Wu, Jian Hui; Lin, Rongtuan

    2017-10-03

    Flaviviruses including Zika, Dengue and Hepatitis C virus cause debilitating diseases in humans, and the former are emerging as global health concerns with no antiviral treatments. We investigated Sophora Flavecens , used in Chinese medicine, as a source for antiviral compounds. We isolated Sophoraflavenone G and found that it inhibited Hepatitis C replication, but not Sendai or Vesicular Stomatitis Virus. Pre- and post-infection treatments demonstrated anti-flaviviral activity against Dengue and Zika virus, via viral RNA polymerase inhibition. These data suggest that Sophoraflavenone G represents a promising candidate regarding anti-Flaviviridae research.

  18. Clinical Features and Laboratory Findings of Travelers Returning to South Australia with Dengue Virus Infection

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    Emma J. Quinn

    2018-01-01

    Full Text Available Reported cases of dengue are rising in South Australia (SA in travellers returning from dengue-endemic regions. We have undertaken a retrospective analysis to identify the clinical and laboratory characteristics of patients returning to SA with suspected dengue virus (DENV infection. From 488 requests, 49 (10% were defined by serology as acute dengue, with the majority of patients (75% testing as non-structural protein 1 (NS1 and/or IgM positive. Dengue was most commonly acquired in Indonesia (42.9% with clinical features of fever (95%, headache (41% and myalgia/arthralgia (56%. The presence of rash (36% and laboratory findings of neutropenia, leukopenia, thrombocytopenia, but not elevated C-reactive protein, were distinct from findings in DENV-seronegative patients. Available dengue seropositive samples were analysed by RT-PCR, with 14/32 (43.8% positive by a serotype non-specific DENV assay, but 28/32 positive (87.5% when also assessed by serotype-specific RT-PCR. Serotype analysis revealed the predominance of DENV-1 and DENV-2 and the presence of DENV-3, but not DENV-4 or Zika virus (ZIKV. Thus, dengue in returned travellers in SA presents in a manner consistent with World Health Organization (WHO definitions, with symptoms, travel history and laboratory results useful in prioritising the likelihood of dengue. This definition will assist the future management in DENV-non-endemic regions, such as SA.

  19. Dengue virus receptor

    OpenAIRE

    Hidari, Kazuya I.P.J.; Suzuki, Takashi

    2011-01-01

    Dengue virus is an arthropod-borne virus transmitted by Aedes mosquitoes. Dengue virus causes fever and hemorrhagic disorders in humans and non-human primates. Direct interaction of the virus introduced by a mosquito bite with host receptor molecule(s) is crucial for virus propagation and the pathological progression of dengue diseases. Therefore, elucidation of the molecular mechanisms underlying the interaction between dengue virus and its receptor(s) in both humans and mosquitoes is essent...

  20. Dendritic cells in dengue virus infection: Targets of virus replication and mediators of immunity

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    Michael A. Schmid

    2014-12-01

    Full Text Available Dendritic cells (DCs are sentinels of the immune system and detect pathogens at sites of entry, such as the skin. In addition to the ability of DCs to control infections directly via their innate immune functions, DCs help to prime adaptive B and T cell responses via antigen presentation in lymphoid tissues. Infected Aedes aegypti or Ae. albopictus mosquitoes transmit the four dengue virus (DENV serotypes to humans while probing for small blood vessels in the skin. DENV causes the most prevalent arthropod-borne viral disease in humans, yet no vaccine or specific therapeutic is currently approved. Although primary DENV infection confers life-long protective immunity against re-infection with the same DENV serotype, secondary infection with a different DENV serotype can lead to increased disease severity via cross-reactive T cells or enhancing antibodies. This review summarizes recent findings in humans and animal models about DENV infection of DCs, monocytes and macrophages. We discuss the dual role of DCs as both targets of DENV replication and mediators of innate and adaptive immunity, and summarize immune evasion strategies whereby DENV impairs the function of infected DCs. We suggest that DCs play a key role in priming DENV-specific neutralizing or potentially harmful memory B and T cell responses, and that future DC-directed therapies may help induce protective memory responses and reduce dengue pathogenesis.

  1. A DNA Microarray-Based Assay to Detect Dual Infection with Two Dengue Virus Serotypes

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    Alvaro Díaz-Badillo

    2014-04-01

    Full Text Available Here; we have described and tested a microarray based-method for the screening of dengue virus (DENV serotypes. This DNA microarray assay is specific and sensitive and can detect dual infections with two dengue virus serotypes and single-serotype infections. Other methodologies may underestimate samples containing more than one serotype. This technology can be used to discriminate between the four DENV serotypes. Single-stranded DNA targets were covalently attached to glass slides and hybridised with specific labelled probes. DENV isolates and dengue samples were used to evaluate microarray performance. Our results demonstrate that the probes hybridized specifically to DENV serotypes; with no detection of unspecific signals. This finding provides evidence that specific probes can effectively identify single and double infections in DENV samples.

  2. The seroprevalence and seroincidence of dengue virus infection in western Kenya.

    Science.gov (United States)

    Blaylock, Jason M; Maranich, Ashley; Bauer, Kristen; Nyakoe, Nancy; Waitumbi, John; Martinez, Luis J; Lynch, Julia

    2011-09-01

    Epidemics of dengue fever have been documented throughout the African continent over the past several decades, however little is known about the prevalence or incidence of dengue virus infection in the absence of an outbreak. No studies have analyzed the prevalence of dengue infection in western Kenya to date. This study describes the seroincidence and seroprevalence of dengue infection in western Kenya. Banked sera obtained from 354 healthy, afebrile children ages 12-47 months from Kisumu District, Kenya, were analyzed for antibodies to dengue virus using an IgG indirect ELISA. We found a seroprevalence of 1.1% (4 of 354 samples) and incidence of 8.5 seroconversions per 1000 persons per year in this study population. This appears to be similar to that previously reported in coastal regions of the country outside of known epidemic periods. Since there has never been a reported dengue epidemic in western Kenya, continued investigation and evaluation in a patient population presenting with fever is necessary to further confirm this finding. Published by Elsevier Ltd.

  3. The Epidemiology, Virology and Clinical Findings of Dengue Virus Infections in a Cohort of Indonesian Adults in Western Java.

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    Herman Kosasih

    2016-02-01

    Full Text Available Dengue has emerged as one of the most important infectious diseases in the last five decades. Evidence indicates the expansion of dengue virus endemic areas and consequently the exponential increase of dengue virus infections across the subtropics. The clinical manifestations of dengue virus infection include sudden fever, rash, headache, myalgia and in more serious cases, spontaneous bleeding. These manifestations occur in children as well as in adults. Defining the epidemiology of dengue in a given area is critical to understanding the disease and devising effective public health strategies.Here, we report the results from a prospective cohort study of 4380 adults in West Java, Indonesia, from 2000-2004 and 2006-2009. A total of 2167 febrile episodes were documented and dengue virus infections were confirmed by RT-PCR or serology in 268 cases (12.4%. The proportion ranged from 7.6 to 41.8% each year. The overall incidence rate of symptomatic dengue virus infections was 17.3 cases/1,000 person years and between September 2006 and April 2008 asymptomatic infections were 2.6 times more frequent than symptomatic infections. According to the 1997 WHO classification guidelines, there were 210 dengue fever cases, 53 dengue hemorrhagic fever cases (including one dengue shock syndrome case and five unclassified cases. Evidence for sequential dengue virus infections was seen in six subjects. All four dengue virus serotypes circulated most years. Inapparent dengue virus infections were predominantly associated with DENV-4 infections.Dengue virus was responsible for a significant percentage of febrile illnesses in an adult population in West Java, Indonesia, and this percentage varied from year to year. The observed incidence rate during the study period was 43 times higher than the reported national or provincial rates during the same time period. A wide range of clinical severity was observed with most infections resulting in asymptomatic disease. The

  4. Differential Gene Expression Changes in Children with Severe Dengue Virus Infections

    NARCIS (Netherlands)

    de Kruif, Martijn D.; Setiati, Tatty E.; Mairuhu, Albertus T. A.; Koraka, Penelopie; Aberson, Hella A.; Spek, C. Arnold; Osterhaus, Albert D. M. E.; Reitsma, Pieter H.; Brandjes, Dees P. M.; Soemantri, Augustinus; van Gorp, Eric C. M.

    2008-01-01

    Background: The host response to dengue virus infection is characterized by the production of numerous cytokines, but the overall picture appears to be complex. It has been suggested that a balance may be involved between protective and pathologic immune responses. This study aimed to define

  5. Antibody-dependent enhancement of dengue virus infection is inhibited by SA-17, a doxorubicin derivative

    NARCIS (Netherlands)

    Ayala Nunez, Vanesa; Jarupathirun, Patsaporn; Kaptein, Suzanne; Neyts, Johan; Smit, Jolanda

    2013-01-01

    Antibody-dependent enhancement (ADE) is thought to play a critical role in the exacerbation of dengue virus (DENV)-induced disease during a heterologous re-infection. Despite ADE's clinical impact, only a few antiviral compounds have been assessed for their anti-ADE activity. We reported earlier

  6. Complex modulation of the Aedes aegypti transcriptome in response to dengue virus infection.

    Science.gov (United States)

    Bonizzoni, Mariangela; Dunn, W Augustine; Campbell, Corey L; Olson, Ken E; Marinotti, Osvaldo; James, Anthony A

    2012-01-01

    Dengue fever is the most important arboviral disease world-wide, with Aedes aegypti being the major vector. Interactions between the mosquito host and dengue viruses (DENV) are complex and vector competence varies among geographically-distinct Ae. aegypti populations. Additionally, dengue is caused by four antigenically-distinct viral serotypes (DENV1-4), each with multiple genotypes. Each virus genotype interacts differently with vertebrate and invertebrate hosts. Analyses of alterations in mosquito transcriptional profiles during DENV infection are expected to provide the basis for identifying networks of genes involved in responses to viruses and contribute to the molecular-genetic understanding of vector competence. In addition, this knowledge is anticipated to support the development of novel disease-control strategies. RNA-seq technology was used to assess genome-wide changes in transcript abundance at 1, 4 and 14 days following DENV2 infection in carcasses, midguts and salivary glands of the Ae. aegypti Chetumal strain. DENV2 affected the expression of 397 Ae. aegypti genes, most of which were down-regulated by viral infection. Differential accumulation of transcripts was mainly tissue- and time-specific. Comparisons of our data with other published reports reveal conservation of functional classes, but limited concordance of specific mosquito genes responsive to DENV2 infection. These results indicate the necessity of additional studies of mosquito-DENV interactions, specifically those focused on recently-derived mosquito strains with multiple dengue virus serotypes and genotypes.

  7. Complex modulation of the Aedes aegypti transcriptome in response to dengue virus infection.

    Directory of Open Access Journals (Sweden)

    Mariangela Bonizzoni

    Full Text Available Dengue fever is the most important arboviral disease world-wide, with Aedes aegypti being the major vector. Interactions between the mosquito host and dengue viruses (DENV are complex and vector competence varies among geographically-distinct Ae. aegypti populations. Additionally, dengue is caused by four antigenically-distinct viral serotypes (DENV1-4, each with multiple genotypes. Each virus genotype interacts differently with vertebrate and invertebrate hosts. Analyses of alterations in mosquito transcriptional profiles during DENV infection are expected to provide the basis for identifying networks of genes involved in responses to viruses and contribute to the molecular-genetic understanding of vector competence. In addition, this knowledge is anticipated to support the development of novel disease-control strategies. RNA-seq technology was used to assess genome-wide changes in transcript abundance at 1, 4 and 14 days following DENV2 infection in carcasses, midguts and salivary glands of the Ae. aegypti Chetumal strain. DENV2 affected the expression of 397 Ae. aegypti genes, most of which were down-regulated by viral infection. Differential accumulation of transcripts was mainly tissue- and time-specific. Comparisons of our data with other published reports reveal conservation of functional classes, but limited concordance of specific mosquito genes responsive to DENV2 infection. These results indicate the necessity of additional studies of mosquito-DENV interactions, specifically those focused on recently-derived mosquito strains with multiple dengue virus serotypes and genotypes.

  8. Detection of immune-complex-dissociated nonstructural-1 antigen in patients with acute dengue virus infections

    NARCIS (Netherlands)

    P. Koraka (Penelope); C.P. Burghoorn-Maas; A. Falconar; T.E. Setiati (Tatty); K. Djamiatun; J. Groen (Jan); A.D.M.E. Osterhaus (Albert)

    2003-01-01

    textabstractAccurate and timely diagnosis of dengue virus (DEN) infections is essential for the differential diagnosis of patients with febrile illness and hemorrhagic fever. In the present study, the diagnostic value of a newly developed immune-complex dissociated nonstructural-1 (NS-1) antigen dot

  9. Detection of immune-complex-dissociated nonstructural-1 antigen in patients with acute dengue virus infections.

    NARCIS (Netherlands)

    Koraka, P.; Burghoorn-Maas, C.P.; Falconar, A.; Setiati, T.E.; Djamiatun, K.; Groen, J.; Osterhaus, A.D.

    2003-01-01

    Accurate and timely diagnosis of dengue virus (DEN) infections is essential for the differential diagnosis of patients with febrile illness and hemorrhagic fever. In the present study, the diagnostic value of a newly developed immune-complex dissociated nonstructural-1 (NS-1) antigen dot blot

  10. Suppression of chikungunya virus replication and differential innate responses of human peripheral blood mononuclear cells during co-infection with dengue virus

    NARCIS (Netherlands)

    Silva, Mariana Ruiz; Briseno, Jose A. Aguilar; Upasani, Vinit; van der Ende-Metselaar, Heidi; Smit, Jolanda M.; Rodenhuis-Zybert, Izabela A.

    2017-01-01

    Dengue and chikungunya are viral diseases transmitted to humans by infected Aedes spp. mosquitoes. With an estimated 390 million infected people per year dengue virus (DENV) currently causes the most prevalent arboviral disease. During the last decade chikungunya virus (CHIKV) has caused large

  11. Therapeutic Effects of Monoclonal Antibody against Dengue Virus NS1 in a STAT1 Knockout Mouse Model of Dengue Infection.

    Science.gov (United States)

    Wan, Shu-Wen; Chen, Pei-Wei; Chen, Chin-Yu; Lai, Yen-Chung; Chu, Ya-Ting; Hung, Chia-Yi; Lee, Han; Wu, Hsuan Franziska; Chuang, Yung-Chun; Lin, Jessica; Chang, Chih-Peng; Wang, Shuying; Liu, Ching-Chuan; Ho, Tzong-Shiann; Lin, Chiou-Feng; Lee, Chien-Kuo; Wu-Hsieh, Betty A; Anderson, Robert; Yeh, Trai-Ming; Lin, Yee-Shin

    2017-10-15

    Dengue virus (DENV) is the causative agent of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome and is endemic to tropical and subtropical regions of the world. Our previous studies showed the existence of epitopes in the C-terminal region of DENV nonstructural protein 1 (NS1) which are cross-reactive with host Ags and trigger anti-DENV NS1 Ab-mediated endothelial cell damage and platelet dysfunction. To circumvent these potentially harmful events, we replaced the C-terminal region of DENV NS1 with the corresponding region from Japanese encephalitis virus NS1 to create chimeric DJ NS1 protein. Passive immunization of DENV-infected mice with polyclonal anti-DJ NS1 Abs reduced viral Ag expression at skin inoculation sites and shortened DENV-induced prolonged bleeding time. We also investigated the therapeutic effects of anti-NS1 mAb. One mAb designated 2E8 does not recognize the C-terminal region of DENV NS1 in which host-cross-reactive epitopes reside. Moreover, mAb 2E8 recognizes NS1 of all four DENV serotypes. We also found that mAb 2E8 caused complement-mediated lysis in DENV-infected cells. In mouse model studies, treatment with mAb 2E8 shortened DENV-induced prolonged bleeding time and reduced viral Ag expression in the skin. Importantly, mAb 2E8 provided therapeutic effects against all four serotypes of DENV. We further found that mAb administration to mice as late as 1 d prior to severe bleeding still reduced prolonged bleeding time and hemorrhage. Therefore, administration with a single dose of mAb 2E8 can protect mice against DENV infection and pathological effects, suggesting that NS1-specific mAb may be a therapeutic option against dengue disease. Copyright © 2017 by The American Association of Immunologists, Inc.

  12. Dengue virus type 2 infections of Aedes aegypti are modulated by the mosquito's RNA interference pathway.

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    Irma Sánchez-Vargas

    2009-02-01

    Full Text Available A number of studies have shown that both innate and adaptive immune defense mechanisms greatly influence the course of human dengue virus (DENV infections, but little is known about the innate immune response of the mosquito vector Aedes aegypti to arbovirus infection. We present evidence here that a major component of the mosquito innate immune response, RNA interference (RNAi, is an important modulator of mosquito infections. The RNAi response is triggered by double-stranded RNA (dsRNA, which occurs in the cytoplasm as a result of positive-sense RNA virus infection, leading to production of small interfering RNAs (siRNAs. These siRNAs are instrumental in degradation of viral mRNA with sequence homology to the dsRNA trigger and thereby inhibition of virus replication. We show that although dengue virus type 2 (DENV2 infection of Ae. aegypti cultured cells and oral infection of adult mosquitoes generated dsRNA and production of DENV2-specific siRNAs, virus replication and release of infectious virus persisted, suggesting viral circumvention of RNAi. We also show that DENV2 does not completely evade RNAi, since impairing the pathway by silencing expression of dcr2, r2d2, or ago2, genes encoding important sensor and effector proteins in the RNAi pathway, increased virus replication in the vector and decreased the extrinsic incubation period required for virus transmission. Our findings indicate a major role for RNAi as a determinant of DENV transmission by Ae. aegypti.

  13. Competitive advantage of a dengue 4 virus when co-infecting the mosquito Aedes aegypti with a dengue 1 virus.

    Science.gov (United States)

    Vazeille, Marie; Gaborit, Pascal; Mousson, Laurence; Girod, Romain; Failloux, Anna-Bella

    2016-07-08

    Dengue viruses (DENV) are comprised in four related serotypes (DENV-1 to 4) and are critically important arboviral pathogens affecting human populations in the tropics. South American countries have seen the reemergence of DENV since the 1970's associated with the progressive re-infestation by the mosquito vector, Aedes aegypti. In French Guiana, DENV is now endemic with the co-circulation of different serotypes resulting in viral epidemics. Between 2009 and 2010, a predominant serotype change occurred from DENV-1 to DENV-4 suggesting a competitive displacement. The aim of the present study was to evaluate the potential role of the mosquito in the selection of the new epidemic serotype. To test this hypothesis of competitive displacement of one serotype by another in the mosquito vector, we performed mono- and co-infections of local Ae. aegypti collected during the inter-epidemic period with both viral autochthonous epidemic serotypes and compared infection, dissemination and transmission rates. We performed oral artificial infections of F1 populations in BSL-3 conditions and analyzed infection, dissemination and transmission rates. When two populations of Ae. aegypti from French Guiana were infected with either serotype, no significant differences in dissemination and transmission were observed between DENV-1 and DENV-4. However, in co-infection experiments, a strong competitive advantage for DENV-4 was seen at the midgut level leading to a much higher dissemination of this serotype. Furthermore only DENV-4 was present in Ae. aegypti saliva and therefore able to be transmitted. In an endemic context, mosquito vectors may be infected by several DENV serotypes. Our results suggest a possible competition between serotypes at the midgut level in co-infected mosquitoes leading to a drastically different transmission potential and, in this case, favoring the competitive displacement of DENV-1 by DENV-4. This phenomenon was observed despite a similar replicative fitness

  14. Activation of peripheral blood mononuclear cells by dengue virus infection depotentiates balapiravir.

    Science.gov (United States)

    Chen, Yen-Liang; Abdul Ghafar, Nahdiyah; Karuna, Ratna; Fu, Yilong; Lim, Siew Pheng; Schul, Wouter; Gu, Feng; Herve, Maxime; Yokohama, Fumiaki; Wang, Gang; Cerny, Daniela; Fink, Katja; Blasco, Francesca; Shi, Pei-Yong

    2014-02-01

    In a recent clinical trial, balapiravir, a prodrug of a cytidine analog (R1479), failed to achieve efficacy (reducing viremia after treatment) in dengue patients, although the plasma trough concentration of R1479 remained above the 50% effective concentration (EC(50)). Here, we report experimental evidence to explain the discrepancy between the in vitro and in vivo results and its implication for drug development. R1479 lost its potency by 125-fold when balapiravir was used to treat primary human peripheral blood mononuclear cells (PBMCs; one of the major cells targeted for viral replication) that were preinfected with dengue virus. The elevated EC(50) was greater than the plasma trough concentration of R1479 observed in dengue patients treated with balapiravir and could possibly explain the efficacy failure. Mechanistically, dengue virus infection triggered PBMCs to generate cytokines, which decreased their efficiency of conversion of R1479 to its triphosphate form (the active antiviral ingredient), resulting in decreased antiviral potency. In contrast to the cytidine-based compound R1479, the potency of an adenosine-based inhibitor of dengue virus (NITD008) was much less affected. Taken together, our results demonstrate that viral infection in patients before treatment could significantly affect the conversion of the prodrug to its active form; such an effect should be calculated when estimating the dose efficacious for humans.

  15. Understanding Oxidative Stress in Aedes during Chikungunya and Dengue Virus Infections Using Integromics Analysis

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    Jatin Shrinet

    2018-06-01

    Full Text Available Arboviral infection causes dysregulation of cascade of events involving numerous biomolecules affecting fitness of mosquito to combat virus. In response of the viral infection mosquito’s defense mechanism get initiated. Oxidative stress is among the first host responses triggered by the vector. Significant number of information is available showing changes in the transcripts and/or proteins upon Chikungunya virus and Dengue virus mono-infections and as co-infections. In the present study, we collected different -omics data available in the public database along with the data generated in our laboratory related to mono-infections or co-infections of these viruses. We analyzed the data and classified them into their respective pathways to study the role of oxidative stress in combating arboviral infection in Aedes mosquito. The analysis revealed that the oxidative stress related pathways functions in harmonized manner.

  16. Modulation of inflammation and pathology during dengue virus infection by p38 MAPK inhibitor SB203580.

    Science.gov (United States)

    Fu, Yilong; Yip, Andy; Seah, Peck Gee; Blasco, Francesca; Shi, Pei-Yong; Hervé, Maxime

    2014-10-01

    Dengue virus (DENV) infection could lead to dengue fever (DF), dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). The disease outcome is controlled by both viral and host factors. Inflammation mediators from DENV-infected cells could contribute to increased vascular permeability, leading to severe DHF/DSS. Therefore, suppression of inflammation could be a potential therapeutic approach for treatment of dengue patients. In this context, p38 MAPK (mitogen-activated protein kinase) is a key enzyme that modulates the initiation of stress and inflammatory responses. Here we show that SB203580, a p38 MAPK inhibitor, suppressed the over production of DENV-induced pro-inflammatory mediators such as TNF-α, IL-8, and RANTES from human PBMCs, monocytic THP-1, and granulocyte KU812 cell lines. Oral administration of SB203580 in DENV-infected AG129 mice prevented hematocrit rise and lymphopenia, limited the development of inflammation and pathology (including intestine leakage), and significantly improved survival. These results, for the first time, have provided experimental evidence to imply that a short term inhibition of p38 MAPK may be beneficial to reduce disease symptoms in dengue patients. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Transcytosis Involvement in Transport System and Endothelial Permeability of Vascular Leakage during Dengue Virus Infection

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    Chanettee Chanthick

    2018-02-01

    Full Text Available The major role of endothelial cells is to maintain homeostasis of vascular permeability and to preserve the integrity of vascular vessels to prevent fluid leakage. Properly functioning endothelial cells promote physiological balance and stability for blood circulation and fluid components. A monolayer of endothelial cells has the ability to regulate paracellular and transcellular pathways for transport proteins, solutes, and fluid. In addition to the paracellular pathway, the transcellular pathway is another route of endothelial permeability that mediates vascular permeability under physiologic conditions. The transcellular pathway was found to be associated with an assortment of disease pathogeneses. The clinical manifestation of severe dengue infection in humans is vascular leakage and hemorrhagic diatheses. This review explores and describes the transcellular pathway, which is an alternate route of vascular permeability during dengue infection that corresponds with the pathologic finding of intact tight junction. This pathway may be the route of albumin transport that causes endothelial dysfunction during dengue virus infection.

  18. Identification of natural antimicrobial agents to treat dengue infection: In vitro analysis of latarcin peptide activity against dengue virus.

    Science.gov (United States)

    Rothan, Hussin A; Bahrani, Hirbod; Rahman, Noorsaadah Abd; Yusof, Rohana

    2014-05-31

    Although there have been considerable advances in the study of dengue virus, no vaccines or anti-dengue drugs are currently available for humans. Therefore, new approaches are necessary for the development of potent anti-dengue drugs. Natural antimicrobial peptides (AMPs) with potent antiviral activities are potential hits-to-leads for antiviral drug discovery. We performed this study to identify and characterise the inhibitory potential of the latarcin peptide (Ltc 1, SMWSGMWRRKLKKLRNALKKKLKGE) against dengue virus replication in infected cells. The Ltc 1 peptide showed a significantly inhibitory effect against the dengue protease NS2B-NS3pro at 37°C, a physiological human temperature, (IC50, 12.68 ± 3.2 μM), and greater inhibitory effect was observed at 40°C, a temperature similar to a high fever (IC50, 6.58 ± 4.1 μM). A greater reduction in viral load (p.f.u./ml) was observed at simultaneous (0.7 ± 0.3 vs. 7.2 ± 0.5 control) and post-treatment (1.8 ± 0.7 vs. 6.8 ± 0.6 control) compared to the pre-treatment (4.5 ± 0.6 vs. 6.9 ± 0.5 control). Treatment with the Ltc 1 peptide reduced the viral RNA in a dose-dependent manner with EC50 values of 8.3 ± 1.2, 7.6 ± 2.7 and 6.8 ± 2.5 μM at 24, 48 and 72 h, respectively. The Ltc 1 peptide exhibited significant inhibitory effects against dengue NS2B-NS3pro and virus replication in the infected cells. Therefore, further investigation is necessary to develop the Ltc 1 peptide as a new anti-dengue therapeutic.

  19. Dengue virus requires the CC-chemokine receptor CCR5 for replication and infection development.

    Science.gov (United States)

    Marques, Rafael E; Guabiraba, Rodrigo; Del Sarto, Juliana L; Rocha, Rebeca F; Queiroz, Ana Luiza; Cisalpino, Daniel; Marques, Pedro E; Pacca, Carolina C; Fagundes, Caio T; Menezes, Gustavo B; Nogueira, Maurício L; Souza, Danielle G; Teixeira, Mauro M

    2015-08-01

    Dengue is a mosquito-borne disease that affects millions of people worldwide yearly. Currently, there is no vaccine or specific treatment available. Further investigation on dengue pathogenesis is required to better understand the disease and to identify potential therapeutic targets. The chemokine system has been implicated in dengue pathogenesis, although the specific role of chemokines and their receptors remains elusive. Here we describe the role of the CC-chemokine receptor CCR5 in Dengue virus (DENV-2) infection. In vitro experiments showed that CCR5 is a host factor required for DENV-2 replication in human and mouse macrophages. DENV-2 infection induces the expression of CCR5 ligands. Incubation with an antagonist prevents CCR5 activation and reduces DENV-2 positive-stranded (+) RNA inside macrophages. Using an immunocompetent mouse model of DENV-2 infection we found that CCR5(-/-) mice were resistant to lethal infection, presenting at least 100-fold reduction of viral load in target organs and significant reduction in disease severity. This phenotype was reproduced in wild-type mice treated with CCR5-blocking compounds. Therefore, CCR5 is a host factor required for DENV-2 replication and disease development. Targeting CCR5 might represent a therapeutic strategy for dengue fever. These data bring new insights on the association between viral infections and the chemokine receptor CCR5. © 2015 John Wiley & Sons Ltd.

  20. Characterization of Dengue Virus Infections Among Febrile Children Clinically Diagnosed With a Non-Dengue Illness, Managua, Nicaragua.

    Science.gov (United States)

    Waggoner, Jesse J; Gresh, Lionel; Mohamed-Hadley, Alisha; Balmaseda, Angel; Soda, K James; Abeynayake, Janaki; Sahoo, Malaya K; Liu, Yuanyuan; Kuan, Guillermina; Harris, Eva; Pinsky, Benjamin A

    2017-06-15

    We sought to characterize dengue virus (DENV) infections among febrile children enrolled in a pediatric cohort study who were clinically diagnosed with a non-dengue illness ("C cases"). DENV infections were detected and viral load quantitated by real-time reverse transcription-polymerase chain reaction in C cases presenting between January 2007 and January 2013. One hundred forty-one of 2892 C cases (4.88%) tested positive for DENV. Of all febrile cases in the study, DENV-positive C cases accounted for an estimated 52.0% of patients with DENV viremia at presentation. Compared with previously detected, symptomatic dengue cases, DENV-positive C cases were significantly less likely to develop long-lasting humoral immune responses to DENV, as measured in healthy annual serum samples (79.7% vs 47.8%; P dengue. These findings have important implications for DENV transmission modeling, immunology, and epidemiologic surveillance. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  1. Clinical and laboratory profile of Zika virus infection in dengue suspected patients: A case series.

    Science.gov (United States)

    Fernanda Estofolete, Cássia; Terzian, Ana Carolina Bernardes; Parreira, Ricardo; Esteves, Aida; Hardman, Lucas; Greque, Gilmar Valdir; Rahal, Paula; Nogueira, Maurício Lacerda

    2016-08-01

    The Zika virus (ZIKV) is an emerging arthropod-borne virus related to the dengue virus (DENV), and shows a similar clinical profile as other arboviral diseases, such as dengue and chikungunya virus (CHIKV). Historically, ZIKV has been associated with sporadic cases of human infection, but is now responsible for outbreaks worldwide. In Brazil, cases have been reported since 2015, with some cases causing severe disease. To identify clinical symptoms of Zika in patients in Dengue suspected patients. Description of a series of cases, wherein we analyzed 100 clinical samples collected from patients who exhibited acute febrile disease for ≤5days, from January to February 2016. In this study, we report 13 cases of ZIKV infection in adults presenting dengue-like symptoms in a DENV endemic area. All patients presented with fever, with myalgia being the second most frequently observed symptom. Two patients had rashes, but none of them had conjunctivitis. Other less frequent manifestations included headache, arthralgia, diarrhea, and nausea. The co-circulation of ZIKV and DENV is a serious public health concern, since it represents both a clinical and diagnostic challenge in endemic areas, as well as in the field of travel medicine. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. SERO-EPIDEMIOLOGY OF DENGUE VIRUS INFECTION IN CITIES OF INDONESIA

    Directory of Open Access Journals (Sweden)

    Soegeng Soegijanto

    2013-10-01

    Full Text Available Background: Dengue Virus Infektion is major public health problem in Indonesia. Aedesaegypti is widespread in both urban and rural areas, where multiple virus Serotype are circulating. On 2013 outbreak ofdengue virus infection occur in East Java. Therefore study seroepidemiology in Bangkalan and Lombok had been done. Aim:to find a mutated strain ofDengue Virus in 4 cities ofIndonesia. Method: On 2011 and 2012 seroepidemiology study had been done in Dr. Soetomo Surabaya and Soerya Sidoarjo Hospital; and on 2013 study had been done in Surabaya, Bangkalan and Lombok Hospital . Diagnosis ofDengue Virus Infection was based on Criteri WHO - 2009. Virus isolation in Surabaya, Sidoarjo, Bangkalan and Lombok had been done. Result:a total of349 isolate were obtained from dengue patients sera collected in Surabaya and Sidoarjo, 2011–2012 showed that Den V1 (182, Den V2 (20 Den V4 (1 were found in Surabaya on 2011 and Den V 1 (79 , Den V 2 (7 were found in Surabaya on 2012; Den V1 (40, Den V 2 (3 were found in Sidoarjo on 2011 and Den V 1 (17 were found in Sidoarjo on 2012; Virus isolation in Surabaya on 2013, January: 237 serum sample were collected, found Den V 1 (8, Den V 3 (2 and Den V 4 (5. And PCR stereotyping of isolated viruses in Madura found Den V 1 (1 and Den V 4 (23. In Lombok found Den V 4 (4.It is possible to shift predominant strain in Surabaya , Genotype or Serotype shift might increase the number ofdengue patients. Conclusion: there were shift predominant strain in Surabaya especially Den V 1. Therefore to continuous surveillance ofcirculating viruses is required to predict the risk ofDHF and DF

  3. Effects of cell culture and laboratory conditions on type 2 dengue virus infectivity.

    Science.gov (United States)

    Manning, J S; Collins, J K

    1979-01-01

    The stability of type 2 dengue virus to exposure to a variety of laboratory conditions was determined. Suckling mouse brain passage virus was adapted for growth in BHK-21 cells, and plaque assays were performed using a tragacanth gum overlay. A three- to fourfold increase in plaque size could be obtained if monolayers were subconfluent at time of inoculation. Incubation of virus for 24 h at 37 degrees C, pH 6.5, or in buffer containing 1 mM ethylenediaminetetraacetate considerably reduced virus infectivity as compared with virus incubated for the same period at 4 degrees C, pH 8.0, or in buffer with or without 1 mM CaCl2 and 1 mM MgCl2. Multiple freezing and thawing of virus tissue culture medium containing 10% fetal calf serum did not reduce virus infectivity. Images PMID:41848

  4. Comparative Evaluation of Permissiveness to Dengue Virus Serotype 2 Infection in Primary Rodent Macrophages

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    Jeanette Prada-Arismendy

    2012-01-01

    Full Text Available Infection with dengue virus presents a broad clinical spectrum, which can range from asymptomatic cases to severe cases that are characterised by haemorrhagic syndrome and/or shock. The reason for such variability remains unknown. This work evaluated the in vitro permissiveness of mouse, rat, hamster and guinea pig macrophages to infection by dengue virus 2 (DENV2. The results established that macrophages derived from the BALB/c mouse strain showed higher permissiveness to DENV2 infection than macrophages from other rodent species, although all rodent species studied had the C820T mutation in the oligoadenylate synthetase 1b gene, indicating no relationship to the different in vitro susceptibilities of mouse cells at this locus. Other molecular mechanisms related to flavivirus susceptibility remain to be explored.

  5. Longitudinal Analysis of Natural Killer Cells in Dengue Virus-Infected Patients in Comparison to Chikungunya and Chikungunya/Dengue Virus-Infected Patients.

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    Caroline Petitdemange

    2016-03-01

    Full Text Available Dengue virus (DENV is the most prominent arbovirus worldwide, causing major epidemics in South-East Asia, South America and Africa. In 2010, a major DENV-2 outbreak occurred in Gabon with cases of patients co-infected with chikungunya virus (CHIKV. Although the innate immune response is thought to be of primordial importance in the development and outcome of arbovirus-associated pathologies, our knowledge of the role of natural killer (NK cells during DENV-2 infection is in its infancy.We performed the first extensive comparative longitudinal characterization of NK cells in patients infected by DENV-2, CHIKV or both viruses. Hierarchical clustering and principal component analyses were performed to discriminate between CHIKV and DENV-2 infected patients.We observed that both activation and differentiation of NK cells are induced during the acute phase of infection by DENV-2 and CHIKV. Combinatorial analysis however, revealed that both arboviruses induced two different signatures of NK-cell responses, with CHIKV more associated with terminal differentiation, and DENV-2 with inhibitory KIRs. We show also that intracellular production of interferon-γ (IFN-γ by NK cells is strongly stimulated in acute DENV-2 infection, compared to CHIKV.Although specific differences were observed between CHIKV and DENV-2 infections, the significant remodeling of NK cell populations observed here suggests their potential roles in the control of both infections.

  6. Utility of humanized BLT mice for analysis of dengue virus infection and antiviral drug testing.

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    Frias-Staheli, Natalia; Dorner, Marcus; Marukian, Svetlana; Billerbeck, Eva; Labitt, Rachael N; Rice, Charles M; Ploss, Alexander

    2014-02-01

    Dengue virus (DENV) is the cause of a potentially life-threatening disease that affects millions of people worldwide. The lack of a small animal model that mimics the symptoms of DENV infection in humans has slowed the understanding of viral pathogenesis and the development of therapies and vaccines. Here, we investigated the use of humanized "bone marrow liver thymus" (BLT) mice as a model for immunological studies and assayed their applicability for preclinical testing of antiviral compounds. Human immune system (HIS) BLT-NOD/SCID mice were inoculated intravenously with a low-passage, clinical isolate of DENV-2, and this resulted in sustained viremia and infection of leukocytes in lymphoid and nonlymphoid organs. In addition, DENV infection increased serum cytokine levels and elicited DENV-2-neutralizing human IgM antibodies. Following restimulation with DENV-infected dendritic cells, in vivo-primed T cells became activated and acquired effector function. An adenosine nucleoside inhibitor of DENV decreased the circulating viral RNA when administered simultaneously or 2 days postinfection, simulating a potential treatment protocol for DENV infection in humans. In summary, we demonstrate that BLT mice are susceptible to infection with clinical DENV isolates, mount virus-specific adaptive immune responses, and respond to antiviral drug treatment. Although additional refinements to the model are required, BLT mice are a suitable platform to study aspects of DENV infection and pathogenesis and for preclinical testing of drug and vaccine candidates. IMPORTANCE Infection with dengue virus remains a major medical problem. Progress in our understanding of the disease and development of therapeutics has been hampered by the scarcity of small animal models. Here, we show that humanized mice, i.e., animals engrafted with components of a human immune system, that were infected with a patient-derived dengue virus strain developed clinical symptoms of the disease and mounted

  7. Dengue virus infection among long-term travelers from the Netherlands: A prospective study, 2008-2011

    NARCIS (Netherlands)

    Overbosch, Femke W.; Schinkel, Janke; Stolte, Ineke G.; Prins, Maria; Sonder, Gerard J. B.

    2018-01-01

    Dengue is increasing rapidly in endemic regions. Data on incidence among travelers to these areas are limited. Five prospective studies have been performed thus far, mainly among short-term travelers. To obtain the attack and incidence rate (AR, IR) of dengue virus (DENV) infection among long-term

  8. AWARENESS OF USING RINGER LACTAT SOLUTION IN DENGUE VIRUS INFECTION CASES COULD INDUCE SEVERITY

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    Soegeng Soegijanto

    2013-10-01

    Full Text Available Background:In 2012, serotype ofDengue Virus had changed from Den-2 and Den-3 to Den-1. In 5–10 years ago, serotype ofDen-1 case showed a mild clinical manifestation; but now as a primary case it can also show severe clinical manifestation. One findicator is an increasing liver enzyme, AST and ALT, with level more than 100–200 U/L. Aim: To getting a better solutions for this problem. Method: Obsevasional Study had been done in medical faculty ofAirlangga University (Dr. Soetomo and Soerya hospital Surabaya on Mei–August 2012. There were 10 cases ofdengue virus infection were studied, 5 cases got Ringer Acetate solution (Group A and 5 cases got Ringer Lactate solution (Group B. The diagnosis was based on criteria WHO 2009. Result: Five cases ofDengue Virus Infection had showed a liver damage soon after using Ringer Lactate solution; AST and ALT were increasing more than 100–200 U/L; but the other 5 cases showed better condition. It might be due to use Ringer Acetate that did not have effect for inducing liver damage. By managing carefully, all of the cases had shown full recovery and healthy condition when being discharged. Conclusion: Using Ringer Acetate as fluid therapy in Dengue Virus Infection is better to prevent liver damage than using Ringer Lactate.

  9. Dengue virus infection-enhancing antibody activities against Indonesian strains in inhabitants of central Thailand.

    Science.gov (United States)

    Yamanaka, Atsushi; Oddgun, Duangjai; Chantawat, Nantarat; Okabayashi, Tamaki; Ramasoota, Pongrama; Churrotin, Siti; Kotaki, Tomohiro; Kameoka, Masanori; Soegijanto, Soegeng; Konishi, Eiji

    2016-04-01

    Dengue virus (DENV) infection-enhancing antibodies are a hypothetic factor to increase the dengue disease severity. In this study, we investigated the enhancing antibodies against Indonesian strains of DENV-1-4 in 50 healthy inhabitants of central Thailand (Bangkok and Uthai Thani). Indonesia and Thailand have seen the highest dengue incidence in Southeast Asia. The infection history of each subject was estimated by comparing his/her neutralizing antibody titers against prototype DENV-1-4 strains. To resolve the difficulty in obtaining foreign live viruses for use as assay antigens, we used a recombinant system to prepare single-round infectious dengue viral particles based on viral sequence information. Irrespective of the previously infecting serotype(s), most serum samples showed significantly higher enhancement titers against Indonesian DENV-2 strains than against Thai DENV-2 strains, whereas the opposite effect was observed for the DENV-3 strains. Equivalent enhancing activities were observed against both DENV-1 and DENV-4. These results suggest that the genotype has an impact on enhancing antibody activities against DENV-2 and DENV-3, because the predominant circulating genotypes of each serotype differ between Indonesia and Thailand. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  10. Human Immune Response to Dengue Infections

    Science.gov (United States)

    1991-06-30

    had been immunized with yellow fever vaccine and later became infected with dengue 3 virus, responded best to dengue 3 antigen but also responded to...effective dengue virus subunit vaccines . We found evidence of marked T cell activation in patients with DHF. T cell activation in patients with DF was similar...Treatment and Control of Dengue Hemorrhagic Fever. World Health Organization, Geneva, Switzerland 7. Sabin AB (1952) Research on dengue during World

  11. Response to Dengue virus infections altered by cytokine-like substances from mosquito cell cultures

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    Laosutthipong Chaowanee

    2010-11-01

    Full Text Available Abstract Background With both shrimp and commercial insects such as honey bees, it is known that stable, persistent viral infections characterized by absence of disease can sometimes shift to overt disease states as a result of various stress triggers and that this can result in serious economic losses. The main research interest of our group is to understand the dynamics of stable viral infections in shrimp and how they can be destabilized by stress. Since there are no continuous cell lines for crustaceans, we have used a C6/36 mosquito cell line infected with Dengue virus to test hypotheses regarding these interactions. As a result, we accidentally discovered two new cytokine-like substances in 5 kDa extracts from supernatant solutions of acutely and persistently infected mosquito cells. Results Naïve C6/36 cells were exposed for 48 h to 5 kDa membrane filtrates prepared from the supernatant medium of stable C6/36 mosquito cell cultures persistently-infected with Dengue virus. Subsequent challenge of naïve cells with a virulent stock of Dengue virus 2 (DEN-2 and analysis by confocal immunofluorescence microscopy using anti-DEN-2 antibody revealed a dramatic reduction in the percentage of DEN-2 infected cells when compared to control cells. Similar filtrates prepared from C6/36 cells with acute DEN-2 infections were used to treat stable C6/36 mosquito cell cultures persistently-infected with Dengue virus. Confocal immunofluorescence microscopy revealed destabilization in the form of an apoptosis-like response. Proteinase K treatment removed the cell-altering activities indicating that they were caused by small polypeptides similar to those previously reported from insects. Conclusions This is the first report of cytokine-like substances that can alter the responses of mosquito cells to Dengue virus. This simple model system allows detailed molecular studies on insect cytokine production and on cytokine activity in a standard insect cell line.

  12. Zika virus infection-the next wave after dengue?

    Science.gov (United States)

    Wong, Samson Sai-Yin; Poon, Rosana Wing-Shan; Wong, Sally Cheuk-Ying

    2016-04-01

    Zika virus was initially discovered in east Africa about 70 years ago and remained a neglected arboviral disease in Africa and Southeast Asia. The virus first came into the limelight in 2007 when it caused an outbreak in Micronesia. In the ensuing decade, it spread widely in other Pacific islands, after which its incursion into Brazil in 2015 led to a widespread epidemic in Latin America. In most infected patients the disease is relatively benign. Serious complications include Guillain-Barré syndrome and congenital infection which may lead to microcephaly and maculopathy. Aedes mosquitoes are the main vectors, in particular, Ae. aegypti. Ae. albopictus is another potential vector. Since the competent mosquito vectors are highly prevalent in most tropical and subtropical countries, introduction of the virus to these areas could readily result in endemic transmission of the disease. The priorities of control include reinforcing education of travellers to and residents of endemic areas, preventing further local transmission by vectors, and an integrated vector management programme. The container habitats of Ae. aegypti and Ae. albopictus means engagement of the community and citizens is of utmost importance to the success of vector control. Copyright © 2016. Published by Elsevier B.V.

  13. Microparticles provide a novel biomarker to predict severe clinical outcomes of dengue virus infection.

    Science.gov (United States)

    Punyadee, Nuntaya; Mairiang, Dumrong; Thiemmeca, Somchai; Komoltri, Chulaluk; Pan-Ngum, Wirichada; Chomanee, Nusara; Charngkaew, Komgrid; Tangthawornchaikul, Nattaya; Limpitikul, Wannee; Vasanawathana, Sirijitt; Malasit, Prida; Avirutnan, Panisadee

    2015-02-01

    Shedding of microparticles (MPs) is a consequence of apoptotic cell death and cellular activation. Low levels of circulating MPs in blood help maintain homeostasis, whereas increased MP generation is linked to many pathological conditions. Herein, we investigated the role of MPs in dengue virus (DENV) infection. Infection of various susceptible cells by DENV led to apoptotic death and MP release. These MPs harbored a viral envelope protein and a nonstructural protein 1 (NS1) on their surfaces. Ex vivo analysis of clinical specimens from patients with infections of different degrees of severity at multiple time points revealed that MPs generated from erythrocytes and platelets are two major MP populations in the circulation of DENV-infected patients. Elevated levels of red blood cell-derived MPs (RMPs) directly correlated with DENV disease severity, whereas a significant decrease in platelet-derived MPs was associated with a bleeding tendency. Removal by mononuclear cells of complement-opsonized NS1-anti-NS1 immune complexes bound to erythrocytes via complement receptor type 1 triggered MP shedding in vitro, a process that could explain the increased levels of RMPs in severe dengue. These findings point to the multiple roles of MPs in dengue pathogenesis. They offer a potential novel biomarker candidate capable of differentiating dengue fever from the more serious dengue hemorrhagic fever. Dengue is the most important mosquito-transmitted viral disease in the world. No vaccines or specific treatments are available. Rapid diagnosis and immediate treatment are the keys to achieve a positive outcome. Dengue virus (DENV) infection, like some other medical conditions, changes the level and composition of microparticles (MPs), tiny bag-like structures which are normally present at low levels in the blood of healthy individuals. This study investigated how MPs in culture and patients' blood are changed in response to DENV infection. Infection of cells led to programmed

  14. A non mouse-adapted dengue virus strain as a new model of severe dengue infection in AG129 mice.

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    Grace K Tan

    Full Text Available The spread of dengue (DEN worldwide combined with an increased severity of the DEN-associated clinical outcomes have made this mosquito-borne virus of great global public health importance. Progress in understanding DEN pathogenesis and in developing effective treatments has been hampered by the lack of a suitable small animal model. Most of the DEN clinical isolates and cell culture-passaged DEN virus strains reported so far require either host adaptation, inoculation with a high dose and/or intravenous administration to elicit a virulent phenotype in mice which results, at best, in a productive infection with no, few, or irrelevant disease manifestations, and with mice dying within few days at the peak of viremia. Here we describe a non-mouse-adapted DEN2 virus strain (D2Y98P that is highly infectious in AG129 mice (lacking interferon-alpha/beta and -gamma receptors upon intraperitoneal administration. Infection with a high dose of D2Y98P induced cytokine storm, massive organ damage, and severe vascular leakage, leading to haemorrhage and rapid death of the animals at the peak of viremia. In contrast, very interestingly and uniquely, infection with a low dose of D2Y98P led to asymptomatic viral dissemination and replication in relevant organs, followed by non-paralytic death of the animals few days after virus clearance, similar to the disease kinetic in humans. Spleen damage, liver dysfunction and increased vascular permeability, but no haemorrhage, were observed in moribund animals, suggesting intact vascular integrity, a cardinal feature in DEN shock syndrome. Infection with D2Y98P thus offers the opportunity to further decipher some of the aspects of dengue pathogenesis and provides a new platform for drug and vaccine testing.

  15. Simultaneous outbreaks of dengue, chikungunya and Zika virus infections: diagnosis challenge in a returning traveller with nonspecific febrile illness

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    E. Moulin

    2016-05-01

    Full Text Available Zika virus is an emerging flavivirus that is following the path of dengue and chikungunya. The three Aedes-borne viruses cause simultaneous outbreaks with similar clinical manifestations which represents a diagnostic challenge in ill returning travellers. We report the first Zika virus infection case imported to Switzerland and present a diagnostic algorithm.

  16. Flavone Enhances Dengue Virus Type-2 (NGC Strain Infectivity and Replication in Vero Cells

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    Keivan Zandi

    2012-02-01

    Full Text Available This study investigates the effects of 2-phenyl-1-benzopyran-4-one (flavone on DENV-2 infectivity in Vero cells. Virus adsorption and attachment and intracellular virus replication were investigated using a foci forming unit assay (FFUA and quantitative RT-PCR, respectively. Addition of flavone (100 μg/mL significantly increased the number of DENV-2 foci by 35.66% ± 1.52 and 49.66% ± 2.51 when added during and after virus adsorption to the Vero cells, respectively. The average foci size after 4 days of infection increased by 33% ± 2.11 and 89% ± 2.13. The DENV-2 specific RNA copy number in the flavone-treated infected cells increased by 6.41- and 23.1-fold when compared to the mock-treated infected cells. Flavone (100 μg/mL did not promote or inhibit Vero cell proliferation. The CC50 value of flavone against Vero cells was 446 µg/mL. These results suggest that flavone might enhance dengue virus replication by acting antagonistically towards flavonoids known to inhibit dengue virus replication.

  17. Losartan and enalapril decrease viral absorption and interleukin 1 beta production by macrophages in an experimental dengue virus infection.

    Science.gov (United States)

    Hernández-Fonseca, Juan Pablo; Durán, Anyelo; Valero, Nereida; Mosquera, Jesús

    2015-11-01

    The role of angiotensin II (Ang II) in dengue virus infection remains unknown. The aim of this study was to determine the effect of losartan, an antagonist of the angiotensin II type 1 receptor (AT1 receptor), and enalapril, an inhibitor of angiotensin I-converting enzyme (ACE), on viral antigen expression and IL-1β production in peritoneal macrophages infected with dengue virus type 2. Mice treated with losartan or enalapril and untreated controls were infected intraperitoneally with the virus, and macrophages were analyzed. Infection resulted in increased IL-1β production and a high percentage of cells expressing viral antigen, and this was decreased by treatment with anti-Ang II drugs, suggesting a role for Ang II in dengue virus infection.

  18. Dengue virus serotype 2 infection alters midgut and carcass gene expression in the Asian tiger mosquito, Aedes albopictus.

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    Hitoshi Tsujimoto

    Full Text Available The Asian tiger mosquito, Aedes albopictus is currently an important vector for dengue, chikungunya and Zika virus, and its role in transmission of arthropod-borne viruses (arboviruses may increase in the future due to its ability to colonize temperate regions. In contrast to Aedes aegypti, the dominant vector of dengue, chikungunya and Zika virus, genetic responses of Ae. albopictus upon infection with an arbovirus are not well characterized. Here we present a study of the changes in transcript expression in Ae. albopictus exposed to dengue virus serotype 2 via feeding on an artificial bloodmeal.We isolated midguts and midgut-free carcasses of Ae. albopictus fed on bloodmeals containing dengue virus as well as controls fed on virus-free control meals at day 1 and day 5 post-feeding. We confirmed infection of midguts from mosquitoes sampled on day 5 post-feeding via RT-PCR. RNAseq analysis revealed dynamic modulation of the expression of several putative immunity and dengue virus-responsive genes, some of whose expression was verified by qRT-PCR. For example, a serine protease gene was up-regulated in the midgut at 1 day post infection, which may potentially enhance mosquito susceptibility to dengue infection, while 14 leucine-rich repeat genes, previously shown to be involved in mosquito antiviral defenses, were down-regulated in the carcass at 5 days post infection. The number of significantly modulated genes decreased over time in midguts and increased in carcasses.Dengue virus exposure results in the modulation of genes in a time- and site-specific manner. Previous literature on the interaction between mosquitoes and mosquito-borne pathogens suggests that most of the changes that occurred in Ae. albopictus exposed to DENV would favor virus infection. Many genes identified in this study warrant further characterization to understand their role in viral manipulation of and antiviral response of Ae. albopictus.

  19. An in vitro model for dengue virus infection that exhibits human monocyte infection, multiple cytokine production and dexamethasone immunomodulation

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    Sônia Regina Nogueira Ignácio Reis

    2007-12-01

    Full Text Available An important cytokine role in dengue fever pathogenesis has been described. These molecules can be associated with haemorrhagic manifestations, coagulation disorders, hypotension and shock, all symptoms implicated in vascular permeability and disease worsening conditions. Several immunological diseases have been treated by cytokine modulation and dexamethasone is utilized clinically to treat pathologies with inflammatory and autoimmune ethiologies. We established an in vitro model with human monocytes infected by dengue virus-2 for evaluating immunomodulatory and antiviral activities of potential pharmaceutical products. Flow cytometry analysis demonstrated significant dengue antigen detection in target cells two days after infection. TNF-alpha, IFN-alpha, IL-6 and IL-10 are produced by in vitro infected monocytes and are significantly detected in cell culture supernatants by multiplex microbead immunoassay. Dexamethasone action was tested for the first time for its modulation in dengue infection, presenting optimistic results in both decreasing cell infection rates and inhibiting TNF-alpha, IFN-alpha and IL-10 production. This model is proposed for novel drug trials yet to be applyed for dengue fever.

  20. Differential protein modulation in midguts of Aedes aegypti infected with chikungunya and dengue 2 viruses.

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    Stéphane Tchankouo-Nguetcheu

    Full Text Available BACKGROUND: Arthropod borne virus infections cause several emerging and resurgent infectious diseases. Among the diseases caused by arboviruses, dengue and chikungunya are responsible for a high rate of severe human diseases worldwide. The midgut of mosquitoes is the first barrier for pathogen transmission and is a target organ where arboviruses must replicate prior to infecting other organs. A proteomic approach was undertaken to characterize the key virus/vector interactions and host protein modifications that happen in the midgut for viral transmission to eventually take place. METHODOLOGY AND PRINCIPAL FINDINGS: Using a proteomics differential approach with two-Dimensional Differential in-Gel Electrophoresis (2D-DIGE, we defined the protein modulations in the midgut of Aedes aegypti that were triggered seven days after an oral infection (7 DPI with dengue 2 (DENV-2 and chikungunya (CHIKV viruses. Gel profile comparisons showed that the level of 18 proteins was modulated by DENV-2 only and 12 proteins were modulated by CHIKV only. Twenty proteins were regulated by both viruses in either similar or different ways. Both viruses caused an increase of proteins involved in the generation of reactive oxygen species, energy production, and carbohydrate and lipid metabolism. Midgut infection by DENV-2 and CHIKV triggered an antioxidant response. CHIKV infection produced an increase of proteins involved in detoxification. CONCLUSION/SIGNIFICANCE: Our study constitutes the first analysis of the protein response of Aedes aegypti's midgut infected with viruses belonging to different families. It shows that the differentially regulated proteins in response to viral infection include structural, redox, regulatory proteins, and enzymes for several metabolic pathways. Some of these proteins like antioxidant are probably involved in cell protection. On the other hand, we propose that the modulation of other proteins like transferrin, hsp60 and alpha

  1. Differential protein modulation in midguts of Aedes aegypti infected with chikungunya and dengue 2 viruses.

    Science.gov (United States)

    Tchankouo-Nguetcheu, Stéphane; Khun, Huot; Pincet, Laurence; Roux, Pascal; Bahut, Muriel; Huerre, Michel; Guette, Catherine; Choumet, Valérie

    2010-10-05

    Arthropod borne virus infections cause several emerging and resurgent infectious diseases. Among the diseases caused by arboviruses, dengue and chikungunya are responsible for a high rate of severe human diseases worldwide. The midgut of mosquitoes is the first barrier for pathogen transmission and is a target organ where arboviruses must replicate prior to infecting other organs. A proteomic approach was undertaken to characterize the key virus/vector interactions and host protein modifications that happen in the midgut for viral transmission to eventually take place. Using a proteomics differential approach with two-Dimensional Differential in-Gel Electrophoresis (2D-DIGE), we defined the protein modulations in the midgut of Aedes aegypti that were triggered seven days after an oral infection (7 DPI) with dengue 2 (DENV-2) and chikungunya (CHIKV) viruses. Gel profile comparisons showed that the level of 18 proteins was modulated by DENV-2 only and 12 proteins were modulated by CHIKV only. Twenty proteins were regulated by both viruses in either similar or different ways. Both viruses caused an increase of proteins involved in the generation of reactive oxygen species, energy production, and carbohydrate and lipid metabolism. Midgut infection by DENV-2 and CHIKV triggered an antioxidant response. CHIKV infection produced an increase of proteins involved in detoxification. Our study constitutes the first analysis of the protein response of Aedes aegypti's midgut infected with viruses belonging to different families. It shows that the differentially regulated proteins in response to viral infection include structural, redox, regulatory proteins, and enzymes for several metabolic pathways. Some of these proteins like antioxidant are probably involved in cell protection. On the other hand, we propose that the modulation of other proteins like transferrin, hsp60 and alpha glucosidase, may favour virus survival, replication and transmission, suggesting a subversion of

  2. Dengue viral infections

    OpenAIRE

    Malavige, G; Fernando, S; Fernando, D; Seneviratne, S

    2004-01-01

    Dengue viral infections are one of the most important mosquito borne diseases in the world. They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide. Ninety percent of DHF subjects are children less than 15 years of age. At present, dengue is endemic in 112 countries in the world. No vaccine is available for preventing...

  3. Secretion of Galectin-9 as a DAMP during Dengue Virus Infection in THP-1 Cells.

    Science.gov (United States)

    Dapat, Isolde C; Pascapurnama, Dyshelly Nurkartika; Iwasaki, Hiroko; Labayo, Hannah Karen; Chagan-Yasutan, Haorile; Egawa, Shinichi; Hattori, Toshio

    2017-07-28

    Damage-associated molecular patterns (DAMPs) are endogenous cellular molecules released to the extracellular environment in response to stress conditions such as virus infection. Galectins are β-galactoside-binding proteins that are widely expressed in cells and tissues of the immune system, are localized in the cell cytoplasm, and have roles in inflammatory responses and immune responses against infection. Elevated levels of galectin-9 (Gal-9) in natural human infections have been documented in numerous reports. To investigate the effect of dengue virus (DENV) infection on expression of endogenous Gal-9, monocytic THP-1 cells were infected with varying doses of DENV-3 (multiplicity of infection (MOI) 0.01, 0.03 and 0.1) and incubated at varying time points (Day 1, Day 2, Day 3). Results showed augmentation of Gal-9 levels in the supernatant, reduction of Gal-9 levels in the cells and decreased expression of LGALS9 mRNA, while DENV-3 mRNA copies for all three doses remained stable through time. Dengue virus induced the secretion of Gal-9 as a danger response; in turn, Gal-9 and other inflammatory factors, and stimulated effector responses may have limited further viral replication. The results in this pilot experiment add to the evidence of Gal-9 as a potential DAMP.

  4. Protective Role of Cross-Reactive CD8 T Cells Against Dengue Virus Infection

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    Annie Elong Ngono

    2016-11-01

    Full Text Available Infection with one of the four dengue virus serotypes (DENV1-4 presumably leads to lifelong immunity against the infecting serotype but not against heterotypic reinfection, resulting in a greater risk of developing Dengue Hemorrhagic Fever/Dengue Shock Syndrome (DHF/DSS during secondary infection. Both antibodies and T cell responses have been implicated in DHF/DSS pathogenesis. According to the T cell-based hypothesis termed “original antigenic sin,” secondary DENV infection is dominated by non-protective, cross-reactive T cells that elicit an aberrant immune response. The goal of our study was to compare the roles of serotype-specific and cross-reactive T cells in protection vs. pathogenesis during DENV infection in vivo. Specifically, we utilized IFN-α/βR−/− HLA*B0702 transgenic mice in the context of peptide vaccination with relevant human CD8 T cell epitopes. IFN-α/βR−/− HLA*B0702 transgenic mice were immunized with DENV serotype 2 (DENV2-specific epitopes or variants found in any of the other three serotypes (DENV1, DENV3 or DENV4, followed by challenge with DENV. Although cross-reactive T cell responses were lower than responses elicited by serotype-specific T cells, immunization with either serotype-specific or variant peptide epitopes enhanced viral clearance, demonstrating that both serotype-specific and cross-reactive T cells can contribute to protection in vivo against DENV infection.

  5. Identification of dengue viruses in naturally infected Aedes aegypti females captured with BioGents (BG-Sentinel traps in Manaus, Amazonas, Brazil

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    Regina Maria Pinto de Figueiredo

    2013-04-01

    Full Text Available Introduction In Manaus, the first autochthonous cases of dengue fever were registered in 1998. Since then, dengue cases were diagnosed by the isolation of viruses 1, 2, 3, and 4. Methods One hundred eighty-seven mosquitoes were collected with BioGents (BG-Sentinel traps in 15 urban residential areas in the Northern Zone of Manaus and processed by molecular tests. Results Infections with dengue viruses 1, 2, 3, and 4 and a case of co-infection with dengue viruses 2 and 3 were identified. Conclusions These findings corroborate the detection of dengue in clinical samples and reinforce the need for epidemiological surveillance by the Health authorities.

  6. Increased Levels of Txa₂ Induced by Dengue Virus Infection in IgM Positive Individuals Is Related to the Mild Symptoms of Dengue.

    Science.gov (United States)

    Oliveira, Eneida S; Colombarolli, Stella G; Nascimento, Camila S; Batista, Izabella C A; Ferreira, Jorge G G; Alvarenga, Daniele L R; de Sousa, Laís O B; Assis, Rafael R; Rocha, Marcele N; Alves, Érica A R; Calzavara-Silva, Carlos E

    2018-02-28

    The inflammatory process plays a major role in the prognosis of dengue. In this context, the eicosanoids may have considerable influence on the regulation of the Dengue virus -induced inflammatory process. To quantify the molecules involved in the cyclooxygenase and lipoxygenase pathways during Dengue virus infection, plasma levels of thromboxane A2, prostaglandin E2 and leukotriene B4; mRNA levels of thromboxane A2 synthase, prostaglandin E2 synthase, leukotriene A4 hydrolase, cyclooxygenase-2 and 5-lipoxygenase; and the levels of lipid bodies in peripheral blood leukocytes collected from IgM-positive and IgM-negative volunteers with mild dengue, and non-infected volunteers, were evaluated. Dengue virus infection increases the levels of thromboxane A2 in IgM-positive individuals as well as the amount of lipid bodies in monocytes in IgM-negative individuals. We suggest that increased levels of thromboxane A2 in IgM-positive individuals plays a protective role against the development of severe symptoms of dengue, such as vascular leakage.

  7. Increased Levels of Txa2 Induced by Dengue Virus Infection in IgM Positive Individuals Is Related to the Mild Symptoms of Dengue

    Science.gov (United States)

    Oliveira, Eneida S.; Colombarolli, Stella G.; Nascimento, Camila S.; Batista, Izabella C. A.; Ferreira, Jorge G. G.; Alvarenga, Daniele L. R.; de Sousa, Laís O. B.; Assis, Rafael R.; Rocha, Marcele N.; Alves, Érica A. R.; Calzavara-Silva, Carlos E.

    2018-01-01

    The inflammatory process plays a major role in the prognosis of dengue. In this context, the eicosanoids may have considerable influence on the regulation of the Dengue virus-induced inflammatory process. To quantify the molecules involved in the cyclooxygenase and lipoxygenase pathways during Dengue virus infection, plasma levels of thromboxane A2, prostaglandin E2 and leukotriene B4; mRNA levels of thromboxane A2 synthase, prostaglandin E2 synthase, leukotriene A4 hydrolase, cyclooxygenase-2 and 5-lipoxygenase; and the levels of lipid bodies in peripheral blood leukocytes collected from IgM-positive and IgM-negative volunteers with mild dengue, and non-infected volunteers, were evaluated. Dengue virus infection increases the levels of thromboxane A2 in IgM-positive individuals as well as the amount of lipid bodies in monocytes in IgM-negative individuals. We suggest that increased levels of thromboxane A2 in IgM-positive individuals plays a protective role against the development of severe symptoms of dengue, such as vascular leakage. PMID:29495587

  8. Dengue virus type 2: replication and tropisms in orally infected Aedes aegypti mosquitoes.

    Science.gov (United States)

    Salazar, Ma Isabel; Richardson, Jason H; Sánchez-Vargas, Irma; Olson, Ken E; Beaty, Barry J

    2007-01-30

    To be transmitted by its mosquito vector, dengue virus (DENV) must infect midgut epithelial cells, replicate and disseminate into the hemocoel, and finally infect the salivary glands, which is essential for transmission. The extrinsic incubation period (EIP) is very relevant epidemiologically and is the time required from the ingestion of virus until it can be transmitted to the next vertebrate host. The EIP is conditioned by the kinetics and tropisms of virus replication in its vector. Here we document the virogenesis of DENV-2 in newly-colonized Aedes aegypti mosquitoes from Chetumal, Mexico in order to understand better the effect of vector-virus interactions on dengue transmission. After ingestion of DENV-2, midgut infections in Chetumal mosquitoes were characterized by a peak in virus titers between 7 and 10 days post-infection (dpi). The amount of viral antigen and viral titers in the midgut then declined, but viral RNA levels remained stable. The presence of DENV-2 antigen in the trachea was positively correlated with virus dissemination from the midgut. DENV-2 antigen was found in salivary gland tissue in more than a third of mosquitoes at 4 dpi. Unlike in the midgut, the amount of viral antigen (as well as the percent of infected salivary glands) increased with time. DENV-2 antigen also accumulated and increased in neural tissue throughout the EIP. DENV-2 antigen was detected in multiple tissues of the vector, but unlike some other arboviruses, was not detected in muscle. Our results suggest that the EIP of DENV-2 in its vector may be shorter that the previously reported and that the tracheal system may facilitate DENV-2 dissemination from the midgut. Mosquito organs (e.g. midgut, neural tissue, and salivary glands) differed in their response to DENV-2 infection.

  9. Dengue virus type 2: replication and tropisms in orally infected Aedes aegypti mosquitoes

    Directory of Open Access Journals (Sweden)

    Olson Ken E

    2007-01-01

    Full Text Available Abstract Background To be transmitted by its mosquito vector, dengue virus (DENV must infect midgut epithelial cells, replicate and disseminate into the hemocoel, and finally infect the salivary glands, which is essential for transmission. The extrinsic incubation period (EIP is very relevant epidemiologically and is the time required from the ingestion of virus until it can be transmitted to the next vertebrate host. The EIP is conditioned by the kinetics and tropisms of virus replication in its vector. Here we document the virogenesis of DENV-2 in newly-colonized Aedes aegypti mosquitoes from Chetumal, Mexico in order to understand better the effect of vector-virus interactions on dengue transmission. Results After ingestion of DENV-2, midgut infections in Chetumal mosquitoes were characterized by a peak in virus titers between 7 and 10 days post-infection (dpi. The amount of viral antigen and viral titers in the midgut then declined, but viral RNA levels remained stable. The presence of DENV-2 antigen in the trachea was positively correlated with virus dissemination from the midgut. DENV-2 antigen was found in salivary gland tissue in more than a third of mosquitoes at 4 dpi. Unlike in the midgut, the amount of viral antigen (as well as the percent of infected salivary glands increased with time. DENV-2 antigen also accumulated and increased in neural tissue throughout the EIP. DENV-2 antigen was detected in multiple tissues of the vector, but unlike some other arboviruses, was not detected in muscle. Conclusion Our results suggest that the EIP of DENV-2 in its vector may be shorter that the previously reported and that the tracheal system may facilitate DENV-2 dissemination from the midgut. Mosquito organs (e.g. midgut, neural tissue, and salivary glands differed in their response to DENV-2 infection.

  10. Survey of malaria and anti-dengue virus IgG among febrile HIV-infected patients attending a tertiary hospital in Abuja, Nigeria.

    Science.gov (United States)

    Mustapha, Jelili Olaide; Emeribe, Anthony Uchenna; Nasir, Idris Abdullahi

    2017-01-01

    Dengue and malaria are infections, of great public health concern, especially in sub-Saharan Africa where the burden of HIV infection is high. This study was conducted to determine the seroprevalence of dengue virus IgG antibodies and dengue/malaria coinfection among febrile HIV-infected patients attending the University of Abuja Teaching Hospital, Gwagwalada, Abuja. In this cross-sectional study, blood samples from 178 consenting HIV-infected patients receiving antiretroviral therapy were collected and tested for plasmodiasis and anti-Dengue virus IgG using malaria microscopy and ELISA, respectively. Interviewer-based questionnaires were used to assess subjects' sociodemographic variables and dengue risk factors. Of the 178 screened participants, 44.4% were seropositive for dengue virus IgG antibody, whereas 29.2% were positive for Plasmodium falciparum. About 44.2% were positive for both dengue virus and P. falciparum . There was a statistical association between anti-dengue IgG and occupation ( p =0.03) but not with age, residential area, educational level and patients' gender ( p >0.05). Seroprevalence of anti-dengue specific IgG was relatively higher in participants who adopted protective measures. There was a statistical association between seroprevalence of anti-dengue IgG and adoption of preventive measures ( p <0.05). The high prevalence of malaria and dengue virus IgG indicates the need to strengthen vector control and dengue surveillance programs.

  11. Cytotoxic CD4 T Cells: Differentiation, Function, and Application to Dengue Virus Infection.

    Science.gov (United States)

    Tian, Yuan; Sette, Alessandro; Weiskopf, Daniela

    2016-01-01

    Dengue virus (DENV) has spread through most tropical and subtropical areas of the world and represents a serious public health problem. The control of DENV infection has not yet been fully successful due to lack of effective therapeutics or vaccines. Nevertheless, a better understanding of the immune responses against DENV infection may reveal new strategies for eliciting and improving antiviral immunity. T cells provide protective immunity against various viral infections by generating effector cells that cooperate to eliminate antigens and memory cells that can survive for long periods with enhanced abilities to control recurring pathogens. Following activation, CD8 T cells can migrate to sites of infection and kill infected cells, whereas CD4 T cells contribute to the elimination of pathogens by trafficking to infected tissues and providing help to innate immune responses, B cells, as well as CD8 T cells. However, it is now evident that CD4 T cells can also perform cytotoxic functions and induce the apoptosis of target cells. Importantly, accumulating studies demonstrate that cytotoxic CD4 T cells develop following DENV infections and may play a crucial role in protecting the host from severe dengue disease. We review our current understanding of the differentiation and function of cytotoxic CD4 T cells, with a focus on DENV infection, and discuss the potential of harnessing these cells for the prevention and treatment of DENV infection and disease.

  12. Molecular Responses of Human Retinal Cells to Infection with Dengue Virus.

    Science.gov (United States)

    Carr, Jillian M; Ashander, Liam M; Calvert, Julie K; Ma, Yuefang; Aloia, Amanda; Bracho, Gustavo G; Chee, Soon-Phaik; Appukuttan, Binoy; Smith, Justine R

    2017-01-01

    Recent clinical reports indicate that infection with dengue virus (DENV) commonly has ocular manifestations. The most serious threat to vision is dengue retinopathy, including retinal vasculopathy and macular edema. Mechanisms of retinopathy are unstudied, but observations in patients implicate retinal pigment epithelial cells and retinal endothelial cells. Human retinal cells were inoculated with DENV-2 and monitored for up to 72 hours. Epithelial and endothelial cells supported DENV replication and release, but epithelial cells alone demonstrated clear cytopathic effect, and infection was more productive in those cells. Infection induced type I interferon responses from both cells, but this was stronger in epithelial cells. Endothelial cells increased expression of adhesion molecules, with sustained overexpression of vascular adhesion molecule-1. Transcellular impedance decreased for epithelial monolayers, but not endothelial monolayers, coinciding with cytopathic effect. This reduction was accompanied by disorganization of intracellular filamentous-actin and decreased expression of junctional molecules, zonula occludens 1, and catenin- β 1. Changes in endothelial expression of adhesion molecules are consistent with the retinal vasculopathy seen in patients infected with DENV; decreases in epithelial junctional protein expression, paralleling loss of integrity of the epithelium, provide a molecular basis for DENV-associated macular edema. These molecular processes present potential therapeutic targets for vision-threatening dengue retinopathy.

  13. Molecular Responses of Human Retinal Cells to Infection with Dengue Virus

    Directory of Open Access Journals (Sweden)

    Jillian M. Carr

    2017-01-01

    Full Text Available Recent clinical reports indicate that infection with dengue virus (DENV commonly has ocular manifestations. The most serious threat to vision is dengue retinopathy, including retinal vasculopathy and macular edema. Mechanisms of retinopathy are unstudied, but observations in patients implicate retinal pigment epithelial cells and retinal endothelial cells. Human retinal cells were inoculated with DENV-2 and monitored for up to 72 hours. Epithelial and endothelial cells supported DENV replication and release, but epithelial cells alone demonstrated clear cytopathic effect, and infection was more productive in those cells. Infection induced type I interferon responses from both cells, but this was stronger in epithelial cells. Endothelial cells increased expression of adhesion molecules, with sustained overexpression of vascular adhesion molecule-1. Transcellular impedance decreased for epithelial monolayers, but not endothelial monolayers, coinciding with cytopathic effect. This reduction was accompanied by disorganization of intracellular filamentous-actin and decreased expression of junctional molecules, zonula occludens 1, and catenin-β1. Changes in endothelial expression of adhesion molecules are consistent with the retinal vasculopathy seen in patients infected with DENV; decreases in epithelial junctional protein expression, paralleling loss of integrity of the epithelium, provide a molecular basis for DENV-associated macular edema. These molecular processes present potential therapeutic targets for vision-threatening dengue retinopathy.

  14. Superior infectivity for mosquito vectors contributes to competitive displacement among strains of dengue virus

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    Schirtzinger Erin E

    2008-02-01

    Full Text Available Abstract Background Competitive displacement of a weakly virulent pathogen strain by a more virulent strain is one route to disease emergence. However the mechanisms by which pathogens compete for access to hosts are poorly understood. Among vector-borne pathogens, variation in the ability to infect vectors may effect displacement. The current study focused on competitive displacement in dengue virus serotype 3 (DENV3, a mosquito-borne pathogen of humans. In Sri Lanka in the 1980's, a native DENV3 strain associated with relatively mild dengue disease was displaced by an invasive DENV3 strain associated with the most severe disease manifestations, dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS, resulting in an outbreak of DHF/DSS. Here we tested the hypothesis that differences between the invasive and native strain in their infectivity for Aedes aegypti mosquitoes, the primary vector of DENV, contributed to the competitive success of the invasive strain Results To be transmitted by a mosquito, DENV must infect and replicate in the midgut, disseminate into the hemocoel, infect the salivary glands, and be released into the saliva. The ability of the native and invasive DENV3 strains to complete the first three steps of this process in Aedes aegypti mosquitoes was measured in vivo. The invasive strain infected a similar proportion of mosquitoes as the native strain but replicated to significantly higher titers in the midgut and disseminated with significantly greater efficiency than the native strain. In contrast, the native and invasive strain showed no significant difference in replication in cultured mosquito, monkey or human cells. Conclusion The invasive DENV3 strain infects and disseminates in Ae. aegypti more efficiently than the displaced native DENV3 strain, suggesting that the invasive strain is transmitted more efficiently. Replication in cultured cells did not adequately characterize the known phenotypic differences between

  15. Nine year trends of dengue virus infection in Mumbai, Western India

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    Jayanthi Shastri

    2017-01-01

    Methods and Results: During the nine year period of this study analysis, 6767 strongly suspected cases were tested by RT-PCR. 1685 (24.9% were Dengue PCR positive and confirmed as Dengue cases. Observations on the seasonality were based on the nine year's data as the intensity of sampling was at its maximum during monsoon season. Dengue typing was done on 100 positive samples after storage of Dengue RNA at – 80°C. Dengue serotypes were detected in 69 samples of which Dengue 2 was most predominant. 576 samples were processed for NS1 antigen and PCR simultaneously. 19/576 were positive (3.3 % for NS1 as well as by PCR . 23/576 samples were negative for NS1 antigen, but were positive by RT-PCR. The remaining 534 samples which were negative for NS1 antigen were also negative by Dengue RT-PCR. Conclusion: In this study we sought to standardize rapid, sensitive, and specific fluorogenic probe-based RT-PCR assay to screen and serotype a representative range of Dengue viruses that are found in and around Mumbai. Qualitative Dengue virus TaqMan assays could have tremendous utility for the epidemiological investigation of Dengue illness and especially for the study of the viremic response with candidate live-attenuated dengue virus vaccines.

  16. Incidence of dengue virus infections in febrile episodes in Ile-Ife ...

    African Journals Online (AJOL)

    While dengue infection is accompanied by little or no subclinical signs in many, about 1-2% may produce clinically severe Dengue Haemorrhagic Fever/Dengue Shock Syndrome. Early recognition, appropriate treatment and elimination of mosquito vectors will help control it. The study is aimed at determining the incidence ...

  17. Garlic Organosulfur Compounds Reduce Inflammation and Oxidative Stress during Dengue Virus Infection

    Science.gov (United States)

    Hall, Alex; Troupin, Andrea; Londono-Renteria, Berlin; Colpitts, Tonya M.

    2017-01-01

    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. PMID:28644404

  18. Garlic Organosulfur Compounds Reduce Inflammation and Oxidative Stress during Dengue Virus Infection.

    Science.gov (United States)

    Hall, Alex; Troupin, Andrea; Londono-Renteria, Berlin; Colpitts, Tonya M

    2017-06-23

    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.

  19. A Role for Human Skin Mast Cells in Dengue Virus Infection and Systemic Spread.

    Science.gov (United States)

    Troupin, Andrea; Shirley, Devon; Londono-Renteria, Berlin; Watson, Alan M; McHale, Cody; Hall, Alex; Hartstone-Rose, Adam; Klimstra, William B; Gomez, Gregorio; Colpitts, Tonya M

    2016-12-01

    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. Copyright © 2016 by The American Association of Immunologists, Inc.

  20. Occurrence of concurrent infections with multiple serotypes of dengue viruses during 2013–2015 in northern Kerala, India

    Directory of Open Access Journals (Sweden)

    Manchala Nageswar Reddy

    2017-03-01

    Full Text Available Background Dengue is a global human public health threat, causing severe morbidity and mortality. The occurrence of sequential infection by more than one serotype of dengue virus (DENV is a major contributing factor for the induction of Dengue Hemorrhagic Fever (DHF and Dengue Shock Syndrome (DSS, two major medical conditions caused by DENV infection. However, there is no specific drug or vaccine available against dengue infection. There are reports indicating the increased incidence of concurrent infection of dengue in several tropical and subtropical regions. Recently, increasing number of DHF and DSS cases were reported in India indicating potential enhancement of concurrent DENV infections. Therefore, accurate determination of the occurrence of DENV serotype co-infections needs to be conducted in various DENV prone parts of India. In this context, the present study was conducted to analyse the magnitude of concurrent infection in northern Kerala, a southwest state of India, during three consecutive years from 2013 to 2015. Methods A total of 120 serum samples were collected from the suspected dengue patients. The serum samples were diagnosed for the presence of dengue NS1 antigen followed by the isolation of dengue genome from NS1 positive samples. The isolated dengue genome was further subjected to RTPCR based molecular serotyping. The phylogenetic tree was constructed based on the sequence of PCR amplified products. Results Out of the total number of samples collected, 100 samples were positive for dengue specific antigen (NS1 and 26 of them contained the dengue genome. The RTPCR based molecular serotyping of the dengue genome revealed the presence of all four serotypes with different combinations. However, serotypes 1 and 3 were predominant combinations of concurrent infection. Interestingly, there were two samples with all four serotypes concurrently infected in 2013. Discussion All samples containing dengue genome showed the presence of

  1. Experimental in vitro and in vivo systems for studying the innate immune response during dengue virus infections.

    Science.gov (United States)

    Kitab, Bouchra; Kohara, Michinori; Tsukiyama-Kohara, Kyoko

    2018-03-08

    Dengue is the most prevalent arboviral disease in humans and leads to significant morbidity and socioeconomic burden in tropical and subtropical areas. Dengue is caused by infection with any of the four closely related serotypes of dengue virus (DENV1-4) and usually manifests as a mild febrile illness, but may develop into fatal dengue hemorrhagic fever and shock syndrome. There are no specific antiviral therapies against dengue because understanding of DENV biology is limited. A tetravalent chimeric dengue vaccine, Dengvaxia, has finally been licensed for use, but its efficacy was significantly lower against DENV-2 infections and in dengue-naïve individuals. The identification of mechanisms underlying the interactions between DENV and immune responses will help to determine efficient therapeutic and preventive options. It has been well established how the innate immune system responds to DENV infection and how DENV overcomes innate antiviral defenses, however further progress in this field remains hampered by the absence of appropriate experimental dengue models. Herein, we review the available in vitro and in vivo approaches to study the innate immune responses to DENV.

  2. Elevation of soluble VCAM-1 plasma levels in children with acute dengue virus infection of varying severity.

    NARCIS (Netherlands)

    Koraka, P.; Murgue, B.; Deparis, X.; Gorp, E. van; Setiati, T.E.; Osterhaus, A.D.; Groen, J.

    2004-01-01

    Approximately 1,000 million infections with dengue viruses are estimated to occur annually. The majority of the cases develop mild disease, whereas only small proportion of the infected individuals develop severe hemorrhagic manifestations at the end of the acute phase of illness. In this study, the

  3. Dengue Virus Infection of Aedes aegypti Requires a Putative Cysteine Rich Venom Protein.

    Directory of Open Access Journals (Sweden)

    Berlin Londono-Renteria

    2015-10-01

    Full Text Available Dengue virus (DENV is a mosquito-borne flavivirus that causes serious human disease and mortality worldwide. There is no specific antiviral therapy or vaccine for DENV infection. Alterations in gene expression during DENV infection of the mosquito and the impact of these changes on virus infection are important events to investigate in hopes of creating new treatments and vaccines. We previously identified 203 genes that were ≥5-fold differentially upregulated during flavivirus infection of the mosquito. Here, we examined the impact of silencing 100 of the most highly upregulated gene targets on DENV infection in its mosquito vector. We identified 20 genes that reduced DENV infection by at least 60% when silenced. We focused on one gene, a putative cysteine rich venom protein (SeqID AAEL000379; CRVP379, whose silencing significantly reduced DENV infection in Aedes aegypti cells. Here, we examine the requirement for CRVP379 during DENV infection of the mosquito and investigate the mechanisms surrounding this phenomenon. We also show that blocking CRVP379 protein with either RNAi or specific antisera inhibits DENV infection in Aedes aegypti. This work identifies a novel mosquito gene target for controlling DENV infection in mosquitoes that may also be used to develop broad preventative and therapeutic measures for multiple flaviviruses.

  4. Comparative Infectivity Determinations of Dengue Virus Vaccine Candidates in Rhesus Monkeys, Mosquitoes, and Cell Cultures

    Science.gov (United States)

    1993-01-28

    34 are required for the evaluation of these vaccine candidates. RE: DAMDI7-89-C-9175 Page 16 REFERENCES 1. Sabin AB, Sclesinger RW, 1945. Production of...AD-A261 892 CONTRACT NO: DAMD17-89-C-9 175 \\II\\IllI\\I\\I1\\\\~il\\ TITLE: COMPARATIVE INFECTIVITY DETERMINATIONS OF DENGUE VIRUS VACCINE CANDIDATES IN... Vaccine Candidates in Rhesus Monkeys, 63002A Mosquitoes, and Cell Cultures 3M263002D870 AC 6. AUTHOR(S) DA335475 Edmundo Kraiselburd 7. PERFORMING

  5. Translation efficiency determines differences in cellular infection among dengue virus type 2 strains

    International Nuclear Information System (INIS)

    Edgil, Dianna; Diamond, Michael S.; Holden, Katherine L.; Paranjape, Suman M.; Harris, Eva

    2003-01-01

    We have investigated the molecular basis for differences in the ability of natural variants of dengue virus type 2 (DEN2) to replicate in primary human cells. The rates of virus binding, virus entry, input strand translation, and RNA stability of low-passage Thai and Nicaraguan and prototype DEN2 strains were compared. All strains exhibited equivalent binding, entry, and uncoating, and displayed comparable stability of positive strand viral RNA over time in primary cells. However, the low-passage Nicaraguan isolates were much less efficient in their ability to translate viral proteins. Sequence analysis of the full-length low-passage Nicaraguan and Thai viral genomes identified specific differences in the 3' untranslated region (3'UTR). Substitution of the different sequences into chimeric RNA reporter constructs demonstrated that the changes in the 3'UTR directly affected the efficiency of viral translation. Thus, differences in infectivity among closely related DEN2 strains correlate with efficiency of translation of input viral RNA

  6. Plasmablasts During Acute Dengue Infection Represent a Small Subset of a Broader Virus-specific Memory B Cell Pool

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    Ramapraba Appanna

    2016-10-01

    Full Text Available Dengue is endemic in tropical countries worldwide and the four dengue virus serotypes often co-circulate. Infection with one serotype results in high titers of cross-reactive antibodies produced by plasmablasts, protecting temporarily against all serotypes, but impairing protective immunity in subsequent infections. To understand the development of these plasmablasts, we analyzed virus-specific B cell properties in patients during acute disease and at convalescence. Plasmablasts were unrelated to classical memory cells expanding in the blood during early recovery. We propose that only a small subset of memory B cells is activated as plasmablasts during repeat infection and that plasmablast responses are not representative of the memory B cell repertoire after dengue infection.

  7. Dengue virus markers of virulence and pathogenicity

    OpenAIRE

    Rico-Hesse, Rebeca

    2009-01-01

    The increased spread of dengue fever and its more severe form, dengue hemorrhagic fever, have made the study of the mosquito-borne dengue viruses that cause these diseases a public health priority. Little is known about how or why the four different (serotypes 1–4) dengue viruses cause pathology in humans only, and there have been no animal models of disease to date. Therefore, there are no vaccines or antivirals to prevent or treat infection and mortality rates of dengue hemorrhagic fever pa...

  8. Three cases of imported dengue virus infection from Madeira to Belgium, 2012.

    Science.gov (United States)

    Cnops, Lieselotte; Franco, Leticia; Van Meensel, Britt; Van den Ende, Jef; Paz Sanchez-Seco, Maria; Van Esbroeck, Marjan

    2014-01-01

    We report three laboratory-confirmed dengue virus (DENV) infections imported to Belgium by travelers returning from Madeira (Portugal). Despite the use of a mosquito-repellent spray as reported by two patients, the infection could not be prevented. Diagnosis was made by antigen detection and real-time reverse transcriptase polymerase chain reaction (RT-PCR) in two cases and by serology 1 month after onset of symptoms in a third one. The responsible virus was identified as DENV serotype 1, American/African genotype (genotype V). The close relationship to isolates from Colombia supports the previous findings that a South American strain originated the outbreak in Madeira in 2012. © 2014 International Society of Travel Medicine.

  9. Correlation of serotype-specific dengue virus infection with clinical manifestations.

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    Eric S Halsey

    Full Text Available Disease caused by the dengue virus (DENV is a significant cause of morbidity throughout the world. Although prior research has focused on the association of specific DENV serotypes (DENV-1, DENV-2, DENV-3, and DENV-4 with the development of severe outcomes such as dengue hemorrhagic fever and dengue shock syndrome, relatively little work has correlated other clinical manifestations with a particular DENV serotype. The goal of this study was to estimate and compare the prevalence of non-hemorrhagic clinical manifestations of DENV infection by serotype.Between the years 2005-2010, individuals with febrile disease from Peru, Bolivia, Ecuador, and Paraguay were enrolled in an outpatient passive surveillance study. Detailed information regarding clinical signs and symptoms, as well as demographic information, was collected. DENV infection was confirmed in patient sera with polyclonal antibodies in a culture-based immunofluorescence assay, and the infecting serotype was determined by serotype-specific monoclonal antibodies. Differences in the prevalence of individual and organ-system manifestations were compared across DENV serotypes. One thousand seven hundred and sixteen individuals were identified as being infected with DENV-1 (39.8%, DENV-2 (4.3%, DENV-3 (41.5%, or DENV-4 (14.4%. When all four DENV serotypes were compared with each other, individuals infected with DENV-3 had a higher prevalence of musculoskeletal and gastrointestinal manifestations, and individuals infected with DENV-4 had a higher prevalence of respiratory and cutaneous manifestations.Specific clinical manifestations, as well as groups of clinical manifestations, are often overrepresented by an individual DENV serotype.

  10. Correlation of Serotype-Specific Dengue Virus Infection with Clinical Manifestations

    Science.gov (United States)

    Halsey, Eric S.; Marks, Morgan A.; Gotuzzo, Eduardo; Fiestas, Victor; Suarez, Luis; Vargas, Jorge; Aguayo, Nicolas; Madrid, Cesar; Vimos, Carlos; Kochel, Tadeusz J.; Laguna-Torres, V. Alberto

    2012-01-01

    Background Disease caused by the dengue virus (DENV) is a significant cause of morbidity throughout the world. Although prior research has focused on the association of specific DENV serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) with the development of severe outcomes such as dengue hemorrhagic fever and dengue shock syndrome, relatively little work has correlated other clinical manifestations with a particular DENV serotype. The goal of this study was to estimate and compare the prevalence of non-hemorrhagic clinical manifestations of DENV infection by serotype. Methodology and Principal Findings Between the years 2005–2010, individuals with febrile disease from Peru, Bolivia, Ecuador, and Paraguay were enrolled in an outpatient passive surveillance study. Detailed information regarding clinical signs and symptoms, as well as demographic information, was collected. DENV infection was confirmed in patient sera with polyclonal antibodies in a culture-based immunofluorescence assay, and the infecting serotype was determined by serotype-specific monoclonal antibodies. Differences in the prevalence of individual and organ-system manifestations were compared across DENV serotypes. One thousand seven hundred and sixteen individuals were identified as being infected with DENV-1 (39.8%), DENV-2 (4.3%), DENV-3 (41.5%), or DENV-4 (14.4%). When all four DENV serotypes were compared with each other, individuals infected with DENV-3 had a higher prevalence of musculoskeletal and gastrointestinal manifestations, and individuals infected with DENV-4 had a higher prevalence of respiratory and cutaneous manifestations. Conclusions/Significance Specific clinical manifestations, as well as groups of clinical manifestations, are often overrepresented by an individual DENV serotype. PMID:22563516

  11. Functionality of Dengue Virus Specific Memory T Cell Responses in Individuals Who Were Hospitalized or Who Had Mild or Subclinical Dengue Infection

    Science.gov (United States)

    Jeewandara, Chandima; Adikari, Thiruni N.; Gomes, Laksiri; Fernando, Samitha; Fernando, R. H.; Perera, M. K. T.; Ariyaratne, Dinuka; Kamaladasa, Achala; Salimi, Maryam; Prathapan, Shamini

    2015-01-01

    Background Although antibody responses to dengue virus (DENV) in naturally infected individuals have been extensively studied, the functionality of DENV specific memory T cell responses in relation to clinical disease severity is incompletely understood. Methodology/Principal findings Using ex vivo IFNγ ELISpot assays, and by determining cytokines produced in ELISpot supernatants, we investigated the functionality of DENV-specific memory T cell responses in a large cohort of individuals from Sri Lanka (n=338), who were naturally infected and were either hospitalized due to dengue or had mild or sub clinical dengue infection. We found that T cells of individuals with both past mild or sub clinical dengue infection and who were hospitalized produced multiple cytokines when stimulated with DENV-NS3 peptides. However, while DENV-NS3 specific T cells of those with mild/sub clinical dengue infection were more likely to produce only granzyme B (p=0.02), those who were hospitalized were more likely to produce both TNFα and IFNγ (p=0.03) or TNFα alone. We have also investigated the usefulness of a novel T cell based assay, which can be used to determine the past infecting DENV serotype. 92.4% of DENV seropositive individuals responded to at least one DENV serotype of this assay and none of the seronegatives responded. Individuals who were seronegative, but had received the Japanese encephalitis vaccine too made no responses, suggesting that the peptides used in this assay did not cross react with the Japanese encephalitis virus. Conclusions/significance The types of cytokines produced by DENV-specific memory T cells appear to influence the outcome of clinical disease severity. The novel T cell based assay, is likely to be useful in determining the past infecting DENV serotype in immune-epidemiological studies and also in dengue vaccine trials. PMID:25875020

  12. First record in America of Aedes albopictus naturally infected with dengue virus during the 1995 outbreak at Reynosa, Mexico.

    Science.gov (United States)

    Ibáñez-Bernal, S; Briseño, B; Mutebi, J P; Argot, E; Rodríguez, G; Martínez-Campos, C; Paz, R; de la Fuente-San Román, P; Tapia-Conyer, R; Flisser, A

    1997-10-01

    Mosquito collections were conducted during a dengue outbreak in Reynosa, Tamaulipas, Mexico, July-December 1995. A total of 6694 adult mosquitoes (four genera and nine species) were captured, of which 2986 (78.3% females and 21.7% males) were Aedes albopictus and 2339 (39.7% females and 60.3% males) were Ae.aegypti. These two species comprised 84.2% of the total collection. Specimens were grouped into pools, nearly 50% of them processed for detection of virus by cythopathic effect in C6-36 and VERO cell cultures and by haemagglutination test. Five pools gave positive haemagglutination reactions and were examined by immunofluorescence using monoclonal antibodies to flavivirus and to dengue virus. One pool of ten Ae.albopictus males was positive for dengue virus: serotypes 2 and 3 were identified by serotype-specific monoclonal antibodies and confirmed by RT-PCR. This is the first report of Ae.albopictus naturally infected with dengue virus in America. Also, it is the very first time Ae.albopictus males have been found infected with dengue virus in the wild.

  13. A lethal model of disseminated dengue virus type 1 infection in AG129 mice.

    Science.gov (United States)

    Milligan, Gregg N; Sarathy, Vanessa V; White, Mellodee M; Greenberg, M Banks; Campbell, Gerald A; Pyles, Richard B; Barrett, Alan D T; Bourne, Nigel

    2017-10-01

    The mosquito-borne disease dengue is caused by four serologically and genetically related flaviviruses termed DENV-1 to DENV-4. Dengue is a global public health concern, with both the geographical range and burden of disease increasing rapidly. Clinically, dengue ranges from a relatively mild self-limiting illness to a severe life-threatening and sometimes fatal disease. Infection with one DENV serotype produces life-long homotypic immunity, but incomplete and short-term heterotypic protection. The development of small-animal models that recapitulate the characteristics of the disseminated disease seen clinically has been difficult, slowing the development of vaccines and therapeutics. The AG129 mouse (deficient in interferon alpha/beta and gamma receptor signalling) has proven to be valuable for this purpose, with the development of models of disseminated DENV-2,-3 and -4 disease. Recently, a DENV-1 AG129 model was described, but it requires antibody-dependent enhancement (ADE) to produce lethality. Here we describe a new AG129 model utilizing a non-mouse-adapted DENV-1 strain, West Pacific 74, that does not require ADE to induce lethal disease. Following high-titre intraperitoneal challenge, animals experience a virus infection with dissemination to multiple visceral tissues, including the liver, spleen and intestine. The animals also become thrombocytopenic, but vascular leakage is less prominent than in AG129 models with other DENV serotypes. Taken together, our studies demonstrate that this model is an important addition to dengue research, particularly for understanding the pathological basis of the disease between DENV serotypes and allowing the full spectrum of activity to test comparisons for putative vaccines and antivirals.

  14. Dengue viruses – an overview

    Directory of Open Access Journals (Sweden)

    Anne Tuiskunen Bäck

    2013-08-01

    Full Text Available Dengue viruses (DENVs cause the most common arthropod-borne viral disease in man with 50–100 million infections per year. Because of the lack of a vaccine and antiviral drugs, the sole measure of control is limiting the Aedes mosquito vectors. DENV infection can be asymptomatic or a self-limited, acute febrile disease ranging in severity. The classical form of dengue fever (DF is characterized by high fever, headache, stomach ache, rash, myalgia, and arthralgia. Severe dengue, dengue hemorrhagic fever (DHF, and dengue shock syndrome (DSS are accompanied by thrombocytopenia, vascular leakage, and hypotension. DSS, which can be fatal, is characterized by systemic shock. Despite intensive research, the underlying mechanisms causing severe dengue is still not well understood partly due to the lack of appropriate animal models of infection and disease. However, even though it is clear that both viral and host factors play important roles in the course of infection, a fundamental knowledge gap still remains to be filled regarding host cell tropism, crucial host immune response mechanisms, and viral markers for virulence.

  15. Dengue Virus Infection Differentially Regulates Endothelial Barrier Function over Time through Type I Interferon Effects

    Science.gov (United States)

    Liu, Ping; Woda, Marcia; Ennis, Francis A.; Libraty, Daniel H.

    2013-01-01

    Background The morbidity and mortality resulting from dengue hemorrhagic fever (DHF) are largely caused by endothelial barrier dysfunction and a unique vascular leakage syndrome. The mechanisms that lead to the location and timing of vascular leakage in DHF are poorly understood. We hypothesized that direct viral effects on endothelial responsiveness to inflammatory and angiogenesis mediators can explain the DHF vascular leakage syndrome. Methods We used an in vitro model of human endothelium to study the combined effects of dengue virus (DENV) type 2 (DENV2) infection and inflammatory mediators on paracellular macromolecule permeability over time. Results Over the initial 72 h after infection, DENV2 suppressed tumor necrosis factor (TNF)–α–mediated hyperpermeability in human umbilical vein endothelial cell (HUVEC) monolayers. This suppressive effect was mediated by type I interferon (IFN). By 1 week, TNF-α stimulation of DENV2-infected HUVECs synergistically increased cell cycling, angiogenic changes, and macromolecule permeability. This late effect could be prevented by the addition of exogenous type I IFN. Conclusions DENV infection of primary human endothelial cells differentially modulates TNF-α–driven angiogenesis and hyperpermeability over time. Type I IFN plays a central role in this process. Our findings suggest a rational model for the DHF vascular leakage syndrome. PMID:19530939

  16. Neutralizing and non-neutralizing monoclonal antibodies against dengue virus E protein derived from a naturally infected patient

    Directory of Open Access Journals (Sweden)

    Isern Sharon

    2010-02-01

    Full Text Available Abstract Background Antibodies produced in response to infection with any of the four serotypes of dengue virus generally provide homotypic immunity. However, prior infection or circulating maternal antibodies can also mediate a non-protective antibody response that can enhance the course of disease in a subsequent heterotypic infection. Naturally occurring human monoclonal antibodies can help us understand the protective and pathogenic roles of the humoral immune system in dengue virus infection. Results Epstein-Barr Virus (EBV transformation of B cells isolated from the peripheral blood of a human subject with previous dengue infection was performed. B cell cultures were screened by ELISA for antibodies to dengue (DENV envelope (E protein. ELISA positive cultures were cloned by limiting dilution. Three IgG1 human monoclonal antibodies (HMAbs were purified and their binding specificity to E protein was verified by ELISA and biolayer interferometry. Neutralization and enhancement assays were conducted in epithelial and macrophage-like cell lines, respectively. All three HMAbs bound to E from at least two of the four DENV serotypes, one of the HMAbs was neutralizing, and all were able to enhance DENV infection. Conclusions HMAbs against DENV can be successfully generated by EBV transformation of B cells from patients at least two years after naturally acquired DENV infections. These antibodies show different patterns of cross-reactivity, neutralizing, and enhancement activity.

  17. Acute disseminated encephalomyelitis in dengue viral infection.

    Science.gov (United States)

    Wan Sulaiman, Wan Aliaa; Inche Mat, Liyana Najwa; Hashim, Hasnur Zaman; Hoo, Fan Kee; Ching, Siew Mooi; Vasudevan, Ramachandran; Mohamed, Mohd Hazmi; Basri, Hamidon

    2017-09-01

    Dengue is the most common arboviral disease affecting many countries worldwide. An RNA virus from the flaviviridae family, dengue has four antigenically distinct serotypes (DEN-1-DEN-4). Neurological involvement in dengue can be classified into dengue encephalopathy immune-mediated syndromes, encephalitis, neuromuscular or dengue muscle dysfunction and neuro-ophthalmic involvement. Acute disseminated encephalomyelitis (ADEM) is an immune mediated acute demyelinating disorder of the central nervous system following recent infection or vaccination. This monophasic illness is characterised by multifocal white matter involvement. Many dengue studies and case reports have linked ADEM with dengue virus infection but the association is still not clear. Therefore, this article is to review and discuss concerning ADEM in dengue as an immune-medicated neurological complication; and the management strategy required based on recent literature. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. RNAi: antiviral therapy against dengue virus.

    Science.gov (United States)

    Idrees, Sobia; Ashfaq, Usman A

    2013-03-01

    Dengue virus infection has become a global threat affecting around 100 countries in the world. Currently, there is no licensed antiviral agent available against dengue. Thus, there is a strong need to develop therapeutic strategies that can tackle this life threatening disease. RNA interference is an important and effective gene silencing process which degrades targeted RNA by a sequence specific process. Several studies have been conducted during the last decade to evaluate the efficiency of siRNA in inhibiting dengue virus replication. This review summarizes siRNAs as a therapeutic approach against dengue virus serotypes and concludes that siRNAs against virus and host genes can be next generation treatment of dengue virus infection.

  19. Dengue virus infection in a French traveller to the hilly region of Nepal in 2015: a case report.

    Science.gov (United States)

    Gupta, Birendra Prasad; Adhikari, Anurag; Rauniyar, Ramanuj; Kurmi, Roshan; Upadhya, Bishnu Prasad; Jha, Bimlesh Kumar; Pandey, Basudev; Das Manandhar, Krishna

    2016-03-21

    Dengue viral infections are known to pose a significant risk during travel to tropical regions, but it is surprising to find dengue transmission in the hilly region of Nepal, which is over 1800mtr above sea level. A 43-year-old Caucasian female traveler from France presented with fever and abdominal pain following a diarrheal illness while visiting the central hilly region of Nepal. Over the course of 9 days, she developed fever, body aches, and joint pain, with hemorrhagic manifestation. She was hospitalized in India and treated with supportive care, with daily monitoring of her platelets. An assessment by enzyme-linked immunosorbent assay showed that she was positive for dengue non-structural protein 1. Upon her return to France, dengue virus was confirmed by reverse transcriptase-polymerase chain reaction. The district where this dengue case was reported is in the hilly region of Nepal, neighboring the capital city Kathmandu. To the best of our knowledge, there has previously been no dengue cases reported from the district. This study is important because it aims to establish a potential region of dengue virus circulation not only in the tropics, but also in the subtropics as well, which in Nepal may exceed elevations of 1800mtr. This recent case report has raised alarm among concerned health personnel, researchers, and organizations that this infectious disease is now on the way to becoming established in a temperate climate.

  20. FEVER AS INDICATOR TO SECONDARY INFECTION IN DENGUE VIRAL INFECTION

    Directory of Open Access Journals (Sweden)

    Soegeng Soegijanto

    2018-04-01

    Full Text Available Dengue Virus Infections are distributed in tropical and sub-tropical regions and transmitted by the mosquitoes such as Aedes aegypti and Aedes albopictus. Dengue virus can cause dengue fever, dengue hemorrhagic fever and dengue shock syndrome or dengue and severe dengue classified by World Health Organization. Beside it concurrent infection virus salmonella had been found some cases who showed fever more than 7 days. Concurrent infection with two agents can result in an illness having overlapping symptoms creating a diagnostic dilemma for treating physician, such as dengue fever with typhoid fever. The aim of this research is detection of dengue virus and secondary infection with Salmonella typhi in patients suspected dengue virus infection. Detection of dengue virus and Salmonella typhi using immunochromatography test such as NS1, IgG/IgM for dengue virus infection, and IgM/IgG Salmonella and blood culture. The fifty children with dengue virus infection came to Soerya hospital and 17 cases suspected dengue virus infection, five cases showed a positive NS1 on the second day of fever and one case concurrent with clinical manifestation of convulsi on the third days of fever there were five cases only showed positive. It was showed in this study that on the fourth to six day of fever in dengue virus infection accompanied by antibody IgM & IgG dengue. There were 12 cases showed the clinical manifestation of concurrent dengue viral infection and Salmonella, all of them showed a mild clinical manifestation and did not show plasma leakage and shock. In this study we found the length of stay of concurrent Dengue Virus Infection and Salmonella infection is more than 10 days. These patients were also more likely to have co-existing haemodynamic disturbances and bacterial septicaemia which would have required treatment with inotropes and antibiotics. This idea is very important to make update dengue viral management to decrease mortality in outbreak try to

  1. Antibody Prophylaxis Against Dengue Virus 2 Infection in Non-Human Primates.

    Science.gov (United States)

    Simmons, Monika; Putnak, Robert; Sun, Peifang; Burgess, Timothy; Marasco, Wayne A

    2016-11-02

    Passive immunization with anti-dengue virus (DENV) immune serum globulin (ISG) or monoclonal antibodies (Mabs) may serve to supplement or replace vaccination for short-term dengue immune prophylaxis. In the present study, we sought to establish proof-of-concept by evaluating several DENV-neutralizing antibodies for their ability to protect rhesus macaques against viremia following live virus challenge, including human anti-dengue ISG, and a human Mab (Mab11/wt) and its genetically engineered variant (Mab11/mutFc) that is unable to bind to cells with Fc gamma receptors (FcγR) and potentiate antibody-dependent enhancement (ADE). In the first experiment, groups of animals received ISG or Mab11/wt at low doses (3-10 mg/kg) or a saline control followed by challenge with DENV-2 at day 10 or 30. After passive immunization, only low-titered circulating virus-neutralizing antibody titers were measured in both groups, which were undetectable by day 30. After challenge at day 10, a reduction in viremia duration compared with the control was seen only in the ISG group (75%). However, after a day 30 challenge, no reduction in viremia was observed in both immunized groups. In a second experiment to test the effect of higher antibody doses on short-term protection, groups received either ISG, Mab11/wt, Mab11/mutFc (each at 25 mg/kg) or saline followed by challenge with DENV-2 on day 10. Increased virus-neutralizing antibody titers were detected in all groups at day 5 postinjection, with geometric mean titers (GMTs) of 464 (ISG), 313 (Mab11/wt), and 309 (Mab11/mutFc). After challenge, there was complete protection against viremia in the group that received ISG, and a reduction in viremia duration of 89% and 83% in groups that received Mab11/wt and Mab11/mutFc, respectively. An in vitro ADE assay in Fcγ receptor-bearing K562 cells with sera collected immediately before challenge showed increased DENV-2 infection levels in the presence of both ISG and Mab11/wt, which peaked at a

  2. Detection of Immune-Complex Dissociated Nonstructural-1 (NS-1) Antigen in Patients with Acute Dengue Virus Infections

    NARCIS (Netherlands)

    P. Koraka (Penelope); C.P. Burghoorn-Maas; A. Falconar; T.E. Setiati (Tatty); K. Djamiatun; J. Groen (Jan); A.D.M.E. Osterhaus (Albert)

    2003-01-01

    textabstractAccurate and timely diagnosis of dengue virus (DEN) infections is essential for the differential diagnosis of patients with febrile illness and hemorrhagic fever. In the present study, the diagnostic value of a newly developed immune-complex dissociated nonstructural-1 (NS-1) antigen dot

  3. Prevalence of dengue and chikungunya virus infections in north-eastern Tanzania

    DEFF Research Database (Denmark)

    Kajeguka, Debora C; Kaaya, Robert D; Mwakalinga, Steven

    2016-01-01

    BACKGROUND: In spite of increasing reports of dengue and chikungunya activity in Tanzania, limited research has been done to document the general epidemiology of dengue and chikungunya in the country. This study aimed at determining the sero-prevalence and prevalence of acute infections of dengue......-like symptoms at health facilities at Bondo dispensary (Bondo, Tanga), Hai hospital (Hai, Kilimanjaro) and TPC hospital (Lower Moshi). Participants who were malaria negative using rapid diagnostic tests (mRDT) were screened for sero-positivity towards dengue and chikungunya Immunoglobulin G and M (IgG and Ig......M) using ELISA-based kits. Participants with specific symptoms defined as probable dengue and/or chikungunya by WHO (fever and various combinations of symptoms such as headache, rash, nausea/vomit, and joint pain) were further screened for acute dengue and chikungunya infections by PCR. RESULTS: Out...

  4. Single-virus tracking approach to reveal the interaction of Dengue virus with autophagy during the early stage of infection

    Science.gov (United States)

    Chu, Li-Wei; Huang, Yi-Lung; Lee, Jin-Hui; Huang, Long-Ying; Chen, Wei-Jun; Lin, Ya-Hsuan; Chen, Jyun-Yu; Xiang, Rui; Lee, Chau-Hwang; Ping, Yueh-Hsin

    2014-01-01

    Dengue virus (DENV) is one of the major infectious pathogens worldwide. DENV infection is a highly dynamic process. Currently, no antiviral drug is available for treating DENV-induced diseases since little is known regarding how the virus interacts with host cells during infection. Advanced molecular imaging technologies are powerful tools to understand the dynamics of intracellular interactions and molecular trafficking. This study exploited a single-virus particle tracking technology to address whether DENV interacts with autophagy machinery during the early stage of infection. Using confocal microscopy and three-dimensional image analysis, we showed that DENV triggered the formation of green fluorescence protein-fused microtubule-associated protein 1A/1B-light chain 3 (GFP-LC3) puncta, and DENV-induced autophagosomes engulfed DENV particles within 15-min postinfection. Moreover, single-virus particle tracking revealed that both DENV particles and autophagosomes traveled together during the viral infection. Finally, in the presence of autophagy suppressor 3-methyladenine, the replication of DENV was inhibited and the location of DENV particles spread in cytoplasma. In contrast, the numbers of newly synthesized DENV were elevated and the co-localization of DENV particles and autophagosomes was detected while the cells were treated with autophagy inducer rapamycin. Taken together, we propose that DENV particles interact with autophagosomes at the early stage of viral infection, which promotes the replication of DENV.

  5. Alterations in the Aedes aegypti transcriptome during infection with West Nile, dengue and yellow fever viruses.

    Directory of Open Access Journals (Sweden)

    Tonya M Colpitts

    2011-09-01

    Full Text Available West Nile (WNV, dengue (DENV and yellow fever (YFV viruses are (reemerging, mosquito-borne flaviviruses that cause human disease and mortality worldwide. Alterations in mosquito gene expression common and unique to individual flaviviral infections are poorly understood. Here, we present a microarray analysis of the Aedes aegypti transcriptome over time during infection with DENV, WNV or YFV. We identified 203 mosquito genes that were ≥ 5-fold differentially up-regulated (DUR and 202 genes that were ≥ 10-fold differentially down-regulated (DDR during infection with one of the three flaviviruses. Comparative analysis revealed that the expression profile of 20 DUR genes and 15 DDR genes was quite similar between the three flaviviruses on D1 of infection, indicating a potentially conserved transcriptomic signature of flaviviral infection. Bioinformatics analysis revealed changes in expression of genes from diverse cellular processes, including ion binding, transport, metabolic processes and peptidase activity. We also demonstrate that virally-regulated gene expression is tissue-specific. The overexpression of several virally down-regulated genes decreased WNV infection in mosquito cells and Aedes aegypti mosquitoes. Among these, a pupal cuticle protein was shown to bind WNV envelope protein, leading to inhibition of infection in vitro and the prevention of lethal WNV encephalitis in mice. This work provides an extensive list of targets for controlling flaviviral infection in mosquitoes that may also be used to develop broad preventative and therapeutic measures for multiple flaviviruses.

  6. 18F-FDG as an inflammation biomarker for imaging dengue virus infection and treatment response.

    Science.gov (United States)

    Chacko, Ann-Marie; Watanabe, Satoru; Herr, Keira J; Kalimuddin, Shirin; Tham, Jing Yang; Ong, Joanne; Reolo, Marie; Serrano, Raymond M F; Cheung, Yin Bun; Low, Jenny G H; Vasudevan, Subhash G

    2017-05-04

    Development of antiviral therapy against acute viral diseases, such as dengue virus (DENV), suffers from the narrow window of viral load detection in serum during onset and clearance of infection and fever. We explored a biomarker approach using 18F-fluorodeoxyglucose (18F-FDG) PET in established mouse models for primary and antibody-dependent enhancement infection with DENV. 18F-FDG uptake was most prominent in the intestines and correlated with increased virus load and proinflammatory cytokines. Furthermore, a significant temporal trend in 18F-FDG uptake was seen in intestines and selected tissues over the time course of infection. Notably, 18F-FDG uptake and visualization by PET robustly differentiated treatment-naive groups from drug-treated groups as well as nonlethal from lethal infections with a clinical strain of DENV2. Thus, 18F-FDG may serve as a novel DENV infection-associated inflammation biomarker for assessing treatment response during therapeutic intervention trials.

  7. Infection of epithelial cells with dengue virus promotes the expression of proteins favoring the replication of certain viral strains.

    Science.gov (United States)

    Martínez-Betancur, Viviana; Marín-Villa, Marcel; Martínez-Gutierrez, Marlén

    2014-08-01

    Dengue virus (DENV) is the causative agent of dengue and severe dengue. To understand better the dengue virus-host interaction, it is important to determine how the expression of cellular proteins is modified due to infection. Therefore, a comparison of protein expression was conducted in Vero cells infected with two different DENV strains, both serotype 2: DENV-2/NG (associated with dengue) and DENV-2/16681 (associated with severe dengue). The viability of the infected cells was determined, and neither strain induced cell death at 48 hr. In addition, the viral genomes and infectious viral particles were quantified, and the genome of the DENV-2/16681 strain was determined to have a higher replication rate compared with the DENV-2/NG strain. Finally, the proteins from infected and uninfected cultures were separated using two-dimensional gel electrophoresis, and the differentially expressed proteins were identified by mass spectrometry. Compared with the uninfected controls, the DENV-2/NG- and DENV-2/16681-infected cultures had five and six differentially expressed proteins, respectively. The most important results were observed when the infected cultures were compared to each other (DENV-2/NG vs. DENV-2/16681), and 18 differentially expressed proteins were identified. Based on their cellular functions, many of these proteins were linked to the increase in the replication efficiency of DENV. Among the proteins were calreticulin, acetyl coenzyme A, acetyl transferase, and fatty acid-binding protein. It was concluded that the infection of Vero cells with DENV-2/NG or DENV-2/16681 differentially modifies the expression of certain proteins, which can, in turn, facilitate infection. © 2013 Wiley Periodicals, Inc.

  8. The Influence of Dengue Virus Serotype-2 Infection on Aedes aegypti (Diptera: Culicidae) Motivation and Avidity to Blood Feed

    OpenAIRE

    Maciel-de-Freitas, Rafael; Sylvestre, Gabriel; Gandini, Mariana; Koella, Jacob C.

    2013-01-01

    BACKGROUND: Dengue virus (DENV) is transmitted by Aedes aegypti, a species that lives in close association with human dwellings. The behavior of DENV-infected mosquitoes needs further investigation, especially regarding the potential influence of DENV on mosquito biting motivation and avidity. METHODOLOGY/PRINCIPAL FINDINGS: We orally challenged 4-5 day-old Ae. aegypti females with a low passage DENV serotype -2 (DENV-2) to test whether the virus influences motivation to feed (the likelihood ...

  9. Dengue virus transovarial transmission by Aedes aegypti

    Directory of Open Access Journals (Sweden)

    Monica Dwi Hartanti

    2016-02-01

    Full Text Available Dengue is a disease that is caused by dengue virus and transmitted to humans through the bite of infected Aedes mosquitoes, especially Aedes aegypti. The disease is hyper-endemic in Southeast Asia, where a more severe form, dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS, is a major public health concern. The purpose of the present study was to find evidence of dengue virus transovarial transmision in local vectors in Jakarta. Fifteen Aedes larvae were collected in 2009 from two areas in Tebet subdistrict in South Jakarta, namely one area with the highest and one with the lowest DHF prevalence. All mosquitoes were reared inside two cages in the laboratory, eight mosquitoes in one cage and seven mosquitoes in another cage and given only sucrose solution as their food. The results showed that 20% of the mosquitoes were positive for dengue virus. Dengue virus detection with an immunohistochemical method demonstrated the occurrence of transovarial transmission in local DHF vectors in Tebet subdistrict. Transovarial dengue infection in Ae.aegypti larvae appeared to maintain or enhance epidemics. Further research is needed to investigate the relation of dengue virus transovarial transmission with DHF endemicity in Jakarta.

  10. Dengue virus transovarial transmission by Aedes aegypti

    Directory of Open Access Journals (Sweden)

    Monica Dwi Hartanti

    2010-08-01

    Full Text Available Dengue is a disease that is caused by dengue virus and transmitted to humans through the bite of infected Aedes mosquitoes, especially Aedes aegypti. The disease is hyper-endemic in Southeast Asia, where a more severe form, dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS, is a major public health concern. The purpose of the present study was to find evidence of dengue virus transovarial transmision in local vectors in Jakarta. Fifteen Aedes larvae were collected in 2009 from two areas in Tebet subdistrict in South Jakarta, namely one area with the highest and one with the lowest DHF prevalence. All mosquitoes were reared inside two cages in the laboratory, eight mosquitoes in one cage and seven mosquitoes in another cage and given only sucrose solution as their food. The results showed that 20% of the mosquitoes were positive for dengue virus. Dengue virus detection with an immunohistochemical method demonstrated the occurrence of transovarial transmission in local DHF vectors in Tebet subdistrict. Transovarial dengue infection in Ae.aegypti larvae appeared to maintain or enhance epidemics. Further research is needed to investigate the relation of dengue virus transovarial transmission with DHF endemicity in Jakarta.

  11. T-cell Responses in Individuals Infected with Zika Virus and in Those Vaccinated Against Dengue Virus

    Directory of Open Access Journals (Sweden)

    Dominic Paquin-Proulx

    2017-06-01

    Full Text Available Background: The outbreak of Zika virus (ZIKV infection in Brazil has raised concerns that infection during pregnancy could cause microcephaly and other severe neurodevelopmental malformations in the fetus. The mechanisms by which ZIKV causes fetal abnormalities are largely unknown. The importance of pre-infection with dengue virus (DENV, or other flaviviruses endemic to Brazil, remains to be investigated. It has been reported that antibodies directed against DENV can increase ZIKV infectivity by antibody dependent enhancement (ADE, suggesting that a history of prior DENV infection might worsen the outcome of ZIKV infection. Methods: We used bioinformatics tools to design 18 peptides from the ZIKV envelope containing predicted HLA-I T-cell epitopes and investigated T-cell cross-reactivity between ZIKV-infected individuals and DENV-vaccinated subjects by IFNg ELISPOT. Results: Three peptides induced IFNg production in both ZIKV-infected subjects and in DENV-vaccinated individuals. Flow cytometry indicated that 1 ZIKV peptide induced a CD4+ T-cell response in DENV-vaccinated subjects. Conclusions: We demonstrated that vaccination against DENV induced a T-cell response against ZIKV and identified one such CD4+ T-cell epitope. The ZIKV-reactive CD4+ T cells induced by DENV vaccination and identified in this study could contribute to the appearance of cross-reactive antibodies mediating ADE.

  12. T-cell Responses in Individuals Infected with Zika Virus and in Those Vaccinated Against Dengue Virus.

    Science.gov (United States)

    Paquin-Proulx, Dominic; Leal, Fabio E; Terrassani Silveira, Cassia G; Maestri, Alvino; Brockmeyer, Claudia; Kitchen, Shannon M; Cabido, Vinicius D; Kallas, Esper G; Nixon, Douglas F

    2017-01-01

    The outbreak of Zika virus (ZIKV) infection in Brazil has raised concerns that infection during pregnancy could cause microcephaly and other severe neurodevelopmental malformations in the fetus. The mechanisms by which ZIKV causes fetal abnormalities are largely unknown. The importance of pre-infection with dengue virus (DENV), or other flaviviruses endemic to Brazil, remains to be investigated. It has been reported that antibodies directed against DENV can increase ZIKV infectivity by antibody dependent enhancement (ADE), suggesting that a history of prior DENV infection might worsen the outcome of ZIKV infection. We used bioinformatics tools to design 18 peptides from the ZIKV envelope containing predicted HLA-I T-cell epitopes and investigated T-cell cross-reactivity between ZIKV-infected individuals and DENV-vaccinated subjects by IFNγ ELISPOT. Three peptides induced IFNγ production in both ZIKV-infected subjects and in DENV-vaccinated individuals. Flow cytometry indicated that 1 ZIKV peptide induced a CD4+ T-cell response in DENV-vaccinated subjects. We demonstrated that vaccination against DENV induced a T-cell response against ZIKV and identified one such CD4+ T-cell epitope. The ZIKV-reactive CD4+ T cells induced by DENV vaccination and identified in this study could contribute to the appearance of cross-reactive antibodies mediating ADE.

  13. Transcriptome analysis of Aedes aegypti in response to mono-infections and co-infections of dengue virus-2 and chikungunya virus.

    Science.gov (United States)

    Shrinet, Jatin; Srivastava, Pratibha; Sunil, Sujatha

    2017-10-28

    Chikungunya virus (CHIKV) and Dengue virus (DENV) spread via the bite of infected Aedes mosquitoes. Both these viruses exist as co-infections in the host as well as the vector and are known to exploit their cellular machinery for their replication. While there are studies reporting the changes in Aedes transcriptome when infected with DENV and CHIKV individually, the effect both these viruses have on the mosquitoes when present as co-infections is not clearly understood. In the present study, we infected Aedes aegypti mosquitoes with DENV and CHIKV individually and as co-infection through nanoinjections. We performed high throughput RNA sequencing of the infected Aedes aegypti to understand the changes in the Aedes transcriptome during the early stages of infection, i.e., 24 h post infection and compared the transcriptome profiles during DENV and CHIKV mono-infections with that of co-infections. We identified 190 significantly regulated genes identified in CHIKV infected library, 37 genes from DENV library and 100 genes from co-infected library and they were classified into different pathways. Our study reveal that distinct pathways and transcripts are being regulated during the three types of infection states in Aedes aegypti mosquitoes. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Formation of infectious dengue virus-antibody immune complex in vivo in marmosets (Callithrix jacchus) after passive transfer of anti-dengue virus monoclonal antibodies and infection with dengue virus.

    Science.gov (United States)

    Moi, Meng Ling; Ami, Yasushi; Shirai, Kenji; Lim, Chang-Kweng; Suzaki, Yuriko; Saito, Yuka; Kitaura, Kazutaka; Saijo, Masayuki; Suzuki, Ryuji; Kurane, Ichiro; Takasaki, Tomohiko

    2015-02-01

    Infection with a dengue virus (DENV) serotype induces cross-reactive, weakly neutralizing antibodies to different dengue serotypes. It has been postulated that cross-reactive antibodies form a virus-antibody immune complex and enhance DENV infection of Fc gamma receptor (FcγR)-bearing cells. We determined whether infectious DENV-antibody immune complex is formed in vivo in marmosets after passive transfer of DENV-specific monoclonal antibody (mAb) and DENV inoculation and whether infectious DENV-antibody immune complex is detectable using FcγR-expressing cells. Marmosets showed that DENV-antibody immune complex was exclusively infectious to FcγR-expressing cells on days 2, 4, and 7 after passive transfer of each of the mAbs (mAb 4G2 and mAb 6B6C) and DENV inoculation. Although DENV-antibody immune complex was detected, contribution of the passively transferred antibody to overall viremia levels was limited in this study. The results indicate that DENV cross-reactive antibodies form DENV-antibody immune complex in vivo, which is infectious to FcγR-bearing cells but not FcγR-negative cells. © The American Society of Tropical Medicine and Hygiene.

  15. Co-Infection of Mosquitoes with Chikungunya and Dengue Viruses Reveals Modulation of the Replication of Both Viruses in Midguts and Salivary Glands of Aedes aegypti Mosquitoes.

    Science.gov (United States)

    Le Coupanec, Alain; Tchankouo-Nguetcheu, Stéphane; Roux, Pascal; Khun, Huot; Huerre, Michel; Morales-Vargas, Ronald; Enguehard, Margot; Lavillette, Dimitri; Missé, Dorothée; Choumet, Valérie

    2017-08-04

    Arthropod-borne virus (arbovirus) infections cause several emerging and resurgent infectious diseases in humans and animals. Chikungunya-affected areas often overlap with dengue-endemic areas. Concurrent dengue virus (DENV) and chikungunya virus (CHIKV) infections have been detected in travelers returning from regions of endemicity. CHIKV and DENV co-infected Aedes albopictus have also been collected in the vicinity of co-infected human cases, emphasizing the need to study co-infections in mosquitoes. We thus aimed to study the pathogen-pathogen interaction involved in these co-infections in DENV/CHIKV co-infected Aedes aegypti mosquitoes. In mono-infections, we detected CHIKV antigens as early as 4 days post-virus exposure in both the midgut (MG) and salivary gland (SG), whereas we detected DENV serotype 2 (DENV-2) antigens from day 5 post-virus exposure in MG and day 10 post-virus exposure in SG. Identical infection rates were observed for singly and co-infected mosquitoes, and facilitation of the replication of both viruses at various times post-viral exposure. We observed a higher replication for DENV-2 in SG of co-infected mosquitoes. We showed that mixed CHIKV and DENV infection facilitated viral replication in Ae. aegypti . The outcome of these mixed infections must be further studied to increase our understanding of pathogen-pathogen interactions in host cells.

  16. Investigating Potential Effects of Dengue Virus Infection and Pre-exposure to DEET on Aedes aegypti Behaviors

    Science.gov (United States)

    2016-02-05

    Investigating Potential Effects of Dengue Virus Infection and Pre-exposure to DEET on Aedes aegypti Behaviors by Victor A...exposure to DEET on Aedes aegypti Behaviors" Name of Candidate: Victor Sugiharto Doctor of Philosophy Degree February 5, 2016 DISSERTATION AND...Infection and Pre-exposure to DEET on Aedes aegypti Behaviors" is appropriately acknowledged and. beyond brief excerpts , is with the permission of

  17. Aberrant monocyte responses predict and characterize dengue virus infection in individuals with severe disease.

    Science.gov (United States)

    Yong, Yean K; Tan, Hong Y; Jen, Soe Hui; Shankar, Esaki M; Natkunam, Santha K; Sathar, Jameela; Manikam, Rishya; Sekaran, Shamala D

    2017-05-31

    Currently, several assays can diagnose acute dengue infection. However, none of these assays can predict the severity of the disease. Biomarkers that predicts the likelihood that a dengue patient will develop a severe form of the disease could permit more efficient patient triage and allows better supportive care for the individual in need, especially during dengue outbreaks. We measured 20 plasma markers i.e. IFN-γ, IL-10, granzyme-B, CX3CL1, IP-10, RANTES, CXCL8, CXCL6, VCAM, ICAM, VEGF, HGF, sCD25, IL-18, LBP, sCD14, sCD163, MIF, MCP-1 and MIP-1β in 141 dengue patients in over 230 specimens and correlate the levels of these plasma markers with the development of dengue without warning signs (DWS-), dengue with warning signs (DWS+) and severe dengue (SD). Our results show that the elevation of plasma levels of IL-18 at both febrile and defervescence phase was significantly associated with DWS+ and SD; whilst increase of sCD14 and LBP at febrile phase were associated with severity of dengue disease. By using receiver operating characteristic (ROC) analysis, the IL-18, LBP and sCD14 were significantly predicted the development of more severe form of dengue disease (DWS+/SD) (AUC = 0.768, P dengue disease. Given that the elevation IL-18, LBP and sCD14 among patients with severe form of dengue disease, our findings suggest a pathogenic role for an aberrant inflammasome and monocyte activation in the development of severe form of dengue disease.

  18. Dengue

    Science.gov (United States)

    Dengue is an infection caused by a virus. You can get it if an infected mosquito bites you. Dengue does not spread from person to person. It ... the world. Outbreaks occur in the rainy season. Dengue is rare in the United States. Symptoms include ...

  19. Defining New Therapeutics Using a More Immunocompetent Mouse Model of Antibody-Enhanced Dengue Virus Infection.

    Science.gov (United States)

    Pinto, Amelia K; Brien, James D; Lam, Chia-Ying Kao; Johnson, Syd; Chiang, Cindy; Hiscott, John; Sarathy, Vanessa V; Barrett, Alan D; Shresta, Sujan; Diamond, Michael S

    2015-09-15

    With over 3.5 billion people at risk and approximately 390 million human infections per year, dengue virus (DENV) disease strains health care resources worldwide. Previously, we and others established models for DENV pathogenesis in mice that completely lack subunits of the receptors (Ifnar and Ifngr) for type I and type II interferon (IFN) signaling; however, the utility of these models is limited by the pleotropic effect of these cytokines on innate and adaptive immune system development and function. Here, we demonstrate that the specific deletion of Ifnar expression on subsets of murine myeloid cells (LysM Cre(+) Ifnar(flox/flox) [denoted as Ifnar(f/f) herein]) resulted in enhanced DENV replication in vivo. The administration of subneutralizing amounts of cross-reactive anti-DENV monoclonal antibodies to LysM Cre(+) Ifnar(f/f) mice prior to infection with DENV serotype 2 or 3 resulted in antibody-dependent enhancement (ADE) of infection with many of the characteristics associated with severe DENV disease in humans, including plasma leakage, hypercytokinemia, liver injury, hemoconcentration, and thrombocytopenia. Notably, the pathogenesis of severe DENV-2 or DENV-3 infection in LysM Cre(+) Ifnar(f/f) mice was blocked by pre- or postexposure administration of a bispecific dual-affinity retargeting molecule (DART) or an optimized RIG-I receptor agonist that stimulates innate immune responses. Our findings establish a more immunocompetent animal model of ADE of infection with multiple DENV serotypes in which disease is inhibited by treatment with broad-spectrum antibody derivatives or innate immune stimulatory agents. Although dengue virus (DENV) infects hundreds of millions of people annually and results in morbidity and mortality on a global scale, there are no approved antiviral treatments or vaccines. Part of the difficulty in evaluating therapeutic candidates is the lack of small animal models that are permissive to DENV and recapitulate the clinical features

  20. Human antibodies to the dengue virus E-dimer epitope have therapeutic activity against Zika virus infection.

    Science.gov (United States)

    Fernandez, Estefania; Dejnirattisai, Wanwisa; Cao, Bin; Scheaffer, Suzanne M; Supasa, Piyada; Wongwiwat, Wiyada; Esakky, Prabagaran; Drury, Andrea; Mongkolsapaya, Juthathip; Moley, Kelle H; Mysorekar, Indira U; Screaton, Gavin R; Diamond, Michael S

    2017-11-01

    The Zika virus (ZIKV) epidemic has resulted in congenital abnormalities in fetuses and neonates. Although some cross-reactive dengue virus (DENV)-specific antibodies can enhance ZIKV infection in mice, those recognizing the DENV E-dimer epitope (EDE) can neutralize ZIKV infection in cell culture. We evaluated the therapeutic activity of human monoclonal antibodies to DENV EDE for their ability to control ZIKV infection in the brains, testes, placentas, and fetuses of mice. A single dose of the EDE1-B10 antibody given 3 d after ZIKV infection protected against lethality, reduced ZIKV levels in brains and testes, and preserved sperm counts. In pregnant mice, wild-type or engineered LALA variants of EDE1-B10, which cannot engage Fcg receptors, diminished ZIKV burden in maternal and fetal tissues, and protected against fetal demise. Because neutralizing antibodies to EDE have therapeutic potential against ZIKV, in addition to their established inhibitory effects against DENV, it may be possible to develop therapies that control disease caused by both viruses.

  1. Seroprevalence of Infections with Dengue, Rift Valley Fever and Chikungunya Viruses in Kenya, 2007.

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    Caroline Ochieng

    Full Text Available Arthropod-borne viruses are a major constituent of emerging infectious diseases worldwide, but limited data are available on the prevalence, distribution, and risk factors for transmission in Kenya and East Africa. In this study, we used 1,091 HIV-negative blood specimens from the 2007 Kenya AIDS Indicator Survey (KAIS 2007 to test for the presence of IgG antibodies to dengue virus (DENV, chikungunya virus (CHIKV and Rift Valley fever virus (RVFV.The KAIS 2007 was a national population-based survey conducted by the Government of Kenya to provide comprehensive information needed to address the HIV/AIDS epidemic. Antibody testing for arboviruses was performed on stored blood specimens from KAIS 2007 through a two-step sandwich IgG ELISA using either commercially available kits or CDC-developed assays. Out of the 1,091 samples tested, 210 (19.2% were positive for IgG antibodies against at least one of the three arboviruses. DENV was the most common of the three viruses tested (12.5% positive, followed by RVFV and CHIKV (4.5% and 0.97%, respectively. For DENV and RVFV, the participant's province of residence was significantly associated (P≤.01 with seropositivity. Seroprevalence of DENV and RVFV increased with age, while there was no correlation between province of residence/age and seropositivity for CHIKV. Females had twelve times higher odds of exposure to CHIK as opposed to DENV and RVFV where both males and females had the same odds of exposure. Lack of education was significantly associated with a higher odds of previous infection with either DENV or RVFV (p <0.01. These data show that a number of people are at risk of arbovirus infections depending on their geographic location in Kenya and transmission of these pathogens is greater than previously appreciated. This poses a public health risk, especially for DENV.

  2. Enhancing the sensitivity of Dengue virus serotype detection by RT-PCR among infected children in India.

    Science.gov (United States)

    Ahamed, Syed Fazil; Vivek, Rosario; Kotabagi, Shalini; Nayak, Kaustuv; Chandele, Anmol; Kaja, Murali-Krishna; Shet, Anita

    2017-06-01

    Dengue surveillance relies on reverse transcription-polymerase chain reaction (RT-PCR), for confirmation of dengue virus (DENV) serotypes. We compared efficacies of published and modified primer sets targeting envelope (Env) and capsid-premembrane (C-prM) genes for detection of circulating DENV serotypes in southern India. Acute samples from children with clinically-diagnosed dengue were used for RT-PCR testing. All samples were also subjected to dengue serology (NS1 antigen and anti-dengue-IgM/IgG rapid immunochromatographic assay). Nested RT-PCR was performed on viral RNA using three methods targeting 654bp C-prM, 511bp C-prM and 641bp Env regions, respectively. RT-PCR-positive samples were validated by population sequencing. Among 171 children with suspected dengue, 121 were dengue serology-positive and 50 were dengue serology-negative. Among 121 serology-positives, RT-PCR detected 91 (75.2%) by CprM654, 72 (59.5%) by CprM511, and 74 (61.1%) by Env641. Among 50 serology-negatives, 10 (20.0%) were detected by CprM654, 12 (24.0%) by CprM511, and 11 (22.0%) by Env641. Overall detection rate using three methods sequentially was 82.6% (100/121) among serology-positive and 40.0% (20/50) among serology-negative samples; 6.6% (8/120) had co-infection with multiple DENV serotypes. We conclude that detection of acute dengue was enhanced by a modified RT-PCR method targeting the 654bp C-prM region, and further improved by using all three methods sequentially. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Identification of RNA Binding Proteins Associated with Dengue Virus RNA in Infected Cells Reveals Temporally Distinct Host Factor Requirements.

    Directory of Open Access Journals (Sweden)

    Olga V Viktorovskaya

    2016-08-01

    Full Text Available There are currently no vaccines or antivirals available for dengue virus infection, which can cause dengue hemorrhagic fever and death. A better understanding of the host pathogen interaction is required to develop effective therapies to treat DENV. In particular, very little is known about how cellular RNA binding proteins interact with viral RNAs. RNAs within cells are not naked; rather they are coated with proteins that affect localization, stability, translation and (for viruses replication.Seventy-nine novel RNA binding proteins for dengue virus (DENV were identified by cross-linking proteins to dengue viral RNA during a live infection in human cells. These cellular proteins were specific and distinct from those previously identified for poliovirus, suggesting a specialized role for these factors in DENV amplification. Knockdown of these proteins demonstrated their function as viral host factors, with evidence for some factors acting early, while others late in infection. Their requirement by DENV for efficient amplification is likely specific, since protein knockdown did not impair the cell fitness for viral amplification of an unrelated virus. The protein abundances of these host factors were not significantly altered during DENV infection, suggesting their interaction with DENV RNA was due to specific recruitment mechanisms. However, at the global proteome level, DENV altered the abundances of proteins in particular classes, including transporter proteins, which were down regulated, and proteins in the ubiquitin proteasome pathway, which were up regulated.The method for identification of host factors described here is robust and broadly applicable to all RNA viruses, providing an avenue to determine the conserved or distinct mechanisms through which diverse viruses manage the viral RNA within cells. This study significantly increases the number of cellular factors known to interact with DENV and reveals how DENV modulates and usurps

  4. All Serotypes of Dengue Viruses Circulating in Kuala Lumpur, Malaysia

    OpenAIRE

    M.H. Chew; M.M. Rahman; J. Jelip; M.R. Hassan; I. Isahak

    2012-01-01

    Dengue is a severe disease caused by dengue virus (DENV), transmitted to human being by infected Aedes mosquitoes. It is a major public health concern in Southeast Asia due to its fatality in the form of hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The objective of the study was to isolate and identify dengue virus serotypes prevalent in endemic areas of Kuala Lumpur and Selangor in Malaysia by virus culture, indirect immunoflurecent assay and molecular techniques. A total number ...

  5. Risk factors for the incidence of dengue virus infection in preschool children.

    Science.gov (United States)

    Teixeira, Maria G; Morato, Vanessa; Barreto, Florisneide R; Mendes, Carlos M C; Barreto, Maurício L; Costa, Maria da Conceição N

    2012-11-01

    To estimate the seroincidence of dengue in children living in Salvador, Bahia, Brazil and to evaluate the factors associated.   A prospective serological survey was carried out in a sample of children 0-3 years of age. A multilevel logistic model was used to identify the determinants of seroincidence. The seroprevalence of dengue was 26.6% in the 625 children evaluated. A second survey detected an incidence of 33.2%. Multilevel logistic regression showed a statistically significant association between the seroincidence of dengue and age and the premises index. In Salvador, the dengue virus is in active circulation during early childhood; consequently, children have heterotypic antibodies and run a high risk of developing dengue haemorrhagic fever, because the sequence and intensity of the three dengue virus serotypes currently circulating in this city are very similar to those that were circulating in Rio de Janeiro, Brazil, in 2008. Therefore, the authors strongly recommend that the health authorities in cities with a similar epidemiological scenario be aware of this risk and implement improvements in health care, particularly targeting the paediatric age groups. In addition, information should be provided to the population and actions should be implemented to combat this vector. © 2012 Blackwell Publishing Ltd.

  6. Heterologous prime-boost strategy in non-human primates combining the infective dengue virus and a recombinant protein in a formulation suitable for human use.

    Science.gov (United States)

    Valdés, Iris; Hermida, Lisset; Gil, Lázaro; Lazo, Laura; Castro, Jorge; Martín, Jorge; Bernardo, Lídice; López, Carlos; Niebla, Olivia; Menéndez, Tamara; Romero, Yaremis; Sánchez, Jorge; Guzmán, María G; Guillén, Gerardo

    2010-05-01

    The aim of the present work was to test the concept of the heterologous prime-boost strategy combining an infective dengue virus with a recombinant chimeric protein carrying domain III of the envelope protein. Two studies in monkeys, combining recombinant protein PD5 (domain III of the envelope protein from dengue-2 virus, fused to the protein carrier P64k) and the infective dengue virus in the same immunization schedules were carried out. Humoral and cell-mediated immunity were evaluated. In the first study, monkeys received four doses of the protein PD5 and were subsequently infected with one dose of dengue virus. Antibody response measured after virus inoculation was significantly higher compared to that in non-primed monkeys and comparable to that elicited after two doses of infective virus. In a second study, monkeys were infected with one dose of the virus and subsequently boosted with one dose of the recombinant protein, reaching high levels of neutralizing antibodies, which were still detectable 14 months after the last immunization. In addition, the cellular immune response was also recalled. The results obtained in the present work support the approach of heterologous prime-boosting, in either order prime or boost, combining the chimeric protein PD5 (formulated in alum-CPS-A) and an infective dengue virus. The latter could potentially be replaced by an attenuated vaccine candidate. Copyright 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  7. Time-Varying, Serotype-Specific Force of Infection of Dengue Virus

    Science.gov (United States)

    2014-05-20

    Barraquer I, et al. (2011) From re-emergence to hyperendemicity: The natural history of the dengue epidemic in Brazil . PLoS Negl Trop Dis 5(1):e935. 14...Negl Trop Dis 5(9):e1322. 22. Egger JR, et al. (2008) Reconstructing historical changes in the force of infection of dengue fever in Singapore...documented outbreak of dengue in the Peruvian amazon region . Bull Pan Am Health Organ 26(3):201–207. 26. Watts DM, et al. (1999) Failure of secondary

  8. AN APPROPRIATE DIAGNOSIS OF DENGUE VIRUS INFECTION IN SOME CASES WHO HAD AND WERE BEING TREATED IN SOERYA HOSPITAL SEPANJANG – INDONESIA

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    Soegeng Soegijanto

    2015-09-01

    Full Text Available Since January 2014, Soerya Hospital has found many cases with positive result of NS or IgM and IgG Dengue. The clinical manifestations mostly were high fever with headache, vomiting and also malaise convulsion and unconsciousness. Aim of the study is to find out an appropriate diagnosis of Dengue Virus Infection. Observasional study had been done since January–April 2014 with 50 cases of dengue Virus Infection. The diagnostic procedure was made based on the WHO 2011 criteria. Result Many cases had come with fever within couple days, some of them showed convulsions. Therefore, it should be made a differential diagnosis with other disease, such as acute tonsilopharingitis, etc. The patient also had to be tested with NS1 if the patient come in the first, second and third day of fever and followed by IgM/IgG dengue on the fourth, fifth or sixth days of fever. The diagnosis of Dengue Virus Infection was made based on the WHO criteria 2011. This study showed that not all cases showed positive result of NS1 or IgM/IgG dengue on the first or second test. For the negative result, we should not think that the case is not a case of Dengue Virus Infection, especially if it happens at Aedes aegypti breeding season, the patient should be observed and performed the test again to get a proper diagnosis for Dengue Virus Infection. Monitoring clinical manifestation should always be done, to predict the appropriate diagnosis of Dengue Virus Infection.

  9. Isolation of Ancestral Sylvatic Dengue Virus Type 1, Malaysia

    Science.gov (United States)

    Teoh, Boon-Teong; Sam, Sing-Sin; Abd-Jamil, Juraina

    2010-01-01

    Ancestral sylvatic dengue virus type 1, which was isolated from a monkey in 1972, was isolated from a patient with dengue fever in Malaysia. The virus is neutralized by serum of patients with endemic DENV-1 infection. Rare isolation of this virus suggests a limited spillover infection from an otherwise restricted sylvatic cycle. PMID:21029545

  10. Neurological manifestations of dengue viral infection

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    Carod-Artal FJ

    2014-10-01

    Full Text Available Francisco Javier Carod-Artal1,21Neurology Department, Raigmore hospital, Inverness, UK; 2Universitat Internacional de Catalunya (UIC, Barcelona, Spain Abstract: Dengue is the most common mosquito-borne viral infection worldwide. There is increased evidence for dengue virus neurotropism, and neurological manifestations could make part of the clinical picture of dengue virus infection in at least 0.5%–7.4% of symptomatic cases. Neurological complications have been classified into dengue virus encephalopathy, dengue virus encephalitis, immune-mediated syndromes (acute disseminated encephalomyelitis, myelitis, Guillain–Barré syndrome, neuritis brachialis, acute cerebellitis, and others, neuromuscular complications (hypokalemic paralysis, transient benign muscle dysfunction and myositis, and dengue-associated stroke. Common neuro-ophthalmic complications are maculopathy and retinal vasculopathy. Pathogenic mechanisms include systemic complications and metabolic disturbances resulting in encephalopathy, direct effect of the virus provoking encephalitis, and postinfectious immune mechanisms causing immune-mediated syndromes. Dengue viruses should be considered as a cause of neurological disorders in endemic regions. Standardized case definitions for specific neurological complications are still needed. Keywords: encephalitis, encephalopathy, dengue fever, neurological complications

  11. Molecular determinants of dengue virus 2 envelope protein important for virus entry in FcγRIIA-mediated antibody-dependent enhancement of infection

    International Nuclear Information System (INIS)

    Chotiwan, Nunya; Roehrig, John T.; Schlesinger, Jacob J.; Blair, Carol D.; Huang, Claire Y.-H.

    2014-01-01

    Antibody-dependent enhancement (ADE) of infection may cause severe illness in patients suffering a secondary infection by a heterologous dengue virus (DENV) serotype. During ADE of infection, cross-reactive non- or poorly-neutralizing antibodies form infectious virus-Ab complexes with the newly infecting serotype and enhance virus infection by binding to the Fcγ receptors (FcγR) on FcγR-bearing cells. In this study, we determined that molecular determinants of DENV2 envelope protein critical for virus entry during non-ADE infection are also required for ADE infection mediated by FcγRIIA, and binding of virus-Ab complexes with FcγRIIA alone is not sufficient for ADE of infection. The FcγRIIA mainly plays an auxiliary role in concentrating the virus–Ab complex to the cell surface, and other primary cellular receptors are required for virus entry. Understanding the viral entry pathway in ADE of DENV infection will greatly facilitate rational designs of anti-viral therapeutics against severe dengue disease associated with ADE. - Highlights: • KKK305/307/310 in DENV2 E-DIII is critical for virus attachment in ADE and non-ADE infection. • Binding of DENV2–Ab complex with FcγRII alone is not sufficient for virus entry in ADE infection. • Other primary receptors were required for DENV2 internalization during FcγRII–mediated ADE. • G104 and L135 of DENV2 E are critical for virus-mediated membrane fusion. • DENV2 virus-mediated membrane fusion is required for both ADE and non-ADE infection

  12. Molecular determinants of dengue virus 2 envelope protein important for virus entry in FcγRIIA-mediated antibody-dependent enhancement of infection

    Energy Technology Data Exchange (ETDEWEB)

    Chotiwan, Nunya; Roehrig, John T. [Arboviral Diseases Branch, Division of Vector-Borne Disease, Centers for Disease Control and Prevention, Fort Collins, CO 80521 (United States); Schlesinger, Jacob J. [Department of Medicine, University of Rochester, Rochester, NY 14642 (United States); Blair, Carol D. [Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523 (United States); Huang, Claire Y.-H., E-mail: yxh0@cdc.gov [Arboviral Diseases Branch, Division of Vector-Borne Disease, Centers for Disease Control and Prevention, Fort Collins, CO 80521 (United States)

    2014-05-15

    Antibody-dependent enhancement (ADE) of infection may cause severe illness in patients suffering a secondary infection by a heterologous dengue virus (DENV) serotype. During ADE of infection, cross-reactive non- or poorly-neutralizing antibodies form infectious virus-Ab complexes with the newly infecting serotype and enhance virus infection by binding to the Fcγ receptors (FcγR) on FcγR-bearing cells. In this study, we determined that molecular determinants of DENV2 envelope protein critical for virus entry during non-ADE infection are also required for ADE infection mediated by FcγRIIA, and binding of virus-Ab complexes with FcγRIIA alone is not sufficient for ADE of infection. The FcγRIIA mainly plays an auxiliary role in concentrating the virus–Ab complex to the cell surface, and other primary cellular receptors are required for virus entry. Understanding the viral entry pathway in ADE of DENV infection will greatly facilitate rational designs of anti-viral therapeutics against severe dengue disease associated with ADE. - Highlights: • KKK305/307/310 in DENV2 E-DIII is critical for virus attachment in ADE and non-ADE infection. • Binding of DENV2–Ab complex with FcγRII alone is not sufficient for virus entry in ADE infection. • Other primary receptors were required for DENV2 internalization during FcγRII–mediated ADE. • G104 and L135 of DENV2 E are critical for virus-mediated membrane fusion. • DENV2 virus-mediated membrane fusion is required for both ADE and non-ADE infection.

  13. Dengue virus infection down-regulates differentiation markers in neuroblastoma cells

    OpenAIRE

    Rincón Forero, Verónica; Alvear Gómez, Diana; Solano Orjuela, Oscar; Prada-Arismendy, Jeanette; Castellanos Parra, Jaime Eduardo

    2011-01-01

    Introducción: cerca del 5% de los pacientes con dengue hemorrágico pueden presentar manifestaciones neurológicas; sin embargo, existe poca información sobre la infección directa por el virus dengue (DENV) en neuronas. Objetivo: determinar el papel del fenotipo neuronal en la infección por DENV en células de neuroblastoma SH-SY5Y inducidas o no a la diferenciación con ácido retinoico (AR). Materiales y métodos: células SH-SY5Y fueron inducidas con AR a diferenciarse e infectadas con DENV. Post...

  14. Longitudinal extensive transverse myelitis with cervical epidural haematoma following dengue virus infection.

    Science.gov (United States)

    Fong, Choong Yi; Hlaing, Chaw Su; Tay, Chee Geap; Kadir, Khairul Azmi Abdul; Goh, Khean Jin; Ong, Lai Choo

    2016-05-01

    Longitudinal extensive transverse myelitis associated with dengue infection is rare with no reported paediatric cases. We report a 12-year-old girl who presented with flaccid quadriplegia 8 days after onset of acute dengue fever. MRI spine showed T2 hyperintensity associated with epidural hematoma at C3-C6 level of the spinal cord. Transcranial magnetic brain stimulation revealed absent motor evoked potentials bilaterally. We also summarise and compare the reported cases of transverse myelitis associated with dengue infection. Immunomodulatory treatment was given which included pulse methylprednisolone, intravenous immunoglobulin and plasmapharesis. Six months post-admission, there was a good (near-complete) clinical recovery with the repeat MRI showing mild residual hyperintensity at C4 level and complete resolution of epidural haematoma. This is the first reported paediatric case of longitudinal extensive transverse myelitis following dengue infection. It is also the first to illustrate that in patients with concomitant epidural haematoma a good outcome is possible despite not having surgical decompression. Clinicians should be aware of parainfectious dengue-related longitudinal extensive transverse myelitis in children and consider prompt immunomodulatory treatment. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  15. Transmission spectroscopy of dengue viral infection

    International Nuclear Information System (INIS)

    Firdous, S; Ahmed, M; Rehman, A; Nawaz, M; Anwar, S; Murtaza, S

    2012-01-01

    We presented the rapid diagnostic test for dengue infection based on light spectrum of human blood. The transmission spectra of dengue infected whole blood samples have been recorded in ultra violet to near infrared range (400 – 800 nm) of about 30 conformed infected patients and compared to normal blood samples. Transmission spectra of dengue infected blood illustrate a strong band from 400 – 600 nm with prominant peaks at 540 and 580 nm, where is in case of normal blood below 600 nm, total absorption has been observed. These prominent peaks from 400 – 600 nm are characteristics of cells damage and dangue virus antibodies immunoglobulin G (IgG) and immunoglobulin M (IgM) produced against dengue antigen. The presented diagnostic method is non invasive, cost effective, easy and fast screening technique for dengue infected patients

  16. Molecular epidemiological and virological study of dengue virus infections in Guangzhou, China, during 2001–2010

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    Jiang Liyun

    2013-01-01

    Full Text Available Abstract Background Dengue virus (DENV infection is the most prevalent arthropod-borne viral infection in tropical and subtropical regions worldwide. Guangzhou has the ideal environment for DENV transmission and DENV epidemics have been reported in this region for more than 30 years. Methods Information for DENV infection cases in Guangzhou from 2001 to 2010 were collected and analyzed. The DENV strains were cultured and isolated from patients’ sera. Viral RNA was extracted from cell culture supernatants. cDNA was synthesized by reverse transcription PCR. Phylogenetic trees of four DENV serotypes were constructed respectively. Results In total, 2478 DENV infection cases were reported; 2143 of these (86.43% occurred during 3 months of the year: August, September and October. Of these, 2398 were local cases (96.77% and 80 were imported cases (3.23%. Among the imported cases, 69 (86.25% were from Southeast Asian countries. From the 90 isolated strains, 66.67%, 3.33%, 14.44%, and 15.56% belonged to DENV serotypes 1, 2, 3, and 4, respectively. DENV-1 was predominant in most of the years, including during 2 outbreaks in 2002 and 2006; however, none of the strains or genotypes identified in this study were found to be predominant. Interestingly, DENV strains from different years had different origins. Moreover, the strains from each year belonged to different serotypes and/or genotypes. Conclusions Southeast Asia countries were found to be the possible source of DENV in Guangzhou. These findings suggest that there is increasing diversity in DENV strains in Guangzhou, which could increase the risk of DENV outbreaks in the near future.

  17. Dengue human infection models to advance dengue vaccine development.

    Science.gov (United States)

    Larsen, Christian P; Whitehead, Stephen S; Durbin, Anna P

    2015-12-10

    Dengue viruses (DENV) currently infect approximately 400 million people each year causing millions to seek care and overwhelming the health care infrastructure in endemic areas. Vaccines to prevent dengue and therapeutics to treat dengue are not currently available. The efficacy of the most advanced candidate vaccine against symptomatic dengue in general and DENV-2 in particular was much lower than expected, despite the ability of the vaccine to induce neutralizing antibody against all four DENV serotypes. Because seroconversion to the DENV serotypes following vaccination was thought to be indicative of induced protection, these results have made it more difficult to assess which candidate vaccines should or should not be evaluated in large studies in endemic areas. A dengue human infection model (DHIM) could be extremely valuable to down-select candidate vaccines or therapeutics prior to engaging in efficacy trials in endemic areas. Two DHIM have been developed to assess the efficacy of live attenuated tetravalent (LATV) dengue vaccines. The first model, developed by the Laboratory of Infectious Diseases at the U. S. National Institutes of Health, utilizes a modified DENV-2 strain DEN2Δ30. This virus was derived from the DENV-2 Tonga/74 that caused only very mild clinical infection during the outbreak from which it was recovered. DEN2Δ30 induced viremia in 100%, rash in 80%, and neutropenia in 27% of the 30 subjects to whom it was given. The Walter Reed Army Institute of Research (WRAIR) is developing a DHIM the goal of which is to identify DENV that cause symptomatic dengue fever. WRAIR has evaluated seven viruses and has identified two that meet dengue fever criteria. Both of these models may be very useful in the evaluation and down-selection of candidate dengue vaccines and therapeutics. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Proteomic analysis reveals the enhancement of human serum apolipoprotein A-1(APO A-1) in individuals infected with multiple dengue virus serotypes.

    Science.gov (United States)

    Manchala, Nageswar Reddy; Dungdung, Ranjeet; Pilankatta, Rajendra

    2017-10-01

    Human serum protein profiling of the individual infected with multiple dengue virus serotypes for identifying the potential biomarkers and to investigate the cause for the severity of dengue virus infection. Dengue virus NS1-positive serum samples were pooled into two groups (S2 and S3) based on the molecular serotyping and number of heterotypic infections. The pooled serum samples were subjected to two-dimensional gel electrophoresis (2DGE) to identify the differentially expressed proteins. The peptide masses of upregulated protein were detected by matrix-assisted laser desorption-ionisation time-of-flight MALDI-TOF mass spectrometry and analysed by MASCOT search engine. The results were compared with the control group (S1). The commonly upregulated protein was validated by quantitative ELISA and compared with control as well as single serotypic infected samples. Based on 2DGE, total thirteen proteins were differentially upregulated in S2 and S3 groups as compared to control. Some of the upregulated proteins were involved in mediating the complement activation of immune response. The apolipoprotein A-1 (APO A-1) was upregulated in S2 and S3 groups. Upon validation, APO A-1 levels were increased in line with the number of heterotypic infection of dengue viruses. Heterotypic infection of dengue viruses upregulate the serum proteins involved in the complement pathway in the early phase of infection. There was a significant increase in the level of APO A-1 in three different serotypic infections of dengue virus as compared to control. Further, the role of APO-A1 can be explored in elucidating the mechanism of dengue pathogenesis. © 2017 John Wiley & Sons Ltd.

  19. Raman spectroscopy based screening of IgG positive and negative sera for dengue virus infection

    Science.gov (United States)

    Bilal, M.; Saleem, M.; Bial, Maria; Khan, Saranjam; Ullah, Rahat; Ali, Hina; Ahmed, M.; Ikram, Masroor

    2017-11-01

    A quantitative analysis for the screening of immunoglobulin-G (IgG) positive human sera samples is presented for the dengue virus infection. The regression model was developed using 79 samples while 20 samples were used to test the performance of the model. The R-square (r 2) value of 0.91 was found through a leave-one-sample-out cross validation method, which shows the validity of this model. This model incorporates the molecular changes associated with IgG. Molecular analysis based on regression coefficients revealed that myristic acid, coenzyme-A, alanine, arabinose, arginine, vitamin C, carotene, fumarate, galactosamine, glutamate, lactic acid, stearic acid, tryptophan and vaccenic acid are positively correlated with IgG; while amide III, collagen, proteins, fatty acids, phospholipids and fucose are negatively correlated. For blindly tested samples, an excellent agreement has been found between the model predicted, and the clinical values of IgG. The parameters, which include sensitivity, specificity, accuracy and the area under the receiver operator characteristic curve, are found to be 100%, 83.3%, 95% and 0.99, respectively, which confirms the high quality of the model.

  20. Activity of andrographolide against dengue virus.

    Science.gov (United States)

    Panraksa, Patcharee; Ramphan, Suwipa; Khongwichit, Sarawut; Smith, Duncan R

    2017-03-01

    Dengue is the most prevalent arthropod-transmitted viral illness of humans, with an estimated 100 million symptomatic infections occurring each year and more than 2.5 billion people living at risk of infection. There are no approved antiviral agents against dengue virus, and there is only limited introduction of a dengue vaccine in some countries. Andrographolide is derived from Andrographis paniculata, a medicinal plant traditionally used to treat a number of conditions including infections. The antiviral activity of andrographolide against dengue virus (DENV) serotype 2 was evaluated in two cell lines (HepG2 and HeLa) while the activity against DENV 4 was evaluated in one cell line (HepG2). Results showed that andrographolide had significant anti-DENV activity in both cell lines, reducing both the levels of cellular infection and virus output, with 50% effective concentrations (EC 50 ) for DENV 2 of 21.304 μM and 22.739 μM for HepG2 and HeLa respectively. Time of addition studies showed that the activity of andrographolide was confined to a post-infection stage. These results suggest that andrographolide has the potential for further development as an anti-viral agent for dengue virus infection. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Dengue Virus Genome Uncoating Requires Ubiquitination.

    Science.gov (United States)

    Byk, Laura A; Iglesias, Néstor G; De Maio, Federico A; Gebhard, Leopoldo G; Rossi, Mario; Gamarnik, Andrea V

    2016-06-28

    The process of genome release or uncoating after viral entry is one of the least-studied steps in the flavivirus life cycle. Flaviviruses are mainly arthropod-borne viruses, including emerging and reemerging pathogens such as dengue, Zika, and West Nile viruses. Currently, dengue virus is one of the most significant human viral pathogens transmitted by mosquitoes and is responsible for about 390 million infections every year around the world. Here, we examined for the first time molecular aspects of dengue virus genome uncoating. We followed the fate of the capsid protein and RNA genome early during infection and found that capsid is degraded after viral internalization by the host ubiquitin-proteasome system. However, proteasome activity and capsid degradation were not necessary to free the genome for initial viral translation. Unexpectedly, genome uncoating was blocked by inhibiting ubiquitination. Using different assays to bypass entry and evaluate the first rounds of viral translation, a narrow window of time during infection that requires ubiquitination but not proteasome activity was identified. In this regard, ubiquitin E1-activating enzyme inhibition was sufficient to stabilize the incoming viral genome in the cytoplasm of infected cells, causing its retention in either endosomes or nucleocapsids. Our data support a model in which dengue virus genome uncoating requires a nondegradative ubiquitination step, providing new insights into this crucial but understudied viral process. Dengue is the most significant arthropod-borne viral infection in humans. Although the number of cases increases every year, there are no approved therapeutics available for the treatment of dengue infection, and many basic aspects of the viral biology remain elusive. After entry, the viral membrane must fuse with the endosomal membrane to deliver the viral genome into the cytoplasm for translation and replication. A great deal of information has been obtained in the last decade

  2. PATHOGENESIS OF HEMORRHAGIC DUE TO DENGUE VIRUS

    Directory of Open Access Journals (Sweden)

    Arief Suseno

    2015-01-01

    Full Text Available Dengue is a viral disease that is mediated by a mosquito, which causes morbidity and mortality. Viruses can increase vascular permeability which can lead to hemorrhagic diathesis or disseminated intravascular coagulation (DIC known as dengue hemorrhagic fever (DHF. In Indonesia, dengue hemorrhagic fever (DHF are caused by dengue virus infection which was found to be endemic accompanied by an explosion of extraordinary events that appear at various specified period. The diagnosis of dengue is determined based on the criteria of the World Health Organization (WHO, 1999, which are sudden high fever accompanied by a marked tendency to hemorrhage positive tourniquet test, petechiae, ecchymosis, purpura, mucosal hemorrhagic, hematemesis or melena and thrombocytopenia. The problem that still exists today is the mechanism of thrombocytopenia in patients with varying degrees of dengue involving levels of vWF (von Willebrand factor and prostaglandin I2 (PGI2 can not be explained. The mechanism of hemorrhagic in dengue virus infections acquired as a result of thrombocytopenia, platelet disfunction decreased coagulation factors, vasculopathy with endothelial injury and disseminated intravascular coagulation (DIC.

  3. Seroprevalence of Anti-Dengue Virus 2 Serocomplex antibodies in ...

    African Journals Online (AJOL)

    Introduction: There has been a recent increase in the spread of dengue to rural areas. Rural parts of western kenya are naturally prone to mosquito-borne diseases, however, limited research has been documented on infections with dengue. This study therefore investigated the presence of antibodies against dengue virus ...

  4. piRNA Profiling of Dengue Virus Type 2-Infected Asian Tiger Mosquito and Midgut Tissues

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    Yanhai Wang

    2018-04-01

    Full Text Available The Asian tiger mosquito, Aedes albopictus, is a competent vector for the majority of arboviruses. The mosquito innate immune response is a primary determinant for arthropod-borne virus transmission, and the midgut is the first barrier to pathogen transmission. Mosquito antiviral immunity is primarily mediated by the small interfering RNA pathway. However, the roles that the P-element induced wimpy testis (PIWI-interacting RNA (piRNA pathway play in antiviral immunity in Ae. albopictus and its midgut still need further exploration. This study aimed to explore the profiles of both viral-derived and host-originated piRNAs in the whole body and midgut infected with Dengue virus 2 (DENV-2 in Ae. albopictus, and to elucidate gene expression profile differences of the PIWI protein family between adult females and their midguts. A deep sequencing-based method was used to identify and analyze small non-coding RNAs, especially the piRNA profiles in DENV-2-infected Ae. albopictus and its midgut. The top-ranked, differentially-expressed piRNAs were further validated using Stem-loop qRT-PCR. Bioinformatics analyses and reverse-transcription PCR (RT-PCR methods were used to detect PIWI protein family members, and their expression profiles. DENV-2 derived piRNAs (vpiRNA, 24–30 nts were observed in both infected Ae. albopictus and its midgut; however, only vpiRNA in the whole-body library had a weak preference for adenine at position 10 (10A in the sense molecules as a feature of secondary piRNA. These vpiRNAs were not equally distributed, instead they were derived from a few specific regions of the genome, especially several hot spots, and displayed an obvious positive strand bias. We refer to the differentially expressed host piRNAs after DENV infection as virus-induced host endogenous piRNAs (vepiRNAs. However, we found that vepiRNAs were abundant in mosquito whole-body tissue, but deficient in the midgut. A total of eleven PIWI family genes were

  5. Anti-Idiotypic Antibodies Specific to prM Monoantibody Prevent Antibody Dependent Enhancement of Dengue Virus Infection

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    Miao Wang

    2017-05-01

    Full Text Available Dengue virus (DENV co-circulates as four serotypes (DENV1-4. Primary infection only leads to self-limited dengue fever. But secondary infection with another serotype carries a higher risk of increased disease severity, causing life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS. Serotype cross-reactive antibodies facilitate DENV infection in Fc-receptor-bearing cells by promoting virus entry via Fcγ receptors (FcγR, a process known as antibody dependent enhancement (ADE. Most studies suggested that enhancing antibodies were mainly specific to the structural premembrane protein (prM of DENV. However, there is still no effective drugs or vaccines to prevent ADE. In this study, we firstly confirmed that both DENV-2 infected human sera (anti-DENV-2 and DENV-2 prM monoclonal antibody (prM mAb could significantly enhance DENV-1 infection in K562 cells. Then we developed anti-idiotypic antibodies (prM-AIDs specific to prM mAb by immunizing of Balb/c mice. Results showed that these polyclonal antibodies can dramatically reduce ADE phenomenon of DENV-1 infection in K562 cells. To further confirm the anti-ADE effect of prM-AIDs in vivo, interferon-α and γ receptor-deficient mice (AG6 were used as the mouse model for DENV infection. We found that administration of DENV-2 prM mAb indeed caused a higher DENV-1 titer as well as interleukin-10 (IL-10 and alaninea minotransferase (ALT in mice infected with DENV-1, similar to clinical ADE symptoms. But when we supplemented prM-AIDs to DENV-1 challenged AG6 mice, the viral titer, IL-10 and ALT were obviously decreased to the negative control level. Of note, the number of platelets in peripheral blood of prM-AIDs group were significantly increased at day 3 post infection with DENV-1 compared that of prM-mAb group. These results confirmed that our prM-AIDs could prevent ADE not only in vitro but also in vivo, suggested that anti-idiotypic antibodies might be a new choice to be considered to

  6. Anti-Idiotypic Antibodies Specific to prM Monoantibody Prevent Antibody Dependent Enhancement of Dengue Virus Infection.

    Science.gov (United States)

    Wang, Miao; Yang, Fan; Huang, Dana; Huang, Yalan; Zhang, Xiaomin; Wang, Chao; Zhang, Shaohua; Zhang, Renli

    2017-01-01

    Dengue virus (DENV) co-circulates as four serotypes (DENV1-4). Primary infection only leads to self-limited dengue fever. But secondary infection with another serotype carries a higher risk of increased disease severity, causing life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Serotype cross-reactive antibodies facilitate DENV infection in Fc-receptor-bearing cells by promoting virus entry via Fcγ receptors (FcγR), a process known as antibody dependent enhancement (ADE). Most studies suggested that enhancing antibodies were mainly specific to the structural premembrane protein (prM) of DENV. However, there is still no effective drugs or vaccines to prevent ADE. In this study, we firstly confirmed that both DENV-2 infected human sera (anti-DENV-2) and DENV-2 prM monoclonal antibody (prM mAb) could significantly enhance DENV-1 infection in K562 cells. Then we developed anti-idiotypic antibodies (prM-AIDs) specific to prM mAb by immunizing of Balb/c mice. Results showed that these polyclonal antibodies can dramatically reduce ADE phenomenon of DENV-1 infection in K562 cells. To further confirm the anti-ADE effect of prM-AIDs in vivo , interferon-α and γ receptor-deficient mice (AG6) were used as the mouse model for DENV infection. We found that administration of DENV-2 prM mAb indeed caused a higher DENV-1 titer as well as interleukin-10 (IL-10) and alaninea minotransferase (ALT) in mice infected with DENV-1, similar to clinical ADE symptoms. But when we supplemented prM-AIDs to DENV-1 challenged AG6 mice, the viral titer, IL-10 and ALT were obviously decreased to the negative control level. Of note, the number of platelets in peripheral blood of prM-AIDs group were significantly increased at day 3 post infection with DENV-1 compared that of prM-mAb group. These results confirmed that our prM-AIDs could prevent ADE not only in vitro but also in vivo , suggested that anti-idiotypic antibodies might be a new choice to be considered to treat

  7. Evaluation of two new commercial tests for the diagnosis of acute dengue virus infection using NS1 antigen detection in human serum.

    Science.gov (United States)

    Dussart, Philippe; Petit, Laure; Labeau, Bhety; Bremand, Laetitia; Leduc, Alexandre; Moua, David; Matheus, Séverine; Baril, Laurence

    2008-08-20

    We compared the performance of two new commercial tests for the detection of dengue NS1 protein during the clinical phase of dengue virus (DENV) infection-an immunochromatographic test allowing rapid detection of the NS1 antigen, Dengue NS1 Ag STRIP (Bio-Rad Laboratories - Marnes La Coquette, France), and a two-step sandwich-format microplate enzyme-linked immunosorbent assay (ELISA), pan-E Dengue Early ELISA (Panbio - Brisbane, Australia)-with a one-step sandwich-format microplate ELISA, the Platelia Dengue NS1 Ag test (Bio-Rad). We tested 272 serum samples from patients with dengue disease. Of these, 222 were from patients with acute infection of one of the four dengue serotypes, detected by RT-PCR and/or virus isolation. Forty-eight acute-phase serum samples from patients not infected with dengue virus were also included. The sensitivity of the Platelia Dengue NS1 Ag test on acute serum samples (n = 222) was 87.4% (95% confidence interval: 82.3% to 91.5%); that of Dengue NS1 Ag STRIP was 81.5% (95% CI: 75.8% to 86.4%) after 15 minutes and 82.4% (95% CI: 76.8% to 87.2%) after 30 minutes. Both tests had a specificity of 100% (97.5% CI, one-sided test: 92.6% to 100.0%). The pan-E Dengue Early ELISA had a sensitivity of 60.4% (95% CI: 53.4% to 66.8%) and a specificity of 97.9% (95% CI: 88.9% to 99.9%). Our findings support the use of diagnostic tools based on the NS1 antigen detection for the diagnosis of acute DENV infection. The immunochromatographic test, Dengue NS1 Ag STRIP-the first rapid diagnostic test for DENV infection-was highly sensitive and specific, and would therefore be a suitable first-line test in the field. The pan-E Dengue Early ELISA was less sensitive than the Platelia test; this two-step ELISA should be combined with DENV IgM antibody detection for the diagnosis of DENV infection.

  8. Evaluation of two new commercial tests for the diagnosis of acute dengue virus infection using NS1 antigen detection in human serum.

    Directory of Open Access Journals (Sweden)

    Philippe Dussart

    Full Text Available BACKGROUND: We compared the performance of two new commercial tests for the detection of dengue NS1 protein during the clinical phase of dengue virus (DENV infection-an immunochromatographic test allowing rapid detection of the NS1 antigen, Dengue NS1 Ag STRIP (Bio-Rad Laboratories - Marnes La Coquette, France, and a two-step sandwich-format microplate enzyme-linked immunosorbent assay (ELISA, pan-E Dengue Early ELISA (Panbio - Brisbane, Australia-with a one-step sandwich-format microplate ELISA, the Platelia Dengue NS1 Ag test (Bio-Rad. METHODS: We tested 272 serum samples from patients with dengue disease. Of these, 222 were from patients with acute infection of one of the four dengue serotypes, detected by RT-PCR and/or virus isolation. Forty-eight acute-phase serum samples from patients not infected with dengue virus were also included. RESULTS: The sensitivity of the Platelia Dengue NS1 Ag test on acute serum samples (n = 222 was 87.4% (95% confidence interval: 82.3% to 91.5%; that of Dengue NS1 Ag STRIP was 81.5% (95% CI: 75.8% to 86.4% after 15 minutes and 82.4% (95% CI: 76.8% to 87.2% after 30 minutes. Both tests had a specificity of 100% (97.5% CI, one-sided test: 92.6% to 100.0%. The pan-E Dengue Early ELISA had a sensitivity of 60.4% (95% CI: 53.4% to 66.8% and a specificity of 97.9% (95% CI: 88.9% to 99.9%. CONCLUSION: Our findings support the use of diagnostic tools based on the NS1 antigen detection for the diagnosis of acute DENV infection. The immunochromatographic test, Dengue NS1 Ag STRIP-the first rapid diagnostic test for DENV infection-was highly sensitive and specific, and would therefore be a suitable first-line test in the field. The pan-E Dengue Early ELISA was less sensitive than the Platelia test; this two-step ELISA should be combined with DENV IgM antibody detection for the diagnosis of DENV infection.

  9. Towards a Casa Segura: A Consumer Product Study of the Effect of Insecticide-Treated Curtains on Aedes aegypti and Dengue Virus Infections in the Home

    Science.gov (United States)

    Loroño-Pino, María Alba; García-Rejón, Julián E.; Machain-Williams, Carlos; Gomez-Carro, Salvador; Nuñez-Ayala, Guadalupe; del Rosario Nájera-Vázquez, Maria; Losoya, Arturo; Aguilar, Lyla; Saavedra-Rodriguez, Karla; Lozano-Fuentes, Saul; Beaty, Meaghan K.; Black, William C.; Keefe, Thomas J.; Eisen, Lars; Beaty, Barry J.

    2013-01-01

    The home, or domicile, is the principal environment for transmission of dengue virus (DENV) between humans and mosquito vectors. Community-wide distribution of insecticide-treated curtains (ITCs), mimicking vector control program-driven interventions, has shown promise to reduce DENV infections. We conducted a Casa Segura consumer product intervention study in Mérida, Mexico to determine the potential to reduce intradomicillary DENV transmission through ITC use in individual homes. Dengue virus infections in mosquitoes and in humans were reduced in homes with ITCs in one of two study subareas. Overall, ITCs reduced intradomicillary DENV transmission; ITC homes were significantly less likely to experience multiple DENV infections in humans than NTC homes. Dengue virus–infected Aedes aegypti females were reduced within the ITC homes where curtain use was highest. Some homes yielded up to nine infected Ae. aegypti females. This study provides insights regarding best practices for Casa Segura interventions to protect homes from intradomicillary DENV transmission. PMID:23732254

  10. Antiviral effect of compounds derived from the seeds of Mammea americana and Tabernaemontana cymosa on Dengue and Chikungunya virus infections.

    Science.gov (United States)

    Gómez-Calderón, Cecilia; Mesa-Castro, Carol; Robledo, Sara; Gómez, Sergio; Bolivar-Avila, Santiago; Diaz-Castillo, Fredyc; Martínez-Gutierrez, Marlen

    2017-01-18

    The transmission of Dengue virus (DENV) and Chikungunya virus (CHIKV) has increased worldwide, due in part to the lack of a specific antiviral treatment. For this reason, the search for compounds with antiviral potential, either as licensed drugs or in natural products, is a research priority. The objective of this study was to identify some of the compounds that are present in Mammea americana (M. americana) and Tabernaemontana cymosa (T. cymosa) plants and, subsequently, to evaluate their cytotoxicity in VERO cells and their potential antiviral effects on DENV and CHIKV infections in those same cells. Dry ethanolic extracts of M. americana and T. cymosa seeds were subjected to open column chromatographic fractionation, leading to the identification of four compounds: two coumarins, derived from M. americana; and lupeol acetate and voacangine derived from T. cymosa.. The cytotoxicity of each compound was subsequently assessed by the MTT method (at concentrations from 400 to 6.25 μg/mL). Pre- and post-treatment antiviral assays were performed at non-toxic concentrations; the resulting DENV inhibition was evaluated by Real-Time PCR, and the CHIKV inhibition was tested by the plating method. The results were analyzed by means of statistical analysis. The compounds showed low toxicity at concentrations ≤ 200 μg/mL. The compounds coumarin A and coumarin B, which are derived from the M. americana plant, significantly inhibited infection with both viruses during the implementation of the two experimental strategies employed here (post-treatment with inhibition percentages greater than 50%, p treatment with percentages of inhibition greater than 40%, p treatment strategy (at inhibition percentages greater than 70%, p treating Dengue and Chikungunya fever. Additionally, lupeol acetate and voacangine efficiently inhibit infection with DENV, also turning them into promising antivirals for Dengue fever.

  11. Identification and characterization of a virus-specific continuous B-cell epitope on the PrM/M protein of Japanese Encephalitis Virus: potential application in the detection of antibodies to distinguish Japanese Encephalitis Virus infection from West Nile Virus and Dengue Virus infections

    OpenAIRE

    Hua, Rong-Hong; Chen, Na-Sha; Qin, Cheng-Feng; Deng, Yong-Qiang; Ge, Jin-Ying; Wang, Xi-Jun; Qiao, Zu-Jian; Chen, Wei-Ye; Wen, Zhi-Yuan; Liu, Wen-Xin; Hu, Sen; Bu, Zhi-Gao

    2010-01-01

    Abstract Background Differential diagnose of Japanese encephalitis virus (JEV) infection from other flavivirus especially West Nile virus (WNV) and Dengue virus (DV) infection was greatly hindered for the serological cross-reactive. Virus specific epitopes could benefit for developing JEV specific antibodies detection methods. To identify the JEV specific epitopes, we fully mapped and characterized the continuous B-cell epitope of the PrM/M protein of JEV. Results To map the epitopes on the P...

  12. Bilateral rectus sheath haematoma complicating dengue virus infection in a patient on warfarin for mechanical aortic valve replacement: a case report.

    Science.gov (United States)

    Rosa, Chamith Thushanga; Navinan, Mitrakrishnan Rayno; Samarawickrama, Sincy; Hamza, Himam; Gunarathne, Maheshika; Arulanantham, Arulprashanth; Subba, Neeha; Samarasiri, Udari; Mathias, Thushara; Kulatunga, Aruna

    2017-01-07

    The management of Dengue virus infection can be challenging. Varied presentations and numerous complications intrinsic to dengue by itself increase the complexity of treatment and potential mortality. When burdened with the presence of additional comorbidities and the need to continue compulsory medications, clear stepwise definitive guidance is lacking and patients tend to have more complex complications and outcomes calling to question the clinical decisions that may have been taken. The use and continuation of warfarin in dengue virus infection is one such example. We report a 65 year old South Asian female who presented with dengue fever. She had a history bronchial asthma, a prior abdominal surgery, and was on warfarin and maintained a therapeutically appropriate internationalized normalized ratio for a mechanical aortic valve replacement. Though preemptive decision to stop warfarin was taken with decreasing platelet counts, her clinical course was complicated with the development of bilateral rectus sheath haematoma's requiring resuscitation with blood transfusions. Though management of dengue viral fever has seen drastic evolution with recent updated guidance, clinical scenarios seen in the course of the illness still pose challenges to the managing physician. The need to continue obligatory anticoagulation which may seem counterintuitive during a complex disease such as dengue virus infection must be considered after understanding the potential risks versus that of its benefits. Though case by case decisions maybe warranted, a clear protocol would be very helpful in making clinical decisions, as the correct preemptive decision may potentially avert catastrophic and unpredictable bleeding events.

  13. Vectorial capacity of Aedes aegypti for dengue virus type 2 is reduced with co-infection of Metarhizium anisopliae.

    Science.gov (United States)

    Garza-Hernández, Javier A; Rodríguez-Pérez, Mario A; Salazar, Ma Isabel; Russell, Tanya L; Adeleke, Monsuru A; de Luna-Santillana, Erik de J; Reyes-Villanueva, Filiberto

    2013-01-01

    Aedes aegypti, is the major dengue vector and a worldwide public health threat combated basically by chemical insecticides. In this study, the vectorial competence of Ae. aegypti co-infected with a mildly virulent Metarhizium anisopliae and fed with blood infected with the DENV-2 virus, was examined. The study encompassed three bioassays (B). In B1 the median lethal time (LT50) of Ae. aegypti exposed to M. anisopliae was determined in four treatments: co-infected (CI), single-fungus infection (SF), single-virus infection (SV) and control (C). In B2, the mortality and viral infection rate in midgut and in head were registered in fifty females of CI and in SV. In B3, the same treatments as in B1 but with females separated individually were tested to evaluate the effect on fecundity and gonotrophic cycle length. Survival in CI and SF females was 70% shorter than the one of those in SV and control. Overall viral infection rate in CI and SV were 76 and 84% but the mortality at day six post-infection was 78% (54% infected) and 6% respectively. Survivors with virus in head at day seven post-infection were 12 and 64% in both CI and SV mosquitoes. Fecundity and gonotrophic cycle length were reduced in 52 and 40% in CI compared to the ones in control. Fungus-induced mortality for the CI group was 78%. Of the survivors, 12% (6/50) could potentially transmit DENV-2, as opposed to 64% (32/50) of the SV group, meaning a 5-fold reduction in the number of infective mosquitoes. This is the first report on a fungus that reduces the vectorial capacity of Ae. aegypti infected with the DENV-2 virus.

  14. Dengue Virus and Autophagy

    Directory of Open Access Journals (Sweden)

    Nicholas S. Heaton

    2011-08-01

    Full Text Available Several independent groups have published that autophagy is required for optimal RNA replication of dengue virus (DENV. Initially, it was postulated that autophagosomes might play a structural role in replication complex formation. However, cryo-EM tomography of DENV replication complexes showed that DENV replicates on endoplasmic reticulum (ER cisternae invaginations and not on classical autophagosomes. Recently, it was reported that autophagy plays an indirect role in DENV replication by modulating cellular lipid metabolism. DENV-induced autophagosomes deplete cellular triglycerides that are stored in lipid droplets, leading to increased β-oxidation and energy production. This is the first example of a virus triggering autophagy to modulate cellular physiology. In this review, we summarize these data and discuss new questions and implications for autophagy during DENV replication.

  15. A model of immunomodulatory for dengue infection mm

    Science.gov (United States)

    Zulfa, Annisa; Handayani, Dewi; Nuraini, Nuning

    2018-03-01

    An immunomodulatory model for dengue infection is constructed in this paper. This study focuses on T-cell compartments and B cells that are immune cells involved in the dengue infection process. Dengue virus-infected monocyte cells release interferons to signal T-cells to activate B-cells and produce antibodies. Immunomodulator acts as a treatment control and aims to increase the numbers of antibodies so it is expected to reduce the number of infected monocyte cells by dengue virus. Numerical simulation shows that the greater the rate of f (t) the immune cells will be stimulated to suppress the number of infected cells.

  16. Dengue Virus Genome Uncoating Requires Ubiquitination

    Directory of Open Access Journals (Sweden)

    Laura A. Byk

    2016-06-01

    Full Text Available The process of genome release or uncoating after viral entry is one of the least-studied steps in the flavivirus life cycle. Flaviviruses are mainly arthropod-borne viruses, including emerging and reemerging pathogens such as dengue, Zika, and West Nile viruses. Currently, dengue virus is one of the most significant human viral pathogens transmitted by mosquitoes and is responsible for about 390 million infections every year around the world. Here, we examined for the first time molecular aspects of dengue virus genome uncoating. We followed the fate of the capsid protein and RNA genome early during infection and found that capsid is degraded after viral internalization by the host ubiquitin-proteasome system. However, proteasome activity and capsid degradation were not necessary to free the genome for initial viral translation. Unexpectedly, genome uncoating was blocked by inhibiting ubiquitination. Using different assays to bypass entry and evaluate the first rounds of viral translation, a narrow window of time during infection that requires ubiquitination but not proteasome activity was identified. In this regard, ubiquitin E1-activating enzyme inhibition was sufficient to stabilize the incoming viral genome in the cytoplasm of infected cells, causing its retention in either endosomes or nucleocapsids. Our data support a model in which dengue virus genome uncoating requires a nondegradative ubiquitination step, providing new insights into this crucial but understudied viral process.

  17. Immature dengue virus: a veiled pathogen?

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    Izabela A Rodenhuis-Zybert

    2010-01-01

    Full Text Available Cells infected with dengue virus release a high proportion of immature prM-containing virions. In accordance, substantial levels of prM antibodies are found in sera of infected humans. Furthermore, it has been recently described that the rates of prM antibody responses are significantly higher in patients with secondary infection compared to those with primary infection. This suggests that immature dengue virus may play a role in disease pathogenesis. Interestingly, however, numerous functional studies have revealed that immature particles lack the ability to infect cells. In this report, we show that fully immature dengue particles become highly infectious upon interaction with prM antibodies. We demonstrate that prM antibodies facilitate efficient binding and cell entry of immature particles into Fc-receptor-expressing cells. In addition, enzymatic activity of furin is critical to render the internalized immature virus infectious. Together, these data suggest that during a secondary infection or primary infection of infants born to dengue-immune mothers, immature particles have the potential to be highly infectious and hence may contribute to the development of severe disease.

  18. Aedes mosquito salivary immune peptides: boost or block dengue viral infections

    Directory of Open Access Journals (Sweden)

    Natthanej Luplertlop

    2014-02-01

    Full Text Available Dengue virus, one of the most important arthropod-borne viruses, infected to human can severely cause dengue hemorrhagic fever and dengue shock syndrome. There are expected about 50 million dengue infections and 500 000 individuals are hospitalized with dengue hemorrhagic fever, mainly in Southeast Asia, Pacific, and in Americas reported each year. The rapid expansion of global dengue is one of a major public health challenge, together with not yet successful solutions of dengue epidemic control strategies. Thus, these dynamic dengue viral infections exhibited high demographic, societal, and public health infrastructure impacts on human. This review aimed to highlight the current understanding of dengue mosquito immune responses and role of mosquito salivary glands on dengue infection. These information may provide a valuable knowledge of disease pathogenesis, especially in mosquito vector and dengue virus interaction, which may help to control and prevent dengue distribution.

  19. Elevated levels of total and dengue virus-specific immunoglobulin E in patients with varying disease severity

    NARCIS (Netherlands)

    Koraka, Penelopie; Murgue, Bernadette; Deparis, Xavier; Setiati, Tatty E.; Suharti, Catarina; van Gorp, Eric C. M.; Hack, C. E.; Osterhaus, Albert D. M. E.; Groen, Jan

    2003-01-01

    The kinetics of total and dengue virus-specific immunoglobulin E (IgE) were studied in serial serum samples obtained from 168 patients, 41 of whom suffered from primary dengue virus infection and 127 suffered from secondary dengue virus infection. Seventy-one patients were classified as dengue

  20. Elevated levels of total and dengue virus-specific immunoglobulin E in patients with varying disease severity.

    NARCIS (Netherlands)

    Koraka, P.; Murgue, B.; Deparis, X.; Setiati, T.E.; Suharti, C.; Gorp, E. van; Hack, C.E.; Osterhaus, A.D.; Groen, J.

    2003-01-01

    The kinetics of total and dengue virus-specific immunoglobulin E (IgE) were studied in serial serum samples obtained from 168 patients, 41 of whom suffered from primary dengue virus infection and 127 suffered from secondary dengue virus infection. Seventy-one patients were classified as dengue

  1. Gefitinib and pyrrolidine dithiocarbamate decrease viral replication and cytokine production in dengue virus infected human monocyte cultures.

    Science.gov (United States)

    Duran, Anyelo; Valero, Nereida; Mosquera, Jesús; Fuenmayor, Edgard; Alvarez-Mon, Melchor

    2017-12-15

    The epidermal growth factor receptor (EGFR) and nucleotide-binding and oligomerization-domain containing 2 (NOD2) are important in cancer and in microbial recognition, respectively. These molecules trigger intracellular signaling pathways inducing the expression of inflammatory genes by NF-kB translocation. Gefitinib (GBTC) and pyrrolidine dithiocarbamate (PDTC) are capable of inhibiting EGFR/NOD2 and NF-kB, respectively. In earlier stages of dengue virus (DENV) infection, monocytes are capable of sustaining viral replication and increasing cytokine production, suggesting that monocyte/macrophages play an important role in early DENV replication. GBTC and PDTC have not been used to modify the pathogenesis of DENV in infected cells. This study was aimed to determine the effect of GBTC and PDTC on viral replication and cytokine production in DENV serotype 2 (DENV2)-infected human monocyte cultures. GBTC and PDTC were used to inhibit EGFR/NOD2 and NF-kB, respectively. Cytokine production was measured by ELISA and viral replication by plaque forming unit assay. Increased DENV2 replication and anti-viral cytokine production (IFN-α/β, TNF-α, IL-12 and IL-18) in infected cultures were found. These parameters were decreased after EGFR/NOD2 or NF-kB inhibitions. The inhibitory effects of GBTC and PDTC on viral replication and cytokine production can be beneficial in the treatment of patients infected by dengue and suggest a possible role of EGFR/NOD2 receptors and NF-kB in dengue pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Peptides as Therapeutic Agents for Dengue Virus.

    Science.gov (United States)

    Chew, Miaw-Fang; Poh, Keat-Seong; Poh, Chit-Laa

    2017-01-01

    Dengue is an important global threat caused by dengue virus (DENV) that records an estimated 390 million infections annually. Despite the availability of CYD-TDV as a commercial vaccine, its long-term efficacy against all four dengue virus serotypes remains unsatisfactory. There is therefore an urgent need for the development of antiviral drugs for the treatment of dengue. Peptide was once a neglected choice of medical treatment but it has lately regained interest from the pharmaceutical industry following pioneering advancements in technology. In this review, the design of peptide drugs, antiviral activities and mechanisms of peptides and peptidomimetics (modified peptides) action against dengue virus are discussed. The development of peptides as inhibitors for viral entry, replication and translation is also described, with a focus on the three main targets, namely, the host cell receptors, viral structural proteins and viral non-structural proteins. The antiviral peptides designed based on these approaches may lead to the discovery of novel anti-DENV therapeutics that can treat dengue patients.

  3. Phylogenetic analysis of Dengue virus 1 isolated from South Minas Gerais, Brazil

    OpenAIRE

    Drumond, Betania Paiva; Fagundes, Luiz Gustavo da Silva; Rocha, Raissa Prado; Fumagalli, Marcilio Jorge; Araki, Carlos Shigueru; Colombo, Tatiana Elisa; Nogueira, Mauricio Lacerda; Castilho, Thiago Elias; Silveira, Nelson José Freitas da; Malaquias, Luiz Cosme Cotta; Coelho, Luiz Felipe Leomil

    2016-01-01

    Abstract Dengue is a major worldwide public health problem, especially in the tropical and subtropical regions of the world. Primary infection with a single Dengue virus serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients who experience secondary infection with a different serotype can progress to a more severe form of the disease, called dengue hemorrhagic fever. The four Dengue virus serotypes (1–4) are antigenically and genetically...

  4. Changing haematological parameters in dengue viral infections

    International Nuclear Information System (INIS)

    Jamil, T.; Mehmood, K.; Mujtaba, G.; Choudhry, N.

    2012-01-01

    Background: Dengue Fever is the most common arboviral disease in the world, and presents cyclically in tropical and subtropical regions of the world. The four serotypes of dengue virus, 1, 2, 3, and 4, form an antigenic subgroup of the flaviviruses (Group B arboviruses). Transmission to humans of any of these serotypes initiates a spectrum of host responses, from in apparent to severe and sometimes lethal infections. Complete Blood count (CBC) is an important part of the diagnostic workup of patients. Comparison of various finding in CBC including peripheral smear can help the physician in better management of the patient. Material and Methods: This cross sectional study was carried out on a series of suspected patients of Dengue viral infection reporting in Ittefaq Hospital (Trust). All were investigated for serological markers of acute infection. Results Out of 341 acute cases 166 (48.7%) were confirmed by IgM against Dengue virus. IgG anti-dengue was used on 200 suspected re-infected patients. Seventy-one (39.5%) were positive and 118 (59%) were negative. Among 245 confirmed dengue fever patients 43 (17.6%) were considered having dengue hemorrhagic fever on the basis of lab and clinical findings. Raised haematocrit, Leukopenia with relative Lymphocytosis and presence atypical lymphocytes along with plasmacytoid cells was consistent finding at presentation in both the patterns of disease, i.e., Dengue Haemorrhagic fever (DHF) and Dengue fever (DF). Conclusion: Changes in relative percentage of cells appear with improvement in the symptoms and recovery from the disease. These findings indicate that in the course of the disease, there are major shifts within cellular component of blood. (author)

  5. Dengue fever with hepatitis E and hepatitis A infection.

    Science.gov (United States)

    Yakoob, Javed; Jafri, Wasim; Siddiqui, Shaheer; Riaz, Mehmood

    2009-03-01

    Infection with dengue viruses produces a spectrum of clinical illness ranging from a nonspecific viral syndrome to severe and fatal haemorrhagic disease. Important risk factors include the strain and serotype of the infecting virus, as well as the age, immune status, and genetic predisposition of the patient. The teaching point in this case study was Dengue fever which occurred concomitantly with Hepatitis A and Hepatitis E virus infection.

  6. Activation of TLR2 and TLR6 by Dengue NS1 Protein and Its Implications in the Immunopathogenesis of Dengue Virus Infection.

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    Jincheng Chen

    2015-07-01

    Full Text Available Dengue virus (DV infection is the most prevalent mosquito-borne viral disease and its manifestation has been shown to be contributed in part by the host immune responses. In this study, pathogen recognition receptors, Toll-like receptor (TLR 2 and TLR6 were found to be up-regulated in DV-infected human PBMC using immunofluorescence staining, flow cytometry and Western blot analyses. Using ELISA, IL-6 and TNF-α, cytokines downstream of TLR2 and TLR6 signaling pathways were also found to be up-regulated in DV-infected PBMC. IL-6 and TNF-α production by PBMC were reduced when TLR2 and TLR6 were blocked using TLR2 and TLR6 neutralizing antibodies during DV infection. These results suggested that signaling pathways of TLR2 and TLR6 were activated during DV infection and its activation contributed to IL-6 and TNF-α production. DV NS1 protein was found to significantly increase the production of IL-6 and TNF-α when added to PBMC. The amount of IL-6 and TNF-α stimulated by DV NS1 protein was reduced when TLR2 and TLR6 were blocked, suggesting that DV NS1 protein is the viral protein responsible for the activation of TLR2 and TLR6 during DV infection. Secreted alkaline phosphatase (SEAP reporter assay was used to further confirm activation of TLR2 and TLR6 by DV NS1 protein. In addition, DV-infected and DV NS1 protein-treated TLR6-/- mice have higher survivability compared to DV-infected and DV NS1 protein-treated wild-type mice. Hence, activation of TLR6 via DV NS1 protein could potentially play an important role in the immunopathogenesis of DV infection.

  7. Dengue virus infection among long-term travelers from the Netherlands: A prospective study, 2008-2011.

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    Femke W Overbosch

    Full Text Available Dengue is increasing rapidly in endemic regions. Data on incidence among travelers to these areas are limited. Five prospective studies have been performed thus far, mainly among short-term travelers.To obtain the attack and incidence rate (AR, IR of dengue virus (DENV infection among long-term travelers and identify associated risk factors.A prospective study was performed among long-term travelers (12-52 weeks attending the Public Health Service in Amsterdam. Clients planning to travel to (subtropical countries were invited to participate. Participants kept a travel diary, recording itinerary, symptoms, and physician visits. Pre- and post-travel blood samples were serologically tested for the presence of Anti-DENV IgG antibodies. Seroconversion was considered suggestive of a primary DENV infection. Anti-DENV IgG present in both corresponding samples in combination with a post-/pre-travel ratio of ≥4:1 was suggestive of a secondary infection. Risk factors for a DENV infection were studied using poisson regression.In total, 600 participants were included; median age was 25 years (IQR: 23-29, 35.5% were male, and median travel duration was 20 weeks (IQR: 15-25. In 39 of 600 participants (AR: 6.5%; 95% CI 4.5-8.5% anti-DENV IgG test results were suggestive of a recent infection, yielding an IR of 13.9 per 1,000 person-months traveling (95%CI: 9.9-19.1. No secondary infections were found. IR for Asia, Africa, and America were comparable and 13.5, 15.8, and 13.6 per 1,000 person-months respectively. Of participants with a recent DENV infection, 51% did not report dengue-like illness (DLI or fever, but 10% were hospitalized. In multivariable analysis, travelers who seroconverted were significantly more likely to be vaccinated with ≥2 flavivirus vaccines for the current trip or to have reported DLI in >1 consecutive weeks.Long-term travelers are at substantial risk of DENV infection. Half of those with a DENV infection reported no symptoms, but 10

  8. Aedes albopictus (Skuse, 1894) infected with the American-Asian genotype of dengue type 2 virus in Medellín suggests its possible role as vector of dengue fever in Colombia.

    Science.gov (United States)

    Gómez-Palacio, Andrés; Suaza-Vasco, Juan; Castaño, Sandra; Triana, Omar; Uribe, Sandra

    2017-03-29

    Aedes aegypti and Ae. albopictus are recognized vectors of dengue, yellow fever, chikungunya and Zika arboviruses in several countries worldwide. In Colombia, Ae. albopictus geographical distribution has increased to include highly populated cities such as Cali and Medellín. Although this species has been frequently found in urban and semi-urban zones in the country, its role as vector of the dengue fever is poorly known. To identify the presence of Ae. albopictus specimens naturally infected with dengue virus collected in Medellín. Insects were collected in the Universidad Nacional de Colombia campus in Medellín. Individuals were classified as Ae. albopictus and confirmed by DNA barcode region analysis. Mosquitoes were processed for dengue virus identification, and a fragment of the NS3 gen was sequenced and compared with DENV-2 genotypes reported in the literature. Sequence analysis of COI indicated Ae. albopictus individuals were similar to those recently reported in Colombia, and genetically close to those from other regions worldwide. Among the pools tested one was positive for DENV-2, and the NS3 analysis indicated it belonged to the Asian-American clade. We report the presence Ae. albopictus naturally infected with the Asian-American genotype of DENV-2 in Colombia. The presence of Ae. albopictus specimens carrying the most common genotype infecting humans in a highly populated city such as Medellín indicates its potential role as dengue vector in Colombia and highlights the relevance of including it in current vector surveillance strategies.

  9. AEGY-28 Cell Line of Aedes aegypti (Diptera Culicidae is Infection Refractory to Dengue 2 and Yellow Fever Virus

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    Nadia Y. Castañeda

    2007-07-01

    Full Text Available Mosquito cell derived cultures are useful tools for arbovirus isolation, identification or characterization. For studying dengue (DENV and yellow fever viruses (YFV Aedes albopictus C6/36 or Aedes pseudoscutellaris AP-61 cell lines, are normally used. The Aedes aegypti AEGY-28 cell line was obtained from embryonic tissues and characterized previously by one of us. In order to evaluate its susceptibility to two Flavivirus, AEGY- 28 cells were inoculated with different multiplicity of infection (MOI with type 2 DENV (COL-789, MOI: 1 and 5 and YFV clinical isolates (V-341, MOI 0,02 then processed at different times post infection (p.i.. Immunostai ning and fluorometric cell-ELISA were carried out to identify and quantify viral antigens. C6/36 and Vero cells were used as positive controls. Unexpectedly, immunoreactivity was not found in inoculated AEGY-28 cells, even in higher MOI or late times p.i., therefore antigen quantification using fluorometric cell-ELISA were not  plausible. Reverse transcriptase PCR with specific primers did not detect viral RNA in AEGY-28 inoculated cells. We can conclude that Aedes aegypti AEGY-28 cell line is not susceptible to dengue and yellow fever Flavivirus, a finding possibly related with the lacking of specific molecules at the plasma membrane or absence of cell machinery necessary for viral replication.

  10. Prolonged viremia in dengue virus infection in hematopoietic stem cell transplant recipients and patients with hematological malignancies.

    Science.gov (United States)

    de Souza Pereira, Bárbara Brito; Darrigo Junior, Luiz Guilherme; de Mello Costa, Thalita Cristina; Felix, Alvina Clara; Simoes, Belinda P; Stracieri, Ana Beatriz; da Silva, Paula Moreira; Mauad, Marcos; Machado, Clarisse M

    2017-08-01

    Fever, skin rash, headache, and thrombocytopenia are considered hallmarks of dengue infection. However, these symptoms are frequently observed in infectious and non-infectious complications of hematopoietic stem cell transplant recipients and oncohematological patients. Thus, laboratory confirmation of dengue is relevant for prompt intervention and proper management of dengue in endemic and non-endemic regions. Because no prospective study of dengue has been conducted in these populations, the actual morbidity and mortality of dengue is unknown. In the present series, we describe five cases of dengue in patients living in endemic areas, emphasizing the prolonged course of the disease and the occurrence of prolonged viremia. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Dengue Virus Glycosylation: What Do We Know?

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    Sally S. L. Yap

    2017-07-01

    Full Text Available In many infectious diseases caused by either viruses or bacteria, pathogen glycoproteins play important roles during the infection cycle, ranging from entry to successful intracellular replication and host immune evasion. Dengue is no exception. Dengue virus glycoproteins, envelope protein (E and non-structural protein 1 (NS1 are two popular sub-unit vaccine candidates. E protein on the virion surface is the major target of neutralizing antibodies. NS1 which is secreted during DENV infection has been shown to induce a variety of host responses through its binding to several host factors. However, despite their critical role in disease and protection, the glycosylated variants of these two proteins and their biological importance have remained understudied. In this review, we seek to provide a comprehensive summary of the current knowledge on protein glycosylation in DENV, and its role in virus biogenesis, host cell receptor interaction and disease pathogenesis.

  12. The influence of dengue virus serotype-2 infection on Aedes aegypti (Diptera: Culicidae motivation and avidity to blood feed.

    Directory of Open Access Journals (Sweden)

    Rafael Maciel-de-Freitas

    Full Text Available BACKGROUND: Dengue virus (DENV is transmitted by Aedes aegypti, a species that lives in close association with human dwellings. The behavior of DENV-infected mosquitoes needs further investigation, especially regarding the potential influence of DENV on mosquito biting motivation and avidity. METHODOLOGY/PRINCIPAL FINDINGS: We orally challenged 4-5 day-old Ae. aegypti females with a low passage DENV serotype -2 (DENV-2 to test whether the virus influences motivation to feed (the likelihood that a mosquito obtains a blood-meal and the size of its blood meal and avidity (the likelihood to re-feed after an interrupted first blood-meal. To assay motivation, we offered mosquitoes an anesthetized mouse for 2, 3, 4 or 5 minutes 7 or 14 days after the initial blood meals and measured the time they started feeding. 60.5% of the unexposed mosquitoes fed on the mouse, but only 40.5% of the positive ones did. Exposed but negative mosquitoes behaved similarly to unexposed ones (55.0% feeding. Thus DENV-2 infection decreased the mosquitoes' motivation to feed. To assay avidity, we offered the same mosquitoes a mouse two hours after the first round of feeding, and we measured the time at which they started probing. The exposed (positive or negative mosquitoes were more likely to re-feed than the unexposed ones and, in particular, the size of the previous blood-meal that kept mosquitoes from re-feeding was larger in the exposed than in the unexposed mosquitoes. Thus, DENV-2 infection increased mosquito avidity. CONCLUSIONS/SIGNIFICANCE: DENV-2 significantly decreased the mosquitoes' motivation to feed, but increased their avidity (even after taking account the amount of blood previously imbibed. As these are important components of transmission, we expect that the changes of the blood-feeding behaviour impact the vectorial capacity Ae. aegypti for dengue.

  13. The influence of dengue virus serotype-2 infection on Aedes aegypti (Diptera: Culicidae) motivation and avidity to blood feed.

    Science.gov (United States)

    Maciel-de-Freitas, Rafael; Sylvestre, Gabriel; Gandini, Mariana; Koella, Jacob C

    2013-01-01

    Dengue virus (DENV) is transmitted by Aedes aegypti, a species that lives in close association with human dwellings. The behavior of DENV-infected mosquitoes needs further investigation, especially regarding the potential influence of DENV on mosquito biting motivation and avidity. We orally challenged 4-5 day-old Ae. aegypti females with a low passage DENV serotype -2 (DENV-2) to test whether the virus influences motivation to feed (the likelihood that a mosquito obtains a blood-meal and the size of its blood meal) and avidity (the likelihood to re-feed after an interrupted first blood-meal). To assay motivation, we offered mosquitoes an anesthetized mouse for 2, 3, 4 or 5 minutes 7 or 14 days after the initial blood meals and measured the time they started feeding. 60.5% of the unexposed mosquitoes fed on the mouse, but only 40.5% of the positive ones did. Exposed but negative mosquitoes behaved similarly to unexposed ones (55.0% feeding). Thus DENV-2 infection decreased the mosquitoes' motivation to feed. To assay avidity, we offered the same mosquitoes a mouse two hours after the first round of feeding, and we measured the time at which they started probing. The exposed (positive or negative) mosquitoes were more likely to re-feed than the unexposed ones and, in particular, the size of the previous blood-meal that kept mosquitoes from re-feeding was larger in the exposed than in the unexposed mosquitoes. Thus, DENV-2 infection increased mosquito avidity. DENV-2 significantly decreased the mosquitoes' motivation to feed, but increased their avidity (even after taking account the amount of blood previously imbibed). As these are important components of transmission, we expect that the changes of the blood-feeding behaviour impact the vectorial capacity Ae. aegypti for dengue.

  14. Mathematical analysis of dengue virus antibody dynamics

    Science.gov (United States)

    Perera, Sulanie; Perera, SSN

    2018-03-01

    Dengue is a mosquito borne viral disease causing over 390 million infections worldwide per annum. Even though information on how infection is controlled and eradicated from the body is lacking, antibodies are thought to play a major role in clearing the virus. In this paper, a non-linear conceptual dynamical model with humoral immune response and absorption effect has been proposed for primary dengue infection. We have included the absorption of pathogens into uninfected cells since this effect causes the virus density in the blood to decrease. The time delay that arises in the production of antibodies was accounted and is introduced through a continuous function. The basic reproduction number R0 is computed and a detailed stability analysis is done. Three equilibrium states, namely the infection free equilibrium, no immune equilibrium and the endemic equilibrium were identified and the existence and the stability conditions of these steady states were obtained. Numerical simulations proved the results that were obtained. By establishing the characteristic equation of the model at infection free equilibrium, it was observed that the infection free equilibrium is locally asymptotically stable if R0 1. Stability regions are identified for infection free equilibrium state with respect to the external variables and it is observed as the virus burst rate increases, the stability regions would decrease. These results implied that for higher virus burst rates, other conditions in the body must be strong enough to eliminate the disease completely from the host. The effect of time delay of antibody production on virus dynamics is discussed. It was seen that as the time delay in production of antibodies increases, the time for viral decline also increased. Also it was observed that the virus count goes to negligible levels within 7 - 14 days after the onset of symptoms as seen in dengue infections.

  15. Dengue Fever/Dengue Haemorrhagic Fever : Case Management

    OpenAIRE

    Nimmannitya, Suchitra

    1995-01-01

    Dengue infections caused by the four antigenically distinct dengue virus serotypes (dengue virus 1, dengue virus 2, dengue virus 3, dengue virus 4) of the family Flavivindae, are the most important arbovirus disease in man, both in terms of morbidity and mortality. The infection is transmitted from man to man by Aedes mosquitoes. Since 1956, dengue virus infection has resulted in more than 3 million hospital admissions and more than 50,000 deaths in Southeast Asia, Western Pacific countries, ...

  16. A novel mosquito ubiquitin targets viral envelope protein for degradation and reduces virion production during dengue virus infection.

    Science.gov (United States)

    Troupin, Andrea; Londono-Renteria, Berlin; Conway, Michael J; Cloherty, Erin; Jameson, Samuel; Higgs, Stephen; Vanlandingham, Dana L; Fikrig, Erol; Colpitts, Tonya M

    2016-09-01

    Dengue virus (DENV) is a mosquito-borne flavivirus that causes significant human disease and mortality in the tropics and subtropics. By examining the effects of virus infection on gene expression, and interactions between virus and vector, new targets for prevention of infection and novel treatments may be identified in mosquitoes. We previously performed a microarray analysis of the Aedes aegypti transcriptome during infection with DENV and found that mosquito ubiquitin protein Ub3881 (AAEL003881) was specifically and highly down-regulated. Ubiquitin proteins have multiple functions in insects, including marking proteins for proteasomal degradation, regulating apoptosis and mediating innate immune signaling. We used qRT-PCR to quantify gene expression and infection, and RNAi to reduce Ub3881 expression. Mosquitoes were infected with DENV through blood feeding. We transfected DENV protein expression constructs to examine the effect of Ub3881 on protein degradation. We used site-directed mutagenesis and transfection to determine what amino acids are involved in Ub3881-mediated protein degradation. Immunofluorescence, Co-immunoprecipitation and Western blotting were used to examine protein interactions and co-localization. The overexpression of Ub3881, but not related ubiquitin proteins, decreased DENV infection in mosquito cells and live Ae. aegypti. The Ub3881 protein was demonstrated to be involved in DENV envelope protein degradation and reduce the number of infectious virions released. We conclude that Ub3881 has several antiviral functions in the mosquito, including specific viral protein degradation. Our data highlights Ub3881 as a target for future DENV prevention strategies in the mosquito transmission vector. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Combination of α-glucosidase inhibitor and ribavirin for the treatment of dengue virus infection in vitro and in vivo.

    Science.gov (United States)

    Chang, Jinhong; Schul, Wouter; Butters, Terry D; Yip, Andy; Liu, Boping; Goh, Anne; Lakshminarayana, Suresh B; Alonzi, Dominic; Reinkensmeier, Gabriele; Pan, Xiaoben; Qu, Xiaowang; Weidner, Jessica M; Wang, Lijuan; Yu, Wenquan; Borune, Nigel; Kinch, Mark A; Rayahin, Jamie E; Moriarty, Robert; Xu, Xiaodong; Shi, Pei-Yong; Guo, Ju-Tao; Block, Timothy M

    2011-01-01

    Cellular α-glucosidases I and II are enzymes that sequentially trim the three terminal glucoses in the N-linked oligosaccharides of viral envelope glycoproteins. This process is essential for the proper folding of viral glycoproteins and subsequent assembly of many enveloped viruses, including dengue virus (DENV). Imino sugars are substrate mimics of α-glucosidases I and II. In this report, we show that two oxygenated alkyl imino sugar derivatives, CM-9-78 and CM-10-18, are potent inhibitors of both α-glucosidases I and II in vitro and in treated animals, and efficiently inhibit DENV infection of cultured human cells. Pharmacokinetic studies reveal that both compounds are well tolerated at doses up to 100mg/kg in rats and have favorable pharmacokinetic properties and bioavailability in mice. Moreover, we showed that oral administration of either CM-9-78 or CM-10-18 reduces the peak viremia of DENV in mice. Interestingly, while treatment of DENV infected mice with ribavirin alone did not reduce the viremia, combination therapy of ribavirin with sub-effective dose of CM-10-18 demonstrated a significantly enhanced antiviral activity, as indicated by a profound reduction of the viremia. Our findings thus suggest that combination therapy of two broad-spectrum antiviral agents may provide a practically useful approach for the treatment of DENV infection. Copyright © 2010 Elsevier B.V. All rights reserved.

  18. Combination of alpha-glucosidase inhibitor and ribavirin for the treatment of Dengue virus infection in vitro and in vivo

    Science.gov (United States)

    Chang, Jinhong; Schul, Wouter; Butters, Terry D.; Yip, Andy; Liu, Boping; Goh, Anne; Lakshminarayana, Suresh B.; Alonzi, Dominic; Reinkensmeier, Gabriele; Pan, Xiaoben; Qu, Xiaowang; Weidner, Jessica M.; Wang, Lijuan; Yu, Wenquan; Borune, Nigel; Kinch, Mark A.; Rayahin, Jamie E.; Moriarty, Robert; Xu, Xiaodong; Shi, Pei-Yong; Guo, Ju-Tao; Block, Timothy M.

    2010-01-01

    Cellular α-glucosidases I and II are enzymes that sequentially trim the three terminal glucoses in the N-linked oligosaccharides of viral envelope glycoproteins. This process is essential for the proper folding of viral glycoproteins and subsequent assembly of many enveloped viruses, including dengue virus (DENV). Imino sugars are substrate mimics of α-glucosidases I and II. In this report, we show that two oxygenated alkyl imino sugar derivatives, CM-9-78 and CM-10-18, are potent inhibitors of both α-glucosidases I and II in vitro and in treated animals, and efficiently inhibit DENV infection of cultured human cells. Pharmacokinetic studies reveal that both compounds are well tolerated at doses up to 100mg/kg in rats and have favorable pharmacokinetic properties and bioavailability in mice. Moreover, we showed that oral administration of either CM-9-78 or CM-10-18 reduces the peak viremia of DENV in mice. Interestingly, while treatment of DENV infected mice with ribavirin alone did not reduce the viremia, combination therapy of ribavirin with sub-effective dose of CM-10-18 demonstrated a significantly enhanced antiviral activity, as indicated by a profound reduction of the viremia. Our findings thus suggest that combination therapy of two broad-spectrum antiviral agents may provide a practically useful approach for the treatment of DENV infection. PMID:21073903

  19. Dengue virus detection by using reverse transcription-polymerase chain reaction in saliva and progeny of experimentally infected Aedes albopictus from Brazil

    Directory of Open Access Journals (Sweden)

    Márcia Gonçalves de Castro

    2004-12-01

    Full Text Available Oral susceptibility and vertical transmission of dengue virus type 2 (DENV-2 in an Aedes albopictus sample from Rio de Janeiro was estimated. The infection (36.7% and transmission (83.3% rates for Ae. albopictus were higher than those of an Ae. aegypti colony used as control, 32.8 and 60%, respectively. Fourth instar larvae and females descendants of 48.5 and 39.1% of experimentally infected Ae. albopictus showed to harbor the virus. The oral susceptibility and the high capacity to assure vertical transmission exhibited by Ae. albopictus from Brazil reinforce that this species may play a role in the maintenance of the virus in nature and be a threat for dengue control in the country.

  20. Distinct activation phenotype of a highly conserved novel HLA-B57-restricted epitope during dengue virus infection.

    Science.gov (United States)

    Townsley, Elizabeth; Woda, Marcia; Thomas, Stephen J; Kalayanarooj, Siripen; Gibbons, Robert V; Nisalak, Ananda; Srikiatkhachorn, Anon; Green, Sharone; Stephens, Henry A F; Rothman, Alan L; Mathew, Anuja

    2014-01-01

    Variation in the sequence of T-cell epitopes between dengue virus (DENV) serotypes is believed to alter memory T-cell responses during second heterologous infections. We identified a highly conserved, novel, HLA-B57-restricted epitope on the DENV NS1 protein. We predicted higher frequencies of B57-NS1(26-34) -specific CD8(+) T cells in peripheral blood mononuclear cells from individuals undergoing secondary rather than primary DENV infection. However, high tetramer-positive T-cell frequencies during acute infection were seen in only one of nine subjects with secondary infection. B57-NS1(26-34) -specific and other DENV epitope-specific CD8(+) T cells, as well as total CD8(+) T cells, expressed an activated phenotype (CD69(+) and/or CD38(+)) during acute infection. In contrast, expression of CD71 was largely limited to DENV epitope-specific CD8(+) T cells. In vitro stimulation of cell lines indicated that CD71 expression was differentially sensitive to stimulation by homologous and heterologous variant peptides. CD71 may represent a useful marker of antigen-specific T-cell activation. © 2013 John Wiley & Sons Ltd.

  1. Early activation of natural killer and B cells in response to primary dengue virus infection in A/J mice

    International Nuclear Information System (INIS)

    Shresta, Sujan; Kyle, Jennifer L.; Robert Beatty, P.; Harris, Eva

    2004-01-01

    Dengue virus (DEN) causes the most prevalent arthropod-borne viral illness in humans worldwide. Immune mechanisms that are involved in protection and pathogenesis of DEN infection have not been fully elucidated due largely to the lack of an adequate animal model. Therefore, as a first step, we characterized the primary immune response in immunocompetent inbred A/J mice that were infected intravenously with a non-mouse-adapted DEN type 2 (DEN2) strain. A subset (55%) of infected mice developed paralysis by 14 days post-infection (p.i.), harbored infectious DEN in the central nervous system (CNS), and had an elevated hematocrit and a decreased white blood cell (WBC) count. Immunologic studies detected (i) increased numbers of CD69 + splenic natural killer (NK) and B cells at day 3 p.i., (ii) DEN-specific IgM and IgG responses by days 3 and 7 p.i., respectively, and (iii) splenocyte production of IFNγ at day 14 p.i. We conclude that the early activities of NK cells, B cells and IgM, and later actions of IFNγ and IgG likely play a role in the defense against DEN infection

  2. [Acute renal failure after dengue virus infection: A pediatric case report].

    Science.gov (United States)

    Nicolon, C; Broustal, E

    2016-01-01

    Dengue is an emerging, rapidly expanding disease, whose clinical and biological manifestations vary. Kidney injury is not usual but can be severe, and it is most often associated with dengue hemorrhagic fever or shock. Guadeloupe, which is located in an endemic area, experienced an epidemic from 2013 to 2014. During this outbreak, a case of renal failure during dengue was observed in a 10-year-old child. No evidence of dengue hemorrhagic fever or shock syndrome was found. The clinical and biological course improved with symptomatic treatment. The association of acute renal failure with hemolytic anemia suggested a diagnosis of hemolytic uremic syndrome. However, this could not be confirmed in the absence of thrombocytopenia and cytopathologic evidence. This case illustrates the diversity of clinical presentations of dengue, and the possibility of severe renal impairment unrelated to the usual factors encountered in dengue. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  3. Characteristics and predictors for gastrointestinal hemorrhage among adult patients with dengue virus infection: Emphasizing the impact of existing comorbid disease(s.

    Directory of Open Access Journals (Sweden)

    Wen-Chi Huang

    Full Text Available Gastrointestinal (GI bleeding is a leading cause of death in dengue. This study aims to identify predictors for GI bleeding in adult dengue patients, emphasizing the impact of existing comorbid disease(s.Of 1300 adults with dengue virus infection, 175 (mean age, 56.5±13.7 years patients with GI bleeding and 1,125 (mean age, 49.2±15.6 years without GI bleeding (controls were retrospectively analyzed.Among 175 patients with GI bleeding, dengue hemorrhagic fever was found in 119 (68% patients; the median duration from onset dengue illness to GI bleeding was 5 days. Gastric ulcer, erythematous gastritis, duodenal ulcer, erosive gastritis, and hemorrhagic gastritis were found in 52.3%, 33.3%, 28.6%, 28.6%, and 14.3% of 42 patients with GI bleeding who had undergone endoscopic examination, respectively. Overall, nine of the 175 patients with GI bleeding died, giving an in-hospital mortality rate of 5.1%. Multivariate analysis showed age ≥60 years (cases vs. controls: 48% vs. 28.3% (odds ratio [OR]: 1.663, 95% confidence interval [CI]: 1.128-2.453, end stage renal disease with additional comorbidities (cases vs. controls: 1.7% vs. 0.2% (OR: 9.405, 95% CI: 1.4-63.198, previous stroke with additional comorbidities (cases vs. controls: 7.4% vs. 0.6% (OR: 9.772, 95% CI: 3.302-28.918, gum bleeding (cases vs. controls: 27.4% vs. 11.5% (OR: 1.732, 95% CI: 1.1-2.727, petechiae (cases vs. controls: 56.6% vs. 29.1% (OR: 2.109, 95% CI: 1.411-3.153, and platelet count <50×109 cells/L (cases vs. controls: 53.1% vs. 25.8% (OR: 3.419, 95% CI: 2.103-5.558 were independent predictors of GI bleeding in patients with dengue virus infection.Our study is the first to disclose that end stage renal disease and previous stroke, with additional comorbidities, were strongly significant associated with the risk of GI bleeding in patients with dengue virus infection. Identification of these risk factors can be incorporated into the patient assessment and management protocol

  4. Inhibitory effect of glutathione on oxidative liver injury induced by dengue virus serotype 2 infections in mice.

    Directory of Open Access Journals (Sweden)

    Juan Wang

    Full Text Available The pathogenesis of dengue virus (DV infection has not been completely defined and change of redox status mediated by depletion of glutathione (GSH in host cell is a common result of viral infection. Our previous study has demonstrated that DV serotype 2 (DV2 infection alters host intracellular GSH levels, and exogenous GSH inhibits viral production by modulating the activity of NF-κB in HepG2 cells. GSH is the most powerful intracellular antioxidant and involved in viral infections. Thus, this study was to investigate whether DV2 infection can induce alteration in redox balance and effect of GSH on the disease in HepG2 xenografts SCID mice. Our results revealed that mice infected with DV2 showed alterations in oxidative stress by increasing the level of malondialdehyde (MDA, an end product of lipid peroxidation, and GSSG/GSH ratio. DV2-infected mice also showed a decrease in the activity of catalase (CAT and total superoxide dismutase (T-SOD in the serum and/or observed organs, especially the liver. Moreover, DV2 infection resulted in elevated serum levels of the cytokines tumor necrosis factor-α and interlukin-6 and obvious histopathological changes in the liver. The administration of exogenous GSH significantly reversed all of the aforementioned pathological changes and prevented significant liver damage. Furthermore, in vitro treatment of HepG2 cells with antioxidants such as GSH inhibited viral entry as well as the production of reactive oxygen species in HepG2 cells. These results suggest that GSH prevents DV2-induced oxidative stress and liver injury in mice by inhibiting proinflammatory cytokine production, and GSH and may be a promising therapeutic agent for prevention of oxidative liver damage during DV infection.

  5. The Medicinal Chemistry of Dengue Virus.

    Science.gov (United States)

    Behnam, Mira A M; Nitsche, Christoph; Boldescu, Veaceslav; Klein, Christian D

    2016-06-23

    The dengue virus and related flaviviruses are an increasing global health threat. In this perspective, we comment on and review medicinal chemistry efforts aimed at the prevention or treatment of dengue infections. We include target-based approaches aimed at viral or host factors and results from phenotypic screenings in cellular assay systems for viral replication. This perspective is limited to the discussion of results that provide explicit chemistry or structure-activity relationship (SAR), or appear to be of particular interest to the medicinal chemist for other reasons. The discovery and development efforts discussed here may at least partially be extrapolated toward other emerging flaviviral infections, such as West Nile virus. Therefore, this perspective, although not aimed at flaviviruses in general, should also be able to provide an overview of the medicinal chemistry of these closely related infectious agents.

  6. Amino acid changes within the E protein hinge region that affect dengue virus type 2 infectivity and fusion

    International Nuclear Information System (INIS)

    Butrapet, Siritorn; Childers, Thomas; Moss, Kelley J.; Erb, Steven M.; Luy, Betty E.; Calvert, Amanda E.; Blair, Carol D.; Roehrig, John T.; Huang, Claire Y.-H.

    2011-01-01

    Fifteen mutant dengue viruses were engineered and used to identify AAs in the molecular hinge of the envelope protein that are critical to viral infection. Substitutions at Q52, A54, or E133 reduced infectivity in mammalian cells and altered the pH threshold of fusion. Mutations at F193, G266, I270, or G281 affected viral replication in mammalian and mosquito cells, but only I270W had reduced fusion activity. T280Y affected the pH threshold for fusion and reduced replication in C6/36 cells. Three different mutations at L135 were lethal in mammalian cells. Among them, L135G abrogated fusion and reduced replication in C6/36 cells, but only slightly reduced the mosquito infection rate. Conversely, L135W replicated well in C6/36 cells, but had the lowest mosquito infection rate. Possible interactions between hinge residues 52 and 277, or among 53, 135, 170, 186, 265, and 276 required for hinge function were discovered by sequence analysis to identify compensatory mutations.

  7. Co-circulation of Dengue and Chikungunya Viruses, Al Hudaydah, Yemen, 2012.

    Science.gov (United States)

    Rezza, Giovanni; El-Sawaf, Gamal; Faggioni, Giovanni; Vescio, Fenicia; Al Ameri, Ranya; De Santis, Riccardo; Helaly, Ghada; Pomponi, Alice; Metwally, Dalia; Fantini, Massimo; Qadi, Hussein; Ciccozzi, Massimo; Lista, Florigio

    2014-08-01

    We investigated 400 cases of dengue-like illness in persons hospitalized during an outbreak in Al Hudaydah, Yemen, in 2012. Overall, 116 dengue and 49 chikungunya cases were diagnosed. Dengue virus type 2 was the predominant serotype. The co-circulation of these viruses indicates that mosquitoborne infections represent a public health threat in Yemen.

  8. Prior Exposure to Zika Virus Significantly Enhances Peak Dengue-2 Viremia in Rhesus Macaques

    OpenAIRE

    George, Jeffy; Valiant, William G.; Mattapallil, Mary J.; Walker, Michelle; Huang, Yan-Jang S.; Vanlandingham, Dana L.; Misamore, John; Greenhouse, Jack; Weiss, Deborah E.; Verthelyi, Daniela; Higgs, Stephen; Andersen, Hanne; Lewis, Mark G.; Mattapallil, Joseph J.

    2017-01-01

    Structural and functional homologies between the Zika and Dengue viruses? envelope proteins raise the possibility that cross-reactive antibodies induced following Zika virus infection might enhance subsequent Dengue infection. Using the rhesus macaque model we show that prior infection with Zika virus leads to a significant enhancement of Dengue-2 viremia that is accompanied by neutropenia, lympocytosis, hyperglycemia, and higher reticulocyte counts, along with the activation of pro-inflammat...

  9. Management of a patient with dengue virus infection and tetralogy of Fallot

    Science.gov (United States)

    Arfijanto, M. V.; Oktiawan, E.; Purwati; Hadi, U.

    2018-03-01

    TOF belongs to cyanotic heart disease group, which has polycythemia and a high baseline hematocrit. A heart defect that features four problems:a hole between the lower chambers of the heart, an obstruction from the heart to the lungs, the aorta lies over the hole in the lower chambers, the muscle surrounding the lower right chamber becomes overly thickened. Dengue viral infection in patients with TOF would have a greater potential for the occurrence of heart failure because the baseline of hematocrit is already higher compare with non-congenital heart disease. A 22-year-old man complains offever and nausea since three days before hospitalized. The principal treatment is enough rest and rehydration to achieve normal range of hematocrit (around 65%) and to avoid drugs that may precipitate bleeding (like salicylic acid).In the management of this patient, we should be more careful because there wascomorbid with TOF. The focus of the management is to prevent dehydration during the critical phase and aware of overhydration in the recovery phase.

  10. A comparative hospital-based observational study of mono- and co-infections of malaria, dengue virus and scrub typhus causing acute undifferentiated fever.

    Science.gov (United States)

    Ahmad, S; Dhar, M; Mittal, G; Bhat, N K; Shirazi, N; Kalra, V; Sati, H C; Gupta, V

    2016-04-01

    Positive serology for dengue and/or scrub typhus infection with/without positive malarial smear (designated as mixed or co-infection) is being increasingly observed during epidemics of acute undifferentiated febrile illnesses (AUFIs). We planned to study the clinical and biochemical spectrum of co-infections with Plasmodium sp., dengue virus and scrub typhus and compare these with mono-infection by the same organisms. During the period from December 2012 to December 2013, all cases presenting with AUFIs to a single medical unit of a referral centre in Garhwal region of the north Indian state of Uttarakhand were retrospectively selected and categorised aetiologically as co-infections, malaria, dengue or scrub typhus. The groups thus created were compared in terms of demographic, clinical, biochemical and outcome parameters. The co-infection group (n = 49) was associated with milder clinical manifestations, fewer, milder and non-progressive organ dysfunction, and lesser need for intensive care, mechanical ventilation and dialysis as compared to mono-infections. When co-infections were sub-grouped and compared with the relevant mono-infections, there were differences in certain haematological and biochemical parameters; however, this difference did not translate into differential outcomes. Scrub typhus mono-infection was associated with severe disease in terms of both morbidity and mortality. Malaria, dengue and scrub typhus should be routinely tested in all patients with AUFIs. Co-infections, whether true or due to serological cross-reactivity, appear to be a separate entity so far as presentation and morbidity is concerned. Further insight is needed into the mechanism and identification of the protective infection.

  11. Detection of dengue virus type 4 in Easter Island, Chile.

    Science.gov (United States)

    Fernández, J; Vera, L; Tognarelli, J; Fasce, R; Araya, P; Villagra, E; Roos, O; Mora, J

    2011-10-01

    We report the detection of dengue virus type 4 (DENV-4) for the first time in Easter Island, Chile. The virus was detected in serum samples of two patients treated at the Hospital in Easter Island. The two samples were IgM positive, and the infection was confirmed by RT-PCR and genetic sequencing; viral isolation was possible with one of them. The Easter Island isolates were most closely related to genotype II of dengue type 4.

  12. Comparative proteomics reveals that YK51, a 4-Hydroxypandurantin-A analogue, downregulates the expression of proteins associated with dengue virus infection

    Directory of Open Access Journals (Sweden)

    Wei-Lian Tan

    2018-01-01

    Full Text Available Dengue is endemic throughout tropical and subtropical regions of the world. Currently, there is no clinically approved therapeutic drug available for this acute viral infection. Although the first dengue vaccine Dengvaxia has been approved for use in certain countries, it is limited to those without a previous dengue infection while the safety and efficacy of the vaccine in those elderly and younger children still need to be identified. Therefore, it is becoming increasingly important to develop therapeutics/drugs to combat dengue virus (DENV infection. YK51 is a synthetic analogue of 4-Hydroxypandurantin A (a compound found in the crude extract of the rhizomes of Boesenbergia rotunda that has been extensively studied by our research group. It has been shown to possess outstanding antiviral activity due to its inhibitory activity against NS2B/NS3 DENV2 protease. However, it is not known how YK51 affects the proteome of DENV infected cells. Therefore, we performed a comparative proteomics analysis to identify changes in protein expression in DENV infected HepG2 cells treated with YK51. Classical two-dimensional gel electrophoresis followed by protein identification using tandem mass spectrometry was employed in this study. Thirty proteins were found to be down-regulated with YK51 treatment. In silico analysis predicted that the down-regulation of eight of these proteins may inhibit viral infection. Our results suggested that apart from inhibiting the NS2B/NS3 DENV2 protease, YK51 may also be causing the down-regulation of a number of proteins that may be responsible in, and/or essential to virus infection. However, functional characterization of these proteins will be necessary before we can conclusively determine their roles in DENV infection.

  13. Comparative proteomics reveals that YK51, a 4-Hydroxypandurantin-A analogue, downregulates the expression of proteins associated with dengue virus infection.

    Science.gov (United States)

    Tan, Wei-Lian; Lee, Yean Kee; Ho, Yen Fong; Yusof, Rohana; Abdul Rahman, Noorsaadah; Karsani, Saiful Anuar

    2018-01-01

    Dengue is endemic throughout tropical and subtropical regions of the world. Currently, there is no clinically approved therapeutic drug available for this acute viral infection. Although the first dengue vaccine Dengvaxia has been approved for use in certain countries, it is limited to those without a previous dengue infection while the safety and efficacy of the vaccine in those elderly and younger children still need to be identified. Therefore, it is becoming increasingly important to develop therapeutics/drugs to combat dengue virus (DENV) infection. YK51 is a synthetic analogue of 4-Hydroxypandurantin A (a compound found in the crude extract of the rhizomes of Boesenbergia rotunda ) that has been extensively studied by our research group. It has been shown to possess outstanding antiviral activity due to its inhibitory activity against NS2B/NS3 DENV2 protease. However, it is not known how YK51 affects the proteome of DENV infected cells. Therefore, we performed a comparative proteomics analysis to identify changes in protein expression in DENV infected HepG2 cells treated with YK51. Classical two-dimensional gel electrophoresis followed by protein identification using tandem mass spectrometry was employed in this study. Thirty proteins were found to be down-regulated with YK51 treatment. In silico analysis predicted that the down-regulation of eight of these proteins may inhibit viral infection. Our results suggested that apart from inhibiting the NS2B/NS3 DENV2 protease, YK51 may also be causing the down-regulation of a number of proteins that may be responsible in, and/or essential to virus infection. However, functional characterization of these proteins will be necessary before we can conclusively determine their roles in DENV infection.

  14. Dengue virus infection induces broadly cross-reactive human IgM antibodies that recognize intact virions in humanized BLT-NSG mice.

    Science.gov (United States)

    Jaiswal, Smita; Smith, Kenneth; Ramirez, Alejandro; Woda, Marcia; Pazoles, Pamela; Shultz, Leonard D; Greiner, Dale L; Brehm, Michael A; Mathew, Anuja

    2015-01-01

    The development of small animal models that elicit human immune responses to dengue virus (DENV) is important since prior immunity is a major risk factor for developing severe dengue disease. This study evaluated anti-DENV human antibody (hAb) responses generated from immortalized B cells after DENV-2 infection in NOD-scid IL2rγ(null) mice that were co-transplanted with human fetal thymus and liver tissues (BLT-NSG mice). DENV-specific human antibodies predominantly of the IgM isotype were isolated during acute infection and in convalescence. We found that while a few hAbs recognized the envelope protein produced as a soluble recombinant, a number of hAbs only recognized epitopes on intact virions. The majority of the hAbs isolated during acute infection and in immune mice were serotype-cross-reactive and poorly neutralizing. Viral titers in immune BLT-NSG mice were significantly decreased after challenge with a clinical strain of dengue. DENV-specific hAbs generated in BLT-NSG mice share some of the characteristics of Abs isolated in humans with natural infection. Humanized BLT-NSG mice provide an attractive preclinical platform to assess the immunogenicity of candidate dengue vaccines. © 2014 by the Society for Experimental Biology and Medicine.

  15. Dengue Virus-Infected Dendritic Cells, but Not Monocytes, Activate Natural Killer Cells through a Contact-Dependent Mechanism Involving Adhesion Molecules.

    Science.gov (United States)

    Costa, Vivian Vasconcelos; Ye, Weijian; Chen, Qingfeng; Teixeira, Mauro Martins; Preiser, Peter; Ooi, Eng Eong; Chen, Jianzhu

    2017-08-01

    Natural killer (NK) cells play a protective role against dengue virus (DENV) infection, but the cellular and molecular mechanisms are not fully understood. Using an optimized humanized mouse model, we show that human NK cells, through the secretion of gamma interferon (IFN-γ), are critical in the early defense against DENV infection. Depletion of NK cells or neutralization of IFN-γ leads to increased viremia and more severe thrombocytopenia and liver damage in humanized mice. In vitro studies using autologous human NK cells show that DENV-infected monocyte-derived dendritic cells (MDDCs), but not monocytes, activate NK cells in a contact-dependent manner, resulting in upregulation of CD69 and CD25 and secretion of IFN-γ. Blocking adhesion molecules (LFA-1, DNAM-1, CD2, and 2β4) on NK cells abolishes NK cell activation, IFN-γ secretion, and the control of DENV replication. NK cells activated by infected MDDCs also inhibit DENV infection in monocytes. These findings show the essential role of human NK cells in protection against acute DENV infection in vivo , identify adhesion molecules and dendritic cells required for NK cell activation, and delineate the sequence of events for NK cell activation and protection against DENV infection. IMPORTANCE Dengue is a mosquito-transmitted viral disease with a range of symptoms, from mild fever to life-threatening dengue hemorrhagic fever. The diverse disease manifestation is thought to result from a complex interplay between viral and host factors. Using mice engrafted with a human immune system, we show that human NK cells inhibit virus infection through secretion of the cytokine gamma interferon and reduce disease pathogenesis, including depletion of platelets and liver damage. During a natural infection, DENV initially infects dendritic cells in the skin. We find that NK cells interact with infected dendritic cells through physical contact mediated by adhesion molecules and become activated before they can control

  16. Molecular epidemiology of type 1 and 2 dengue viruses in Brazil from 1988 to 2001

    OpenAIRE

    Pires Neto,R.J.; Lima,D.M.; de Paula,S.O.; Lima,C.M.; Rocco,I.M.; Fonseca,B.A.L.

    2005-01-01

    Dengue is a mosquito-borne viral infection that in recent decades has become a major international public health concern. Epidemic dengue fever reemerged in Brazil in 1981. Since 1990 more than one dengue virus serotype has been circulating in this tropical country and increasing rates of dengue hemorrhagic fever and dengue shock syndrome have been detected every year. Some evidence supports the association between the introduction of a new serotype and/or genotype in a region and the appeara...

  17. Ecg manifestations in dengue infection

    International Nuclear Information System (INIS)

    Tarique, S.; Murtaza, G.; Asif, S.; Qureshi, I.H.

    2013-01-01

    To determine the frequency of ECG changes in patients with dengue fever and dengue hemorrhagic fever. Place of study: Department of Medicine, Mayo Hospital Lahore Duration of study: September to November 201 Study design: Cross sectional analytical study Patient and methods: 116 patients with dengue infection were enrolled in the study. Their clinical presentation and examination was duly noted. Each patient had baseline and then regular monitoring of blood counts, metabolic profile and fluid status. Patients with Dengue Hemorrhagic fever underwent radiological examination in form of chest radiograph and ultrasound abdomen. ECG was carried out in all patients. Results: Out of 116 patients, 61(52.6%) suffered from Dengue Fever and 55(47.4%) had Dengue Hemorrhagic Fever. Overall 78 patients had normal ECG. Abnormal ECG findings like tachycardia, bradycardia, supraventricular tachycardia, left bundle branch block, ST depression, poor progression of R wave were noted. There was no significant relationship of ECG findings with the disease. Conclusion: ECG changes can occur in dengue infection with or without cardiac symptoms. Commonly noted findings were ST depression and bradycardia. (author)

  18. The Role of Heterotypic DENV-specific CD8+T Lymphocytes in an Immunocompetent Mouse Model of Secondary Dengue Virus Infection.

    Science.gov (United States)

    Talarico, Laura B; Batalle, Juan P; Byrne, Alana B; Brahamian, Jorge M; Ferretti, Adrián; García, Ayelén G; Mauri, Aldana; Simonetto, Carla; Hijano, Diego R; Lawrence, Andrea; Acosta, Patricio L; Caballero, Mauricio T; Paredes Rojas, Yésica; Ibañez, Lorena I; Melendi, Guillermina A; Rey, Félix A; Damonte, Elsa B; Harris, Eva; Polack, Fernando P

    2017-06-01

    Dengue is the most prevalent arthropod-borne viral disease worldwide and is caused by the four dengue virus serotypes (DENV-1-4). Sequential heterologous DENV infections can be associated with severe disease manifestations. Here, we present an immunocompetent mouse model of secondary DENV infection using non mouse-adapted DENV strains to investigate the pathogenesis of severe dengue disease. C57BL/6 mice infected sequentially with DENV-1 (strain Puerto Rico/94) and DENV-2 (strain Tonga/74) developed low platelet counts, internal hemorrhages, and increase of liver enzymes. Cross-reactive CD8 + T lymphocytes were found to be necessary and sufficient for signs of severe disease by adoptively transferring of DENV-1-immune CD8 + T lymphocytes before DENV-2 challenge. Disease signs were associated with production of tumor necrosis factor (TNF)-α and elevated cytotoxicity displayed by heterotypic anti-DENV-1 CD8 + T lymphocytes. These findings highlight the critical role of heterotypic anti-DENV CD8 + T lymphocytes in manifestations of severe dengue disease. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Modulation of Dengue/Zika Virus Pathogenicity by Antibody-Dependent Enhancement and Strategies to Protect Against Enhancement in Zika Virus Infection

    Directory of Open Access Journals (Sweden)

    Rekha Khandia

    2018-04-01

    Full Text Available Antibody-dependent enhancement (ADE is a phenomenon in which preexisting poorly neutralizing antibodies leads to enhanced infection. It is a serious concern with mosquito-borne flaviviruses such as Dengue virus (DENV and Zika virus (ZIKV. In vitro experimental evidences have indicated the preventive, as well as a pathogenicity-enhancing role, of preexisting DENV antibodies in ZIKV infections. ADE has been confirmed in DENV but not ZIKV infections. Principally, the Fc region of the anti-DENV antibody binds with the fragment crystallizable gamma receptor (FcγR, and subsequent C1q interactions and immune effector functions are responsible for the ADE. In contrast to normal DENV infections, with ADE in DENV infections, inhibition of STAT1 phosphorylation and a reduction in IRF-1 gene expression, NOS2 levels, and RIG-1 and MDA-5 expression levels occurs. FcγRIIA is the most permissive FcγR for DENV-ADE, and under hypoxic conditions, hypoxia-inducible factor-1 alpha transcriptionally enhances expression levels of FcγRIIA, which further enhances ADE. To produce therapeutic antibodies with broad reactivity to different DENV serotypes, as well as to ZIKV, bispecific antibodies, Fc region mutants, modified Fc regions, and anti-idiotypic antibodies may be engineered. An in-depth understanding of the immunological and molecular mechanisms of DENV-ADE of ZIKV pathogenicity will be useful for the design of common and safe therapeutics and prophylactics against both viral pathogens. The present review discusses the role of DENV antibodies in modulating DENV/ZIKV pathogenicity/infection and strategies to counter ADE to protect against Zika infection.

  20. Elevated plasma levels of the long pentraxin, pentraxin 3, in severe dengue virus infections

    NARCIS (Netherlands)

    Mairuhu, Albert T. A.; Peri, Giuseppe; Setiati, Tatty E.; Hack, C. Erik; Koraka, Penelopie; Soemantri, Augustinus; Osterhaus, Albert D. M. E.; Brandjes, Dees P. M.; van der Meer, Jos W. M.; Mantovani, Alberto; van Gorp, Eric C. M.

    2005-01-01

    C-reactive protein is one of the most widely used indicators of the response of acute-phase proteins. The measurement of C-reactive protein in dengue, however, is clinically not useful, because of marginally elevated levels and absent association with disease severity. The prototypic long pentraxin,

  1. Elevated plasma levels of the long pentraxin, pentraxin 3, in severe dengue virus infections

    NARCIS (Netherlands)

    Mairuhu, ATA; Peri, G; Setiati, TE; Hack, CE; Koraka, P; Soemantri, A; Osterhaus, ADME; Brandjes, DPM; van der Meer, JWM; Mantovani, A; van Gorp, ECM

    C-reactive protein is one of the most widely used indicators of the response of acute-phase proteins. The measurement of C-reactive protein in dengue, however, is clinically not useful, because of marginally elevated levels and absent association with disease severity. The prototypic long pentraxin,

  2. Elevated plasma levels of the long pentraxin, pentraxin 3, in severe dengue virus infections.

    NARCIS (Netherlands)

    Mairuhu, A.T.; Peri, G.; Setiati, T.E.; Hack, C.E.; Koraka, P.; Soemantri, A.; Osterhaus, A.D.; Brandjes, D.P.; Meer, J.W.M. van der; Mantovani, A.; Gorp, E. van

    2005-01-01

    C-reactive protein is one of the most widely used indicators of the response of acute-phase proteins. The measurement of C-reactive protein in dengue, however, is clinically not useful, because of marginally elevated levels and absent association with disease severity. The prototypic long pentraxin,

  3. Properties and Functions of the Dengue Virus Capsid Protein.

    Science.gov (United States)

    Byk, Laura A; Gamarnik, Andrea V

    2016-09-29

    Dengue virus affects hundreds of millions of people each year around the world, causing a tremendous social and economic impact on affected countries. The aim of this review is to summarize our current knowledge of the functions, structure, and interactions of the viral capsid protein. The primary role of capsid is to package the viral genome. There are two processes linked to this function: the recruitment of the viral RNA during assembly and the release of the genome during infection. Although particle assembly takes place on endoplasmic reticulum membranes, capsid localizes in nucleoli and lipid droplets. Why capsid accumulates in these locations during infection remains unknown. In this review, we describe available data and discuss new ideas on dengue virus capsid functions and interactions. We believe that a deeper understanding of how the capsid protein works during infection will create opportunities for novel antiviral strategies, which are urgently needed to control dengue virus infections.

  4. The impact of temperature and Wolbachia infection on vector competence of potential dengue vectors Aedes aegypti and Aedes albopictus in the transmission of dengue virus serotype 1 in southern Taiwan.

    Science.gov (United States)

    Tsai, Cheng-Hui; Chen, Tien-Huang; Lin, Cheo; Shu, Pei-Yun; Su, Chien-Ling; Teng, Hwa-Jen

    2017-11-07

    We evaluated the impact of temperature and Wolbachia infection on vector competence of the local Aedes aegypti and Ae. albopictus populations of southern Taiwan in the laboratory. After oral infection with dengue serotype 1 virus (DENV-1), female mosquitoes were incubated at temperatures of 10, 16, 22, 28 and 34 °C. Subsequently, salivary gland, head, and thorax-abdomen samples were analyzed for their virus titer at 0, 5, 10, 15, 20, 25 and 30 days post-infection (dpi) by real-time RT-PCR. The results showed that Ae. aegypti survived significantly longer and that dengue viral genome levels in the thorax-abdomen (10 3.25 ± 0.53 -10 4.09 ± 0.71 PFU equivalents/ml) and salivary gland samples (10 2.67 ± 0.33 -10 3.89 ± 0.58 PFU equivalents/ml) were significantly higher at high temperature (28-34 °C). The survival of Ae. albopictus was significantly better at 16 or 28 °C, but the virus titers from thorax-abdomen (10 0.70 -10 2.39 ± 1.31 PFU equivalents/ml) and salivary gland samples (10 0.12 ± 0.05 -10 1.51 ± 0.31 PFU equivalents/ml) were significantly higher at 22-28 °C. Within viable temperature ranges, the viruses were detectable after 10 dpi in salivary glands and head tissues in Ae. aegypti and after 5-10 dpi in Ae. albopictus. Vector competence was measured in Ae. albopictus with and without Wolbachia at 28 °C. Wolbachia-infected mosquitoes survived significantly better and carried lower virus titers than Wolbachia-free mosquitoes. Wolbachia coinfections (92.8-97.2%) with wAlbA and wAlbB strains were commonly found in a wild population of Ae. albopictus. In southern Taiwan, Ae. aegypti is the main vector of dengue and Ae. albopictus has a non-significant role in the transmission of dengue virus due to the high prevalence of Wolbachia infection in the local mosquito population of southern Taiwan.

  5. Therapeutic efficacy of antibodies lacking Fcγ receptor binding against lethal dengue virus infection is due to neutralizing potency and blocking of enhancing antibodies [corrected].

    Directory of Open Access Journals (Sweden)

    Katherine L Williams

    2013-02-01

    Full Text Available Dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS are life-threatening complications following infection with one of the four serotypes of dengue virus (DENV. At present, no vaccine or antiviral therapies are available against dengue. Here, we characterized a panel of eight human or mouse-human chimeric monoclonal antibodies (MAbs and their modified variants lacking effector function and dissected the mechanism by which some protect against antibody-enhanced lethal DENV infection. We found that neutralizing modified MAbs that recognize the fusion loop or the A strand epitopes on domains II and III of the envelope protein, respectively, act therapeutically by competing with and/or displacing enhancing antibodies. By analyzing these relationships, we developed a novel in vitro suppression-of-enhancement assay that predicts the ability of modified MAbs to act therapeutically against antibody-enhanced disease in vivo. These studies provide new insight into the biology of DENV pathogenesis and the requirements for antibodies to treat lethal DENV disease.

  6. Acute neuromuscular weakness associated with dengue infection

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    Harmanjit Singh Hira

    2012-01-01

    Full Text Available Background: Dengue infections may present with neurological complications. Whether these are due to neuromuscular disease or electrolyte imbalance is unclear. Materials and Methods: Eighty-eight patients of dengue fever required hospitalization during epidemic in year 2010. Twelve of them presented with acute neuromuscular weakness. We enrolled them for study. Diagnosis of dengue infection based on clinical profile of patients, positive serum IgM ELISA, NS1 antigen, and sero-typing. Complete hemogram, kidney and liver functions, serum electrolytes, and creatine phosphokinase (CPK were tested. In addition, two patients underwent nerve conduction velocity (NCV test and electromyography. Results: Twelve patients were included in the present study. Their age was between 18 and 34 years. Fever, myalgia, and motor weakness of limbs were most common presenting symptoms. Motor weakness developed on 2 nd to 4 th day of illness in 11 of 12 patients. In one patient, it developed on 10 th day of illness. Ten of 12 showed hypokalemia. One was of Guillain-Barré syndrome and other suffered from myositis; they underwent NCV and electromyography. Serum CPK and SGOT raised in 8 out of 12 patients. CPK of patient of myositis was 5098 IU. All of 12 patients had thrombocytopenia. WBC was in normal range. Dengue virus was isolated in three patients, and it was of serotype 1. CSF was normal in all. Within 24 hours, those with hypokalemia recovered by potassium correction. Conclusions: It was concluded that the dengue virus infection led to acute neuromuscular weakness because of hypokalemia, myositis, and Guillain-Barré syndrome. It was suggested to look for presence of hypokalemia in such patients.

  7. Roles of Interferons in Pregnant Women with Dengue Infection: Protective or Dangerous Factors

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    Hao Zhang

    2017-01-01

    Full Text Available Dengue infection is a serious public health problem in tropical and subtropical areas. With the recent outbreaks of Zika disease and its reported correlation with microcephaly, the large number of pregnancies with dengue infection has become a serious concern. This review describes the epidemiological characteristics of pregnancy with dengue and the initial immune response to dengue infection, especially in IFNs production in this group of patients. Dengue is much more prevalent in pregnant women compared with other populations. The severity of dengue is correlated with the level of IFNs, while the serum IFN level must be sufficiently high to maintain the pregnancy and to inhibit virus replication.

  8. Dengue Virus Type 2 in Travelers Returning to Japan from Sri Lanka, 2017.

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    Tsuboi, Motoyuki; Kutsuna, Satoshi; Maeki, Takahiro; Taniguchi, Satoshi; Tajima, Shigeru; Kato, Fumihiro; Lim, Chang-Kweng; Saijo, Masayuki; Takaya, Saho; Katanami, Yuichi; Kato, Yasuyuki; Ohmagari, Norio

    2017-11-01

    In June 2017, dengue virus type 2 infection was diagnosed in 2 travelers returned to Japan from Sri Lanka, where the country's largest dengue fever outbreak is ongoing. Travelers, especially those previously affected by dengue fever, should take measures to avoid mosquito bites.

  9. Strand-like structures and the nonstructural proteins 5, 3 and 1 are present in the nucleus of mosquito cells infected with dengue virus.

    Science.gov (United States)

    Reyes-Ruiz, José M; Osuna-Ramos, Juan F; Cervantes-Salazar, Margot; Lagunes Guillen, Anel E; Chávez-Munguía, Bibiana; Salas-Benito, Juan S; Del Ángel, Rosa M

    2018-02-01

    Dengue virus (DENV) is an arbovirus, which replicates in the endoplasmic reticulum. Although replicative cycle takes place in the cytoplasm, some viral proteins such as NS5 and C are translocated to the nucleus during infection in mosquitoes and mammalian cells. To localized viral proteins in DENV-infected C6/36 cells, an immunofluorescence (IF) and immunoelectron microscopy (IEM) analysis were performed. Our results indicated that C, NS1, NS3 and NS5 proteins were found in the nucleus of DENV-infected C6/36 cells. Additionally, complex structures named strand-like structures (Ss) were observed in the nucleus of infected cells. Interestingly, the NS5 protein was located in these structures. Ss were absent in mock-infected cells, suggesting that DENV induces their formation in the nucleus of infected mosquito cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. The epidemiology of dengue virus infection among urban, jungle, and rural populations in the Amazon region of Peru.

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    Hayes, C G; Phillips, I A; Callahan, J D; Griebenow, W F; Hyams, K C; Wu, S J; Watts, D M

    1996-10-01

    The first confirmed outbreak of dengue fever in Peru occurred during 1990 in Iquitos, a city of approximately 300,000 residents in the Amazon region. Because of the apparent establishment of endemic transmission of this mosquito-borne viral disease following the outbreak, epidemiologic studies were initiated in 1992. Blood specimens and data on demographic, environmental, and medical history factors were collected from volunteers in an urban sector of Iquitos, in a rural area on the outskirts of Iquitos, and in three nearby jungle communities. A follow-up blood specimen was obtained approximately one year later from a sample of subjects. Sera were tested for dengue IgG antibody by an enzyme-linked immunosorbent assay, and specificity was verified using a plaque-reduction neutralization test. Dengue antibody prevalence was 66% in the urban population, 26% in the rural population, and 32-67% in the three jungle areas. A significant association was found between age and antibody prevalence, with a steady increase in prevalence from 18% among subjects less than five years of age to greater than 90% for subjects more than 50 years old. Increased antibody prevalence also was associated with urban and jungle residence and with a piped source of household drinking water. Seroconversions were documented in four of five surveyed communities. These results indicate that dengue virus transmission continues in and around Iquitos and suggest that transmission also occurred prior to the 1990 epidemic.

  11. Understanding the Dengue Viruses and Progress towards Their Control

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    Gould, Ernest A.

    2013-01-01

    Traditionally, the four dengue virus serotypes have been associated with fever, rash, and the more severe forms, haemorrhagic fever and shock syndrome. As our knowledge as well as understanding of these viruses increases, we now recognise not only that they are causing increasing numbers of human infections but also that they may cause neurological and other clinical complications, with sequelae or fatal consequences. In this review we attempt to highlight some of these features in the context of dengue virus pathogenesis. We also examine some of the efforts currently underway to control this “scourge” of the tropical and subtropical world. PMID:23936833

  12. Clinical Features of and Risk Factors for Rhabdomyolysis Among Adult Patients with Dengue Virus Infection

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    Huang, Shi-Yu; Lee, Ing-Kit; Liu, Jien-Wei; Kung, Chia-Te; Wang, Lin

    2015-01-01

    Among 1,076 dengue patients, 9 patients with rhabdomyolysis and 1,067 patients without rhabdomyolysis (controls) were retrospectively analyzed. Of nine patients with rhabdomyolysis, the most commonly reported symptom other than fever was myalgia; dengue hemorrhagic fever (DHF) was found in seven cases, and acute kidney injury was found in six cases. Furthermore, one (11.1%) patient died. The median duration from hospital admission to rhabdomyolysis diagnosis was 3 days. Patients with rhabdomyolysis had higher age, proportion of men, prevalence of hypertension, frequency of myalgia, and incidences of DHF, pleural effusion, and acute kidney injury than controls. Multivariate analysis showed that hypertension (odds ratio [OR] = 14.270), myalgia (OR = 20.377), and acute kidney injury (OR = 65.547) were independent risk factors for rhabdomyolysis. Comparison of cytokine/chemokine concentrations in 101 DHF patients, including those with (N = 4) and without (N = 97) rhabdomyolysis, showed that interleukin-6 and tumor necrosis factor-α levels were significantly increased in the former. PMID:25349377

  13. Autophagic machinery activated by dengue virus enhances virus replication

    International Nuclear Information System (INIS)

    Lee, Y.-R.; Lei, H.-Y.; Liu, M.-T.; Wang, J.-R.; Chen, S.-H.; Jiang-Shieh, Y.-F.; Lin, Y.-S.; Yeh, T.-M.; Liu, C.-C.; Liu, H.-S.

    2008-01-01

    Autophagy is a cellular response against stresses which include the infection of viruses and bacteria. We unravel that Dengue virus-2 (DV2) can trigger autophagic process in various infected cell lines demonstrated by GFP-LC3 dot formation and increased LC3-II formation. Autophagosome formation was also observed under the transmission electron microscope. DV2-induced autophagy further enhances the titers of extracellular and intracellular viruses indicating that autophagy can promote viral replication in the infected cells. Moreover, our data show that ATG5 protein is required to execute DV2-induced autophagy. All together, we are the first to demonstrate that DV can activate autophagic machinery that is favorable for viral replication

  14. Integrated analysis of miRNAs and transcriptomes in Aedes albopictus midgut reveals the differential expression profiles of immune-related genes during dengue virus serotype-2 infection.

    Science.gov (United States)

    Liu, Yan-Xia; Li, Fen-Xiang; Liu, Zhuan-Zhuan; Jia, Zhi-Rong; Zhou, Yan-He; Zhang, Hao; Yan, Hui; Zhou, Xian-Qiang; Chen, Xiao-Guang

    2016-06-01

    Mosquito microRNAs (miRNAs) are involved in host-virus interaction, and have been reported to be altered by dengue virus (DENV) infection in Aedes albopictus (Diptera: Culicidae). However, little is known about the molecular mechanisms of Aedes albopictus midgut-the first organ to interact with DENV-involved in its resistance to DENV. Here we used high-throughput sequencing to characterize miRNA and messenger RNA (mRNA) expression patterns in Aedes albopictus midgut in response to dengue virus serotype 2. A total of three miRNAs and 777 mRNAs were identified to be differentially expressed upon DENV infection. For the mRNAs, we identified 198 immune-related genes and 31 of them were differentially expressed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses also showed that the differentially expressed immune-related genes were involved in immune response. Then the differential expression patterns of six immune-related genes and three miRNAs were confirmed by real-time reverse transcription polymerase chain reaction. Furthermore, seven known miRNA-mRNA interaction pairs were identified by aligning our two datasets. These analyses of miRNA and mRNA transcriptomes provide valuable information for uncovering the DENV response genes and provide a basis for future study of the resistance mechanisms in Aedes albopictus midgut. © 2016 Institute of Zoology, Chinese Academy of Sciences.

  15. Decrease in Dengue virus-2 infection and reduction of cytokine/chemokine production by Uncaria guianensis in human hepatocyte cell line Huh-7

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    Cíntia da Silva Mello

    Full Text Available ABSTRACT BACKGROUND Dengue fever may present hemorrhages and cavitary effusions as result of exacerbated immune responses. We investigated hydro-alcoholic extracts from leaves (UGL and bark (UGB of the medicinal species Uncaria guinanensis with respect to antiviral effects in Dengue virus (DENV infection and in immunological parameters associated with in vivo physiopathological features. METHODS Chemical profiles from UGB or UGL were compared in thin layer chromatography and 1H nuclear magnetic resonance using flavonoid compounds and a pentacyclic oxindole alkaloid-enriched fraction as references. DENV-2-infected hepatocytes (Huh-7 were treated with extracts. Cell viability, DENV antigens and immunological factors were detected by enzyme-linked immunosorbent assay (ELISA or flow cytometry. FINDINGS The UGL mainly differed from UGB by selectively containing the flavonoid kaempferitrin. UGB and UGL improved hepatocyte viability. Both extracts reduced intracellular viral antigen and inhibited the secretion of viral non-structural protein (NS1, which is indicative of viral replication. Reduction in secretion of macrophage migration inhibitory factor was achieved by UGB, of interleukin-6 by UGL, and of interleukin-8 by both UGB and UGL. MAIN CONCLUSIONS The U. guianensis extracts presented, antiviral and immunomodulatory effects for DENV and possibly a hepatocyte-protective activity. Further studies may be performed to consider these products as potential candidates for the development of an herbal product for the future treatment of dengue.

  16. Decrease in Dengue virus-2 infection and reduction of cytokine/chemokine production by Uncaria guianensis in human hepatocyte cell line Huh-7.

    Science.gov (United States)

    Mello, Cíntia da Silva; Valente, Ligia Maria Marino; Wolff, Thiago; Lima-Junior, Raimundo Sousa; Fialho, Luciana Gomes; Marinho, Cintia Ferreira; Azeredo, Elzinandes Leal; Oliveira-Pinto, Luzia Maria; Pereira, Rita de Cássia Alves; Siani, Antonio Carlos; Kubelka, Claire Fernandes

    2017-06-01

    Dengue fever may present hemorrhages and cavitary effusions as result of exacerbated immune responses. We investigated hydro-alcoholic extracts from leaves (UGL) and bark (UGB) of the medicinal species Uncaria guinanensis with respect to antiviral effects in Dengue virus (DENV) infection and in immunological parameters associated with in vivo physiopathological features. Chemical profiles from UGB or UGL were compared in thin layer chromatography and 1H nuclear magnetic resonance using flavonoid compounds and a pentacyclic oxindole alkaloid-enriched fraction as references. DENV-2-infected hepatocytes (Huh-7) were treated with extracts. Cell viability, DENV antigens and immunological factors were detected by enzyme-linked immunosorbent assay (ELISA) or flow cytometry. The UGL mainly differed from UGB by selectively containing the flavonoid kaempferitrin. UGB and UGL improved hepatocyte viability. Both extracts reduced intracellular viral antigen and inhibited the secretion of viral non-structural protein (NS1), which is indicative of viral replication. Reduction in secretion of macrophage migration inhibitory factor was achieved by UGB, of interleukin-6 by UGL, and of interleukin-8 by both UGB and UGL. MAIN. The U. guianensis extracts presented, antiviral and immunomodulatory effects for DENV and possibly a hepatocyte-protective activity. Further studies may be performed to consider these products as potential candidates for the development of an herbal product for the future treatment of dengue.

  17. Dengue Virus and Its Inhibitors: A Brief Review

    OpenAIRE

    Tian, Yu-Shi; Zhou, Yi; Takagi, Tatsuya; Kameoka, Masanori; Kawashita, Norihito

    2018-01-01

    The global occurrence of viral infectious diseases poses a significant threat to human health. Dengue virus (DENV) infection is one of the most noteworthy of these infections. According to a WHO survey, approximately 400 million people are infected annually; symptoms deteriorate in approximately one percent of cases. Numerous foundational and clinical investigations on viral epidemiology, structure and function analysis, infection source and route, therapeutic targets, vaccines, and therapeut...

  18. Vector competence of Malaysian Aedes albopictus with and without Wolbachia to four dengue virus serotypes.

    Science.gov (United States)

    Joanne, Sylvia; Vythilingam, Indra; Teoh, Boon-Teong; Leong, Cherng-Shii; Tan, Kim-Kee; Wong, Meng-Li; Yugavathy, Nava; AbuBakar, Sazaly

    2017-09-01

    To determine the susceptibility status of Aedes albopictus with and without Wolbachia to the four dengue virus serotypes. Two newly colonised colonies of Ae. albopictus from the wild were used for the study. One colony was naturally infected with Wolbachia while in the other Wolbachia was removed by tetracycline treatment. Both colonies were orally infected with dengue virus-infected fresh blood meal. Dengue virus load was measured using quantitative RT-PCR at four-time intervals in the salivary glands, midguts and ovaries. Wolbachia did not significantly affect Malaysian Ae. albopictus dengue infection or the dissemination rate for all four dengue virus serotypes. Malaysian Ae. albopictus had the highest replication kinetics for DENV-1 and the highest salivary gland and midgut infection rate for DENV-4. Wolbachia, which naturally exists in Malaysian Ae. albopictus, does not significantly affect dengue virus replication. Malaysian Ae. albopictus is susceptible to dengue virus infections and capable of transmitting dengue virus, especially DENV-1 and DENV-4. Removal of Wolbachia from Malaysian Ae. albopictus would not reduce their susceptibility status. © 2017 John Wiley & Sons Ltd.

  19. Spatial and temporal clustering of dengue virus transmission in Thai villages.

    OpenAIRE

    Mammen P Mammen; Chusak Pimgate; Constantianus J M Koenraadt; Alan L Rothman; Jared Aldstadt; Ananda Nisalak; Richard G Jarman; James W Jones; Anon Srikiatkhachorn; Charity Ann Ypil-Butac; Arthur Getis; Suwich Thammapalo; Amy C Morrison; Daniel H Libraty; Sharone Green

    2008-01-01

    Editors' Summary Background. Every year, over 50 million people living in tropical and subtropical urban and semi-urban areas become infected with dengue (a mosquito-borne viral infection) and several hundred thousand develop a potentially lethal complication called dengue hemorrhagic fever. Dengue is caused by four closely related viruses that are transmitted to people through the bites of infected female Aedes aegypti mosquitoes. These day-biting insects, which breed in household water cont...

  20. Small RNA Profiling in Dengue Virus 2-Infected Aedes Mosquito Cells Reveals Viral piRNAs and Novel Host miRNAs.

    Science.gov (United States)

    Miesen, Pascal; Ivens, Alasdair; Buck, Amy H; van Rij, Ronald P

    2016-02-01

    In Aedes mosquitoes, infections with arthropod-borne viruses (arboviruses) trigger or modulate the expression of various classes of viral and host-derived small RNAs, including small interfering RNAs (siRNAs), PIWI interacting RNAs (piRNAs), and microRNAs (miRNAs). Viral siRNAs are at the core of the antiviral RNA interference machinery, one of the key pathways that limit virus replication in invertebrates. Besides siRNAs, Aedes mosquitoes and cells derived from these insects produce arbovirus-derived piRNAs, the best studied examples being viruses from the Togaviridae or Bunyaviridae families. Host miRNAs modulate the expression of a large number of genes and their levels may change in response to viral infections. In addition, some viruses, mostly with a DNA genome, express their own miRNAs to regulate host and viral gene expression. Here, we perform a comprehensive analysis of both viral and host-derived small RNAs in Aedes aegypti Aag2 cells infected with dengue virus 2 (DENV), a member of the Flaviviridae family. Aag2 cells are competent in producing all three types of small RNAs and provide a powerful tool to explore the crosstalk between arboviral infection and the distinct RNA silencing pathways. Interestingly, besides the well-characterized DENV-derived siRNAs, a specific population of viral piRNAs was identified in infected Aag2 cells. Knockdown of Piwi5, Ago3 and, to a lesser extent, Piwi6 results in reduction of vpiRNA levels, providing the first genetic evidence that Aedes PIWI proteins produce DENV-derived small RNAs. In contrast, we do not find convincing evidence for the production of virus-derived miRNAs. Neither do we find that host miRNA expression is strongly changed upon DENV2 infection. Finally, our deep-sequencing analyses detect 30 novel Aedes miRNAs, complementing the repertoire of regulatory small RNAs in this important vector species.

  1. Resveratrol treatment reveals a novel role for HMGB1 in regulation of the type 1 interferon response in dengue virus infection.

    Science.gov (United States)

    Zainal, Nurhafiza; Chang, Chih-Peng; Cheng, Yi-Lin; Wu, Yan-Wei; Anderson, Robert; Wan, Shu-Wen; Chen, Chia-Ling; Ho, Tzong-Shiann; AbuBakar, Sazaly; Lin, Yee-Shin

    2017-02-20

    Dengue is one of the most significant mosquito-borne virus diseases worldwide, particularly in tropical and subtropical regions. This study sought to examine the antiviral activity of resveratrol (RESV), a phytoalexin secreted naturally by plants, against dengue virus (DENV) infection. Our data showed that RESV inhibits the translocation of high mobility group box 1 (HMGB1), a DNA binding protein that normally resides in the nucleus, into the cytoplasm and extracellular milieu. HMGB1 migrates out of the nucleus during DENV infection. This migration is inhibited by RESV treatment and is mediated by induction of Sirt1 which leads to the retention of HMGB1 in the nucleus and consequently helps in the increased production of interferon-stimulated genes (ISGs). Nuclear HMGB1 was found to bind to the promoter region of the ISG and positively regulated the expression of ISG. The enhanced transcription of ISGs by nuclear HMGB1 thus contributes to the antiviral activity of RESV against DENV. To the best of our knowledge, this is the first report to demonstrate that RESV antagonizes DENV replication and that nuclear HMGB1 plays a role in regulating ISG production.

  2. The estimation of imported dengue virus from Thailand.

    Science.gov (United States)

    Polwiang, Sittisede

    2015-01-01

    Dengue fever is one of the important causes of illness among travelers returning from Thailand. The risk of infection depends on the length of stay, activities, and arrival time. Due to globalization, there is a concern that infected travelers may carry dengue virus (DENV) to their country of residence and cause an outbreak. To estimate the infective person-days of travelers returning from Thailand, we developed a model with the following parameters: the probability of travelers being infected, number of arrivals, length of stay of travelers, incubation period, and duration of the infective period. The data used in this study were the dengue incidences in Thailand during 2004-2013 and foreign traveler arrivals in 2013. We estimated the highest infective person-days for each country group. The highest value was from June to August during the rainy season in Thailand for all groups. Infective person-days ranged from 87 to 112 per 100,000 travelers each year. Our results provided a fundamental step toward estimation of the risk of the secondary transmission of DENV in non-epidemic countries via travelers, which can serve as an early warning of a dengue outbreak. The highest infective person-day is associated with the rainy season in Thailand. The increasing number of overseas travelers may increase the risk of global transmission of the DENV. Better understanding of the virus transmission dynamics will enable further quantitative predictions of epidemic risk. © 2015 International Society of Travel Medicine.

  3. Dengue infection in pregnancy and its impact on the placenta

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    Christiane Fernandes Ribeiro

    2017-02-01

    Full Text Available A histopathological and immunohistochemical study was conducted in placental tissues and retained products of conception from 24 patients with confirmed dengue infection during pregnancy. The immunohistochemical assay was positive for dengue virus in 19 placental and three ovular remnants analyzed. The light microscopic findings were signs of hypoxia, choriodeciduitis, deciduitis and intervillositis and the viral antigens were found in cytoplasmic of the trophoblast, villous stroma and decidua. Our results suggest that immunohistochemistry could be used as a laboratory confirmation method for dengue in pregnant women, especially in endemic areas when embedded material is the only material available.

  4. Age-dependent effects of oral infection with dengue virus on Aedes aegypti (Diptera: Culicidae) feeding behavior, survival, oviposition success and fecundity.

    Science.gov (United States)

    Sylvestre, Gabriel; Gandini, Mariana; Maciel-de-Freitas, Rafael

    2013-01-01

    Aedes aegypti is the main vector of dengue, a disease that is increasing its geographical range as well as incidence rates. Despite its public health importance, the effect of dengue virus (DENV) on some mosquito traits remains unknown. Here, we investigated the impact of DENV-2 infection on the feeding behavior, survival, oviposition success and fecundity of Ae. aegypti females. After orally-challenging Ae. aegypti females with a DENV-2 strain using a membrane feeder, we monitored the feeding behavior, survival, oviposition success and fecundity throughout the mosquito lifespan. We observed an age-dependent cost of DENV infection on mosquito feeding behavior and fecundity. Infected individuals took more time to ingest blood from anesthetized mice in the 2(nd) and 3(rd) weeks post-infection, and also longer overall blood-feeding times in the 3(rd) week post-infection, when females were around 20 days old. Often, infected Ae. aegypti females did not lay eggs and when they were laid, smaller number of eggs were laid compared to uninfected controls. A reduction in the number of eggs laid per female was evident starting on the 3(rd) week post-infection. DENV-2 negatively affected mosquito lifespan, since overall the longevity of infected females was halved compared to that of the uninfected control group. The DENV-2 strain tested significantly affected Ae. aegypti traits directly correlated with vectorial capacity or mosquito population density, such as feeding behavior, survival, fecundity and oviposition success. Infected mosquitoes spent more time ingesting blood, had reduced lifespan, laid eggs less frequently, and when they did lay eggs, the clutches were smaller than uninfected mosquitoes.

  5. Age-dependent effects of oral infection with dengue virus on Aedes aegypti (Diptera: Culicidae feeding behavior, survival, oviposition success and fecundity.

    Directory of Open Access Journals (Sweden)

    Gabriel Sylvestre

    Full Text Available BACKGROUND: Aedes aegypti is the main vector of dengue, a disease that is increasing its geographical range as well as incidence rates. Despite its public health importance, the effect of dengue virus (DENV on some mosquito traits remains unknown. Here, we investigated the impact of DENV-2 infection on the feeding behavior, survival, oviposition success and fecundity of Ae. aegypti females. METHODS/PRINCIPAL FINDINGS: After orally-challenging Ae. aegypti females with a DENV-2 strain using a membrane feeder, we monitored the feeding behavior, survival, oviposition success and fecundity throughout the mosquito lifespan. We observed an age-dependent cost of DENV infection on mosquito feeding behavior and fecundity. Infected individuals took more time to ingest blood from anesthetized mice in the 2(nd and 3(rd weeks post-infection, and also longer overall blood-feeding times in the 3(rd week post-infection, when females were around 20 days old. Often, infected Ae. aegypti females did not lay eggs and when they were laid, smaller number of eggs were laid compared to uninfected controls. A reduction in the number of eggs laid per female was evident starting on the 3(rd week post-infection. DENV-2 negatively affected mosquito lifespan, since overall the longevity of infected females was halved compared to that of the uninfected control group. CONCLUSIONS: The DENV-2 strain tested significantly affected Ae. aegypti traits directly correlated with vectorial capacity or mosquito population density, such as feeding behavior, survival, fecundity and oviposition success. Infected mosquitoes spent more time ingesting blood, had reduced lifespan, laid eggs less frequently, and when they did lay eggs, the clutches were smaller than uninfected mosquitoes.

  6. Clinical predictors of dengue fever co-infected with leptospirosis among patients admitted for dengue fever - a pilot study.

    Science.gov (United States)

    Suppiah, Jeyanthi; Chan, Shie-Yien; Ng, Min-Wern; Khaw, Yam-Sim; Ching, Siew-Mooi; Mat-Nor, Lailatul Akmar; Ahmad-Najimudin, Naematul Ain; Chee, Hui-Yee

    2017-06-28

    Dengue and leptospirosis infections are currently two major endemics in Malaysia. Owing to the overlapping clinical symptoms between both the diseases, frequent misdiagnosis and confusion of treatment occurs. As a solution, the present work initiated a pilot study to investigate the incidence related to co-infection of leptospirosis among dengue patients. This enables the identification of more parameters to predict the occurrence of co-infection. Two hundred sixty eight serum specimens collected from patients that were diagnosed for dengue fever were confirmed for dengue virus serotyping by real-time polymerase chain reaction. Clinical, laboratory and demographic data were extracted from the hospital database to identify patients with confirmed leptospirosis infection among the dengue patients. Thus, frequency of co-infection was calculated and association of the dataset with dengue-leptospirosis co-infection was statistically determined. The frequency of dengue co-infection with leptospirosis was 4.1%. Male has higher preponderance of developing the co-infection and end result of shock as clinical symptom is more likely present among co-infected cases. It is also noteworthy that, DENV 1 is the common dengue serotype among all cases identified as dengue-leptospirosis co-infection in this study. The increasing incidence of leptospirosis among dengue infected patients has posed the need to precisely identify the presence of co-infection for the betterment of treatment without mistakenly ruling out either one of them. Thus, anticipating the possible clinical symptoms and laboratory results of dengue-leptospirosis co-infection is essential.

  7. Ability To Serologically Confirm Recent Zika Virus Infection in Areas with Varying Past Incidence of Dengue Virus Infection in the United States and U.S. Territories in 2016.

    Science.gov (United States)

    Lindsey, Nicole P; Staples, J Erin; Powell, Krista; Rabe, Ingrid B; Fischer, Marc; Powers, Ann M; Kosoy, Olga I; Mossel, Eric C; Munoz-Jordan, Jorge L; Beltran, Manuela; Hancock, W Thane; Toews, Karrie-Ann E; Ellis, Esther M; Ellis, Brett R; Panella, Amanda J; Basile, Alison J; Calvert, Amanda E; Laven, Janeen; Goodman, Christin H; Gould, Carolyn V; Martin, Stacey W; Thomas, Jennifer D; Villanueva, Julie; Mataia, Mary L; Sciulli, Rebecca; Gose, Remedios; Whelen, A Christian; Hills, Susan L

    2018-01-01

    Cross-reactivity within flavivirus antibody assays, produced by shared epitopes in the envelope proteins, can complicate the serological diagnosis of Zika virus (ZIKAV) infection. We assessed the utility of the plaque reduction neutralization test (PRNT) to confirm recent ZIKAV infections and rule out misleading positive immunoglobulin M (IgM) results in areas with various levels of past dengue virus (DENV) infection incidence. We reviewed PRNT results of sera collected for diagnosis of ZIKAV infection from 1 January through 31 August 2016 with positive ZIKAV IgM results, and ZIKAV and DENV PRNTs were performed. PRNT result interpretations included ZIKAV, unspecified flavivirus, DENV infection, or negative. For this analysis, ZIKAV IgM was considered false positive for samples interpreted as a DENV infection or negative. In U.S. states, 208 (27%) of 759 IgM-positive results were confirmed to be ZIKAV compared to 11 (21%) of 52 in the U.S. Virgin Islands (USVI), 15 (15%) of 103 in American Samoa, and 13 (11%) of 123 in Puerto Rico. In American Samoa and Puerto Rico, more than 80% of IgM-positive results were unspecified flavivirus infections. The false-positivity rate was 27% in U.S. states, 18% in the USVI, 2% in American Samoa, and 6% in Puerto Rico. In U.S. states, the PRNT provided a virus-specific diagnosis or ruled out infection in the majority of IgM-positive samples. Almost a third of ZIKAV IgM-positive results were not confirmed; therefore, providers and patients must understand that IgM results are preliminary. In territories with historically higher rates of DENV transmission, the PRNT usually could not differentiate between ZIKAV and DENV infections. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

  8. System Dynamics based Dengue modeling environment to simulate evolution of Dengue infection under different climate scenarios

    Science.gov (United States)

    Anwar, R.; Khan, R.; Usmani, M.; Colwell, R. R.; Jutla, A.

    2017-12-01

    Vector borne infectious diseases such as Dengue, Zika and Chikungunya remain a public health threat. An estimate of the World Health Organization (WHO) suggests that about 2.5 billion people, representing ca. 40% of human population,are at increased risk of dengue; with more than 100 million infection cases every year. Vector-borne infections cannot be eradicated since disease causing pathogens survive in the environment. Over the last few decades dengue infection has been reported in more than 100 countries and is expanding geographically. Female Ae. Aegypti mosquito, the daytime active and a major vector for dengue virus, is associated with urban population density and regional climatic processes. However, mathematical quantification of relationships on abundance of vectors and climatic processes remain a challenge, particularly in regions where such data are not routinely collected. Here, using system dynamics based feedback mechanism, an algorithm integrating knowledge from entomological, meteorological and epidemiological processes is developed that has potential to provide ensemble simulations on risk of occurrence of dengue infection in human population. Using dataset from satellite remote sensing, the algorithm was calibrated and validated using actual dengue case data of Iquitos, Peru. We will show results on model capabilities in capturing initiation and peak in the observed time series. In addition, results from several simulation scenarios under different climatic conditions will be discussed.

  9. Molecular epidemiology of type 1 and 2 dengue viruses in Brazil from 1988 to 2001.

    Science.gov (United States)

    Pires Neto, R J; Lima, D M; de Paula, S O; Lima, C M; Rocco, I M; Fonseca, B A L

    2005-06-01

    Dengue is a mosquito-borne viral infection that in recent decades has become a major international public health concern. Epidemic dengue fever reemerged in Brazil in 1981. Since 1990 more than one dengue virus serotype has been circulating in this tropical country and increasing rates of dengue hemorrhagic fever and dengue shock syndrome have been detected every year. Some evidence supports the association between the introduction of a new serotype and/or genotype in a region and the appearance of dengue hemorrhagic fever. In order to study the evolutionary relationships and possible detection of the introduction of new dengue virus genotypes in Brazil in the last years, we analyzed partial nucleotide sequences of 52 Brazilian samples of both dengue type 1 and dengue type 2 isolated from 1988 to 2001 from highly endemic regions. A 240-nucleotide-long sequence from the envelope/nonstructural protein 1 gene junction was used for phylogenetic analysis. After comparing the nucleotide sequences originally obtained in this study to those previously studied by others, and analyzing the phylogenetic trees, we conclude that, after the initial introduction of the currently circulating dengue-1 and dengue-2 genotypes in Brazil, there has been no evidence of introduction of new genotypes since 1988. The increasing number of dengue hemorrhagic fever cases seen in Brazil in the last years is probably associated with secondary infections or with the introduction of new serotypes but not with the introduction of new genotypes.

  10. Molecular epidemiology of type 1 and 2 dengue viruses in Brazil from 1988 to 2001

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    Pires Neto R.J.

    2005-01-01

    Full Text Available Dengue is a mosquito-borne viral infection that in recent decades has become a major international public health concern. Epidemic dengue fever reemerged in Brazil in 1981. Since 1990 more than one dengue virus serotype has been circulating in this tropical country and increasing rates of dengue hemorrhagic fever and dengue shock syndrome have been detected every year. Some evidence supports the association between the introduction of a new serotype and/or genotype in a region and the appearance of dengue hemorrhagic fever. In order to study the evolutionary relationships and possible detection of the introduction of new dengue virus genotypes in Brazil in the last years, we analyzed partial nucleotide sequences of 52 Brazilian samples of both dengue type 1 and dengue type 2 isolated from 1988 to 2001 from highly endemic regions. A 240-nucleotide-long sequence from the envelope/nonstructural protein 1 gene junction was used for phylogenetic analysis. After comparing the nucleotide sequences originally obtained in this study to those previously studied by others, and analyzing the phylogenetic trees, we conclude that, after the initial introduction of the currently circulating dengue-1 and dengue-2 genotypes in Brazil, there has been no evidence of introduction of new genotypes since 1988. The increasing number of dengue hemorrhagic fever cases seen in Brazil in the last years is probably associated with secondary infections or with the introduction of new serotypes but not with the introduction of new genotypes.

  11. Progress in the Identification of Dengue Virus Entry/Fusion Inhibitors

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    Carolina De La Guardia

    2014-01-01

    Full Text Available Dengue fever, a reemerging disease, is putting nearly 2.5 billion people at risk worldwide. The number of infections and the geographic extension of dengue fever infection have increased in the past decade. The disease is caused by the dengue virus, a flavivirus that uses mosquitos Aedes sp. as vectors. The disease has several clinical manifestations, from the mild cold-like illness to the more serious hemorrhagic dengue fever and dengue shock syndrome. Currently, there is no approved drug for the treatment of dengue disease or an effective vaccine to fight the virus. Therefore, the search for antivirals against dengue virus is an active field of research. As new possible receptors and biological pathways of the virus biology are discovered, new strategies are being undertaken to identify possible antiviral molecules. Several groups of researchers have targeted the initial step in the infection as a potential approach to interfere with the virus. The viral entry process is mediated by viral proteins and cellular receptor molecules that end up in the endocytosis of the virion, the fusion of both membranes, and the release of viral RNA in the cytoplasm. This review provides an overview of the targets and progress that has been made in the quest for dengue virus entry inhibitors.

  12. Advances and new insights in the neuropathogenesis of dengue infection

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    Marzia Puccioni-Sohler

    2015-08-01

    Full Text Available Dengue virus (DENV infects approximately 390 million persons every year in more than 100 countries. Reports of neurological complications are more frequently. The objective of this narrative review is to bring up the advances in the dengue neuropathogenesis. DENV can access the nervous system through blood-brain barrier disturbance mediated by cytokine. The blood-cerebrospinal fluid (CSF barrier seems to be also involved, considering the presence of the virus in the CSF of patients with neurological manifestations. As for neurotropism, several studies showed the presence of RNA and viral antigens in brain tissue and CSF in humans. In murine model, different virus mutations were associated to neurovirulence. Despite the advances in the dengue neuropathogenesis, it is still necessary to determine a more appropriate animal model and increase the number of cases of autopsy. The detection of neurovirulence markers may contribute to establish a prognosis, the disease control and vaccine development.

  13. Optimizing celgosivir therapy in mouse models of dengue virus infection of serotypes 1 and 2: The search for a window for potential therapeutic efficacy.

    Science.gov (United States)

    Watanabe, Satoru; Chan, Kitti Wing-Ki; Dow, Geoffrey; Ooi, Eng Eong; Low, Jenny G; Vasudevan, Subhash G

    2016-03-01

    Although the antiviral drug celgosivir, an α-glucosidase I inhibitor, is highly protective when given twice daily to AG129 mice infected with dengue virus, a similar regimen of twice daily dosing did not significantly reduce serum viral loads in patients in a recent clinical trial. This failure presumably might reflect the initiation of treatment when patients were already viremic. To better mimic the clinical setting, we used viruses isolated from patients to develop new mouse models of DENV1 and DENV2 infection and employed the models to test the twice daily treatment, begun either on the day of infection or on the third day post-infection, when the mice had peak of viremia. We found that, although the treatment started on day 0 was effective on viral load reduction, it provided no benefit when begun on day 3, indicating that in vivo antiviral efficacy becomes less prominent once viremia reaches the peak level. To determine if the therapeutic regimen in humans could be improved, we tested regimen of four-times daily treatment and found that the treatment significantly reduced viremia, suggesting that a similar regimen may be effective in a human clinical trial. A new clinical trial to investigate an altered dosing regimen has been approved (NCT02569827). Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Pathogenesis of Dengue Vaccine Viruses in Mosquitoes.

    Science.gov (United States)

    1980-01-01

    1973). Sabin (1948) showed that attenuated dpngiie, passed through mosquitoes, did not revert to pathogenicity frnr man. -7- Thus even if the vaccine ...AD-A138 518 PATHOGENESIS OF DENGUE VACCINE YIRUSES IN MOSQUITOES 1/ (U) YALE UNIV NEW HAVEN CONN SCHOOL OF MEDICINE B J BEATY ET AL. 9i JAN 80 DRND7...34 ’ UNCLASSIFIED 0{) AD 0Pathogenesis of dengue vaccine viruses in mosquitoes -First Annual Report Barry I. Beaty, Ph.D. Thomas H. G

  15. TRANSMISI TRANSOVARIAL VIRUS DENGUE PADA TELUR NYAMUK AEDES AEGYPTI(L.

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    Magdalena Desiree Seran

    2013-03-01

    Full Text Available Abstract. The ability of dengue virus to maintain its existence in nature through two mechanisms, both horizontal and vertical transmission (transovarial of the infective female mosquitoes to the next generation. This study aims to investigate the transovarial transmission and transovarial infection rate (TIR of dengue virus in eggs Aedes aegypti infected mother has a peroral virus DEN-2. This study is an experimental study in the laboratory. The population of the study was Ae. aegypti adults who have previously been infected with DEN-2 virus orally and proved to be infected with DEN-2 transovarially (Fl. The research sample was egg of Ae. aegypti from F2 generation which colonized from DEN-2 transovarially infected Ae. aegypti (Fl. Egg squash preparations made as many as 50 samples from jive difJerent mosquito parents. The presence of dengue virus antigen in mosquitoes FO and Fl were checked by SPBC immunocytochemistry method and using monoclonal antibodies DSSC7 (l: 50 as standardized primary antibodies. The results shows the existence of transovarial transmission of dengue virus in eggs Ae. aegypti (F2 were seen in squash preparations in the form of a brownish color egg spread on embryonic tissues (TIR= 52%. It concludes that dengue virus is able to be transmitted vertically through the egg. Keywords: transovarial transmission, eggsquash, Aedes aegypti, transovarial infection rate (TIR Abstrak. Kemampuan virus dengue untuk mempertahankan keberadaanya di alam dilakukan melalui dua mekanisme yaitu transmisi horizontal dan dengan transmisi vertikal (transovarial yaitu dari nyamuk betina infektif ke generasi berikutnya. Penelitian ini bertujuan untuk mengetahui adanya transmisi transovarial dan transovarial infection rate (TIR virus dengue pada telur Ae. aegypti yang induknya telah diinfeksi virus DEN-2 secara peroraI. Penelitian merupakan jenis penelitian eksperimental di laboratorium. Populasi penelitian adalah Ae. aegypti betina dewasa yang

  16. Dynamics of Dengue Virus (DENV)–Specific B Cells in the Response to DENV Serotype 1 Infections, Using Flow Cytometry With Labeled Virions

    Science.gov (United States)

    Woda, Marcia; Friberg, Heather; Currier, Jeffrey R.; Srikiatkhachorn, Anon; Macareo, Louis R.; Green, Sharone; Jarman, Richard G.; Rothman, Alan L.; Mathew, Anuja

    2016-01-01

    Background. The development of reagents to identify and characterize antigen-specific B cells has been challenging. Methods. We recently developed Alexa Fluor–labeled dengue viruses (AF DENVs) to characterize antigen-specific B cells in the peripheral blood of DENV-immune individuals. Results. In this study, we used AF DENV serotype 1 (AF DENV-1) together with AF DENV-2 on peripheral blood mononuclear cells (PBMCs) from children in Thailand with acute primary or secondary DENV-1 infections to analyze the phenotypes of antigen-specific B cells that reflected their exposure or clinical diagnosis. DENV serotype-specific and cross-reactive B cells were identified in PBMCs from all subjects. Frequencies of AF DENV+ class-switched memory B cells (IgD−CD27+ CD19+ cells) reached up to 8% during acute infection and early convalescence. AF DENV–labeled B cells expressed high levels of CD27 and CD38 during acute infection, characteristic of plasmablasts, and transitioned into memory B cells (CD38−CD27+) at the early convalescent time point. There was higher activation of memory B cells early during acute secondary infection, suggesting reactivation from a previous DENV infection. Conclusions. AF DENVs reveal changes in the phenotype of DENV serotype–specific and cross-reactive B cells during and after natural DENV infection and could be useful in analysis of the response to DENV vaccination. PMID:27443614

  17. Immunopathogenesis of Dengue Virus-Induced Redundant Cell Death: Apoptosis and Pyroptosis.

    Science.gov (United States)

    Suwanmanee, San; Luplertlop, Natthanej

    Dengue virus infection is a self-limited condition, which is of particular importance in tropical and subtropical regions and for which no specific treatment or effective vaccine is available. There are several hypotheses explaining dengue pathogenesis. These usually refer to host immune responses, including antibody-dependent enhancement, cytokine expression, and dengue virus particles including NS1 protein, which lead to cell death by both apoptosis and pyroptosis. A clear understanding of the pathogenesis should facilitate the development of vaccines and therapies. This review focuses on the immunopathogenesis in relation to clinical manifestations and patterns of cell death, focusing on the pathogenesis of severe dengue.

  18. Interferon lambda inhibits dengue virus replication in epithelial cells.

    Science.gov (United States)

    Palma-Ocampo, Helen K; Flores-Alonso, Juan C; Vallejo-Ruiz, Verónica; Reyes-Leyva, Julio; Flores-Mendoza, Lilian; Herrera-Camacho, Irma; Rosas-Murrieta, Nora H; Santos-López, Gerardo

    2015-09-28

    In viral disease, infection is controlled at the cellular level by type I interferon (IFN-I), but dengue virus (DENV) has the ability to inhibit this response. Type III interferon, also known as lambda IFN (IFN-III or IFN-λ), is a complementary pathway to the antiviral response by IFN-I. This work analyzed the IFN-λ (IFN-III) mediated antiviral response against DENV serotype 2 (DENV-2) infection. Dengue fever patients were sampled to determine their IFN-λ levels by ELISA. To study the IFN-λ response during DENV infection we selected the epithelial cell line C33-A, and we demonstrated that it is permissive to DENV-2 infection. The effect of IFN-λ on virus replication was determined in these cells, in parallel to the expression of IFN-stimulated genes (ISGs), and Suppressor of Cytokine Signaling (SOCS), genes measured by RT-qPCR. We found increased (~1.8 times) serological IFN-λ in dengue fever patients compared to healthy blood donors. IFN-λ inhibited DENV-2 replication in a dose-dependent manner in vitro. The reduction of viral titer corresponded with increased ISG mRNA levels (MX1 and OAS1), with the highest inhibition occurring at ISG's peak expression. Presence of IFN-negative regulators, SOCS1 and SOCS3, during DENV-2 infection was associated with reduced IFN-λ1 expression. Evidence described here suggests that IFN-λ is a good candidate inhibitor of viral replication in dengue infection. Mechanisms for the cellular and organismal interplay between DENV and IFN- λ need to be further studied as they could provide insights into strategies to treat this disease. Furthermore, we report a novel epithelial model to study dengue infection in vitro.

  19. Dengue-2 and yellow fever 17DD viruses infect human dendritic cells, resulting in an induction of activation markers, cytokines and chemokines and secretion of different TNF-α and IFN-α profiles

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    Mariana Gandini

    2011-08-01

    Full Text Available Flaviviruses cause severe acute febrile and haemorrhagic infections, including dengue and yellow fever and the pathogenesis of these infections is caused by an exacerbated immune response. Dendritic cells (DCs are targets for dengue virus (DENV and yellow fever virus (YF replication and are the first cell population to interact with these viruses during a natural infection, which leads to an induction of protective immunity in humans. We studied the infectivity of DENV2 (strain 16681, a YF vaccine (YF17DD and a chimeric YF17D/DENV2 vaccine in monocyte-derived DCs in vitro with regard to cell maturation, activation and cytokine production. Higher viral antigen positive cell frequencies were observed for DENV2 when compared with both vaccine viruses. Flavivirus-infected cultures exhibited dendritic cell activation and maturation molecules. CD38 expression on DCs was enhanced for both DENV2 and YF17DD, whereas OX40L expression was decreased as compared to mock-stimulated cells, suggesting that a T helper 1 profile is favoured. Tumor necrosis factor (TNF-α production in cell cultures was significantly higher in DENV2-infected cultures than in cultures infected with YF17DD or YF17D/DENV. In contrast, the vaccines induced higher IFN-α levels than DENV2. The differential cytokine production indicates that DENV2 results in TNF induction, which discriminates it from vaccine viruses that preferentially stimulate interferon expression. These differential response profiles may influence the pathogenic infection outcome.

  20. Dengue virus in blood donations, Puerto Rico, 2005.

    Science.gov (United States)

    Mohammed, Hamish; Linnen, Jeffrey M; Muñoz-Jordán, Jorge L; Tomashek, Kay; Foster, Gregory; Broulik, Amy S; Petersen, Lyle; Stramer, Susan L

    2008-07-01

    A single instance of transfusion-transmitted dengue infection has been reported. The high incidence of dengue in endemic countries, the high proportion of asymptomatic infection, and the median 5-day viremia, however, suggest that transfusion-associated dengue transmission may be more widespread than documented. The prevalence of dengue virus (DENV) RNA was determined in all blood donations to the American Red Cross in Puerto Rico from September 20 to December 4, 2005, using a specific type of nucleic acid amplification test called transcription-mediated amplification (TMA). TMA-positive donations were defined as those having two repeatedly reactive TMA results. TMA-positive donations were tested by enzyme-linked immunosorbent assay for immunoglobulin M (IgM) antibodies, by reverse transcription-polymerase chain reaction (RT-PCR), and by viral culture. Twelve (0.07%) of 16,521 blood donations tested were TMA-positive. Four were positive by RT-PCR (DENV serotypes 2 and 3). Virus was cultured from 3 of 4 RT-PCR-positive donations. One of the 12 TMA-positive donations was IgM-positive. Only 5 donations remained TMA-positive when diluted 1:16, as is done for routine minipool screening for other transfusion-transmissible viral infections (hepatitis C, human immunodeficiency, West Nile viruses [WNVs]). Nearly 1 in 1000 blood donations contained DENV RNA, and virus could be cultured from TMA-positive donations, suggesting a transfusion transmission risk similar to that which existed in the United States for WNV before universal donation screening. Similar to WNV, IgM antibody screening is likely to be ineffective, and some potentially infectious donations will be missed by minipool screening. Transfusion transmission should be considered in patients with dengue after blood transfusion.

  1. Surge of Dengue Virus Infection and Chikungunya Fever in Bali in 2010: The Burden of Mosquito-Borne Infectious Diseases in a Tourist Destination

    Science.gov (United States)

    Yoshikawa, Minako Jen; Kusriastuti, Rita

    2013-01-01

    Labor flow and travelers are important factors contributing to the spread of Dengue virus infection and chikungunya fever. Bali Province of Indonesia, a popular resort and tourist destination, has these factors and suffers from mosquito-borne infectious diseases. Using area study approach, a series of fieldwork was conducted in Bali to obtain up-to-date primary disease data, to learn more about public health measures, and to interview health officers, hotel personnel, and other resource persons. The national data including information on two other provinces were obtained for comparison. The health ministry reported 5,810 and 11,697 cases of dengue hemorrhagic fever in Bali in 2009 and 2010, respectively. Moreover, two densely populated tourist areas and one district have shown a particularly high incidence and sharp increases in 2010. Cases of chikungunya fever reported in Bali more than doubled in 2010 from the previous year. Our findings suggest that Bali can benefit from a significant reduction in vector populations and dissemination of disease preventive knowledge among both local residents and foreign visitors. This will require a concerted and trans-border approach, which may prove difficult in the province. PMID:23874141

  2. Antibody Recognition of the Dengue Virus Proteome and Implications for Development of Vaccines

    Science.gov (United States)

    2011-04-01

    Parvovirus B19 empty capsids as antigen carriers for presentation of antigenic detenninants of dengue 2 virus. J. Infect. Dis. 194:790-794. 3... reactiv - ity against other DENV serotypes (1, 35). In contrast to DF, dengue hemorrhagic fever (DHF) is an infrequent but far more serious consequence of...recipients of the tetrava- lent DENV vaccine or from dengue cases owing to antibody cross- reactivity among serotypes (29). Furthermore, as results from

  3. An outbreak of dengue virus (DENV) type 2 Cosmopolitan genotype in Israeli travellers returning from the Seychelles, April 2017.

    Science.gov (United States)

    Lustig, Yaniv; Wolf, Dana; Halutz, Ora; Schwartz, Eli

    2017-06-29

    Dengue virus infection was diagnosed in six Israeli travellers returning from the Seychelles in April 2017. Phylogenetic analysis identified identical sequences belonging to the Cosmopolitan genotype of dengue virus type 2 in all samples sequenced, thus providing evidence for a probable dengue type 2 outbreak in the Seychelles. This report further demonstrates the role of travellers as sentinels for arboviral infections, especially in countries with limited diagnostic capabilities. This article is copyright of The Authors, 2017.

  4. Identification and characterization of a virus-specific continuous B-cell epitope on the PrM/M protein of Japanese Encephalitis Virus: potential application in the detection of antibodies to distinguish Japanese Encephalitis Virus infection from West Nile Virus and Dengue Virus infections

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    Liu Wen-Xin

    2010-09-01

    Full Text Available Abstract Background Differential diagnose of Japanese encephalitis virus (JEV infection from other flavivirus especially West Nile virus (WNV and Dengue virus (DV infection was greatly hindered for the serological cross-reactive. Virus specific epitopes could benefit for developing JEV specific antibodies detection methods. To identify the JEV specific epitopes, we fully mapped and characterized the continuous B-cell epitope of the PrM/M protein of JEV. Results To map the epitopes on the PrM/M protein, we designed a set of 20 partially overlapping fragments spanning the whole PrM, fused them with GST, and expressed them in an expression vector. Linear epitope M14 (105VNKKEAWLDSTKATRY120 was detected by enzyme-linked immunosorbent assay (ELISA. By removing amino acid residues individually from the carboxy and amino terminal of peptide M14, we confirmed that the minimal unit of the linear epitope of PrM/M was M14-13 (108KEAWLDSTKAT118. This epitope was highly conserved across different JEV strains. Moreover, this epitope did not cross-react with WNV-positive and DENV-positive sera. Conclusion Epitope M14-13 was a JEV specific lineal B-cell epitpe. The results may provide a useful basis for the development of epitope-based virus specific diagnostic clinical techniques.

  5. Molecular surveillance of dengue in Semarang, Indonesia revealed the circulation of an old genotype of dengue virus serotype-1.

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    Sukmal Fahri

    Full Text Available Dengue disease is currently a major health problem in Indonesia and affects all provinces in the country, including Semarang Municipality, Central Java province. While dengue is endemic in this region, only limited data on the disease epidemiology is available. To understand the dynamics of dengue in Semarang, we conducted clinical, virological, and demographical surveillance of dengue in Semarang and its surrounding regions in 2012. Dengue cases were detected in both urban and rural areas located in various geographical features, including the coastal and highland areas. During an eight months' study, a total of 120 febrile patients were recruited, of which 66 were serologically confirmed for dengue infection using IgG/IgM ELISA and/or NS1 tests. The cases occurred both in dry and wet seasons. Majority of patients were under 10 years old. Most patients were diagnosed as dengue hemorrhagic fever, followed by dengue shock syndrome and dengue fever. Serotyping was performed in 31 patients, and we observed the co-circulation of all four dengue virus (DENV serotypes. When the serotypes were correlated with the severity of the disease, no direct correlation was observed. Phylogenetic analysis of DENV based on Envelope gene sequence revealed the circulation of DENV-2 Cosmopolitan genotype and DENV-3 Genotype I. A striking finding was observed for DENV-1, in which we found the co-circulation of Genotype I with an old Genotype II. The Genotype II was represented by a virus strain that has a very slow mutation rate and is very closely related to the DENV strain from Thailand, isolated in 1964 and never reported in other countries in the last three decades. Moreover, this virus was discovered in a cool highland area with an elevation of 1,001 meters above the sea level. The discovery of this old DENV strain may suggest the silent circulation of old virus strains in Indonesia.

  6. Current management of severe dengue infection.

    Science.gov (United States)

    Lee, Tau Hong; Lee, Linda Kay; Lye, David Chien; Leo, Yee Sin

    2017-01-01

    Traditionally a disease mainly affecting the pediatric population, dengue burden has increased significantly in recent decades and adults with severe disease may become more common. There is currently no effective anti-viral agent available for the treatment of dengue and supportive care is the mainstay of management. Areas covered: We present a review of current literature on dengue severity classification systems and the management of severe dengue in adults. In particular, emphasis was placed on organ impairment in dengue and management of elderly individuals with multiple medical problems. Expert commentary: There is an urgent need to search for an effective anti-viral agent to treat infected individuals. The commercial availability of a dengue vaccine in older children has provided optimism in reducing the disease burden but long term efficacy and safety are unknown. The results from phase III trials of two new candidate vaccines are eagerly awaited.

  7. First evidence of dengue infection in domestic dogs living in different ecological settings in Thailand.

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    Suporn Thongyuan

    Full Text Available Dengue is a vector-borne disease transmitted by Aedes mosquitoes. It is considered an important public health problem in many countries worldwide. However, only a few studies have been conducted on primates and domestic animals that could potentially be a reservoir of dengue viruses. Since domestic dogs share both habitats and vectors with humans, this study aimed to investigate whether domestic dogs living in different ecological settings in dengue endemic areas in Thailand could be naturally infected with dengue viruses.Serum samples were collected from domestic dogs in three different ecological settings of Thailand: urban dengue endemic areas of Nakhon Sawan Province; rubber plantation areas of Rayong Province; and Koh Chang, an island tourist spot of Trat Province. These samples were screened for dengue viral genome by using semi-nested RT-PCR. Positive samples were then inoculated in mosquito and dog cell lines for virus isolation. Supernatant collected from cell culture was tested for the presence of dengue viral genome by semi-nested RT-PCR, then double-strand DNA products were double-pass custom-sequenced. Partial nucleotide sequences were aligned with the sequences already recorded in GenBank, and a phylogenetic tree was constructed. In the urban setting, 632 domestic dog serum samples were screened for dengue virus genome by RT-PCR, and six samples (0.95% tested positive for dengue virus. Four out of six dengue viruses from positive samples were successfully isolated. Dengue virus serotype 2 and serotype 3 were found to have circulated in domestic dog populations. One of 153 samples (0.65% collected from the rubber plantation area showed a PCR-positive result, and dengue serotype 3 was successfully isolated. Partial gene phylogeny revealed that the isolated dengue viruses were closely related to those strains circulating in human populations. None of the 71 samples collected from the island tourist spot showed a positive result

  8. Knowledge, attitude, and practice regarding dengue virus infection among inhabitants of Aceh, Indonesia: a cross-sectional study.

    Science.gov (United States)

    Harapan, Harapan; Rajamoorthy, Yogambigai; Anwar, Samsul; Bustamam, Aslam; Radiansyah, Arsil; Angraini, Pradiba; Fasli, Riny; Salwiyadi, Salwiyadi; Bastian, Reza Akbar; Oktiviyari, Ade; Akmal, Imaduddin; Iqbalamin, Muhammad; Adil, Jamalul; Henrizal, Fenni; Darmayanti, Darmayanti; Pratama, Rovy; Setiawan, Abdul Malik; Mudatsir, Mudatsir; Hadisoemarto, Panji Fortuna; Dhimal, Mandira Lamichhane; Kuch, Ulrich; Groneberg, David Alexander; Imrie, Allison; Dhimal, Meghnath; Müller, Ruth

    2018-02-27

    The Indonesian region of Aceh was the area most severely affected by the earthquake and tsunami of 26 December 2004. Department of Health data reveal an upward trend of dengue cases in Aceh since the events of the tsunami. Despite the increasing incidence of dengue in the region, there is limited understanding of dengue among the general population of Aceh. The aim of this study was to assess the knowledge, attitude, and practice (KAP) regarding dengue among the people of Aceh, Indonesia in order to design intervention strategies for an effective dengue prevention program. A community-based cross-sectional study was conducted in Aceh between November 2014 and March 2015 with a total of 609 participants living in seven regencies and two municipalities. Information on the socio-demographic characteristics of participants and their KAP regarding dengue was collected using a pre-tested structured questionnaire. The KAP status (good vs. poor) of participants with different socio-demographic characteristics was compared using Chi Square-test, ANOVA or Fisher's exact test as appropriate. Logistic regression analysis was used to determine the predictors of each KAP domain. We found that 45% of participants had good knowledge regarding dengue and only 32% had good attitudes and good dengue preventive practices. There was a significant positive correlation between knowledge and attitudes, knowledge and practice, and attitudes and practice. In addition, people who had good knowledge were 2.7 times more likely to have good attitudes, and people who had good attitudes were 2.2 times more likely to have good practices regarding dengue. The level of education, occupation, marital status, monthly income, socioeconomic status (SES) and living in the city were associated with the knowledge level. Occupation, SES, and having experienced dengue fever were associated with attitudes. Education, occupation, SES and type of residence were associated with preventive practices. Our study

  9. Identification of human hnRNP C1/C2 as a dengue virus NS1-interacting protein

    International Nuclear Information System (INIS)

    Noisakran, Sansanee; Sengsai, Suchada; Thongboonkerd, Visith; Kanlaya, Rattiyaporn; Sinchaikul, Supachok; Chen, Shui-Tein; Puttikhunt, Chunya

    2008-01-01

    Dengue virus nonstructural protein 1 (NS1) is a key glycoprotein involved in the production of infectious virus and the pathogenesis of dengue diseases. Very little is known how NS1 interacts with host cellular proteins and functions in dengue virus-infected cells. This study aimed at identifying NS1-interacting host cellular proteins in dengue virus-infected cells by employing co-immunoprecipitation, two-dimensional gel electrophoresis, and mass spectrometry. Using lysates of dengue virus-infected human embryonic kidney cells (HEK 293T), immunoprecipitation with an anti-NS1 monoclonal antibody revealed eight isoforms of dengue virus NS1 and a 40-kDa protein, which was subsequently identified by quadrupole time-of-flight tandem mass spectrometry (Q-TOF MS/MS) as human heterogeneous nuclear ribonucleoprotein (hnRNP) C1/C2. Further investigation by co-immunoprecipitation and co-localization confirmed the association of hnRNP C1/C2 and dengue virus NS1 proteins in dengue virus-infected cells. Their interaction may have implications in virus replication and/or cellular responses favorable to survival of the virus in host cells

  10. Complement-mediated neutralization of dengue virus requires mannose-binding lectin

    DEFF Research Database (Denmark)

    Avirutnan, Panisadee; Hauhart, Richard E; Marovich, Mary A

    2011-01-01

    -dependent activation of the complement cascade neutralized insect cell-derived West Nile virus (WNV) in cell culture and restricted pathogenesis in mice. Here, we investigated the antiviral activity of MBL in infection by dengue virus (DENV), a related flavivirus. Using a panel of naïve sera from mouse strains...... with lower levels. Our studies suggest that allelic variation of MBL in humans may impact complement-dependent control of DENV pathogenesis. IMPORTANCE Dengue virus (DENV) is a mosquito-transmitted virus that causes a spectrum of clinical disease in humans ranging from subclinical infection to dengue...... hemorrhagic fever and dengue shock syndrome. Four serotypes of DENV exist, and severe illness is usually associated with secondary infection by a different serotype. Here, we show that mannose-binding lectin (MBL), a pattern recognition molecule that initiates the lectin pathway of complement activation...

  11. Induction of a peptide with activity against a broad spectrum of pathogens in the Aedes aegypti salivary gland, following Infection with Dengue Virus.

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    Natthanej Luplertlop

    2011-01-01

    Full Text Available The ultimate stage of the transmission of Dengue Virus (DENV to man is strongly dependent on crosstalk between the virus and the immune system of its vector Aedes aegypti (Ae. aegypti. Infection of the mosquito's salivary glands by DENV is the final step prior to viral transmission. Therefore, in the present study, we have determined the modulatory effects of DENV infection on the immune response in this organ by carrying out a functional genomic analysis of uninfected salivary glands and salivary glands of female Ae. aegypti mosquitoes infected with DENV. We have shown that DENV infection of salivary glands strongly up-regulates the expression of genes that encode proteins involved in the vector's innate immune response, including the immune deficiency (IMD and Toll signalling pathways, and that it induces the expression of the gene encoding a putative anti-bacterial, cecropin-like, peptide (AAEL000598. Both the chemically synthesized non-cleaved, signal peptide-containing gene product of AAEL000598, and the cleaved, mature form, were found to exert, in addition to antibacterial activity, anti-DENV and anti-Chikungunya viral activity. However, in contrast to the mature form, the immature cecropin peptide was far more effective against Chikungunya virus (CHIKV and, furthermore, had strong anti-parasite activity as shown by its ability to kill Leishmania spp. Results from circular dichroism analysis showed that the immature form more readily adopts a helical conformation which would help it to cause membrane permeabilization, thus permitting its transfer across hydrophobic cell surfaces, which may explain the difference in the anti-pathogenic activity between the two forms. The present study underscores not only the importance of DENV-induced cecropin in the innate immune response of Ae. aegypti, but also emphasizes the broad-spectrum anti-pathogenic activity of the immature, signal peptide-containing form of this peptide.

  12. Dengue Virus 1 Outbreak in Buenos Aires, Argentina, 2016.

    Science.gov (United States)

    Tittarelli, Estefanía; Lusso, Silvina B; Goya, Stephanie; Rojo, Gabriel L; Natale, Mónica I; Viegas, Mariana; Mistchenko, Alicia S; Valinotto, Laura E

    2017-10-01

    The largest outbreak of dengue in Buenos Aires, Argentina, occurred during 2016. Phylogenetic, phylodynamic, and phylogeographic analyses of 82 samples from dengue patients revealed co-circulation of 2 genotype V dengue virus lineages, suggesting that this virus has become endemic to the Buenos Aires metropolitan area.

  13. Oral receptivity of Aedes aegypti from Cape Verde for yellow fever, dengue, and chikungunya viruses.

    Science.gov (United States)

    Vazeille, Marie; Yébakima, André; Lourenço-de-Oliveira, Ricardo; Andriamahefazafy, Barrysson; Correira, Artur; Rodrigues, Julio Monteiro; Veiga, Antonio; Moreira, Antonio; Leparc-Goffart, Isabelle; Grandadam, Marc; Failloux, Anna-Bella

    2013-01-01

    At the end of 2009, 21,313 cases of dengue-3 virus (DENV-3) were reported in the islands of Cape Verde, an archipelago located in the Atlantic Ocean 570 km from the coast of western Africa. It was the first dengue outbreak ever reported in Cape Verde. Mosquitoes collected in July 2010 in the city of Praia, on the island of Santiago, were identified morphologically as Aedes aegypti formosus. Using experimental oral infections, we found that this vector showed a moderate ability to transmit the epidemic dengue-3 virus, but was highly susceptible to chikungunya and yellow fever viruses.

  14. Transmission potential of Zika virus infection in the South Pacific

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    Hiroshi Nishiura

    2016-04-01

    Conclusions: The transmissibility of Zika virus infection appears to be comparable to those of dengue and chikungunya viruses. Considering that Aedes species are a shared vector, this finding indicates that Zika virus replication within the vector is perhaps comparable to dengue and chikungunya.

  15. Lovastatin delays infection and increases survival rates in AG129 mice infected with dengue virus serotype 2.

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    Marlen Martinez-Gutierrez

    Full Text Available BACKGROUND: It has been reported that treatment of DENV-infected cultures with Lovastatin (LOV, can affect viral assembly. The objective of this study was to evaluate the effect of LOV on the survival rate and viremia levels of DENV-2-infected AG129 mice. METHODOLOGY/PRINCIPAL FINDINGS: Mice were inoculated with 1 × 10(6 plaque-forming units (PFU/ml of DENV-2 and treated with LOV (200 mg/kg/day. Pre-treatment with one or three doses of LOV increased the survival rate compared to untreated mice (7.3 and 7.1 days, respectively, compared to 4.8 days. Viremia levels also decreased by 21.8% compared to untreated mice, but only in the group administered three doses prior to inoculation. When LOV was administered after viral inoculation, the survival rate increased (7.3 days in the group treated at 24 hpi, 6.8 days in the group treated at 48 hpi and 6.5 days in the group treated with two doses compared to the untreated group (4.8 days. Interestingly, the serum viral titer increased by 24.6% in mice treated at 48 hpi with a single dose of LOV and by 21.7% in mice treated with two doses (at 24 and 48 hpi of LOV compared to untreated mice. Finally histopathological changes in the liver and spleen in infected and untreated mice included massive extramedullary erythropoiesis foci and inflammatory filtration, and these characteristics were decreased or absent in LOV-treated mice. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the effect of LOV on viremia depends on the timing of treatment and on the number of doses administered. We observed a significant increase in the survival rate in both schemes due to a delay in the progression of the disease. However, the results obtained in the post-treatment scheme must be handled carefully because this treatment scheme increases viremia and we do not know how this increase could affect disease progression in humans.

  16. Sulfated polysaccharide, curdlan sulfate, efficiently prevents entry/fusion and restricts antibody-dependent enhancement of dengue virus infection in vitro: a possible candidate for clinical application.

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    Koji Ichiyama

    Full Text Available Curdlan sulfate (CRDS, a sulfated 1→3-β-D glucan, previously shown to be a potent HIV entry inhibitor, is characterized in this study as a potent inhibitor of the Dengue virus (DENV. CRDS was identified by in silico blind docking studies to exhibit binding potential to the envelope (E protein of the DENV. CRDS was shown to inhibit the DENV replication very efficiently in different cells in vitro. Minimal effective concentration of CRDS was as low as 0.1 µg/mL in LLC-MK2 cells, and toxicity was observed only at concentrations over 10 mg/mL. CRDS can also inhibit DENV-1, 3, and 4 efficiently. CRDS did not inhibit the replication of DENV subgenomic replicon. Time of addition experiments demonstrated that the compound not only inhibited viral infection at the host cell binding step, but also at an early post-attachment step of entry (membrane fusion. The direct binding of CRDS to DENV was suggested by an evident reduction in the viral titers after interaction of the virus with CRDS following an ultrafiltration device separation, as well as after virus adsorption to an alkyl CRDS-coated membrane filter. The electron microscopic features also showed that CRDS interacted directly with the viral envelope, and caused changes to the viral surface. CRDS also potently inhibited DENV infection in DC-SIGN expressing cells as well as the antibody-dependent enhancement of DENV-2 infection. Based on these data, a probable binding model of CRDS to DENV E protein was constructed by a flexible receptor and ligand docking study. The binding site of CRDS was predicted to be at the interface between domains II and III of E protein dimer, which is unique to this compound, and is apparently different from the β-OG binding site. Since CRDS has already been tested in humans without serious side effects, its clinical application can be considered.

  17. Ficus septica plant extracts for treating Dengue virus in vitro

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    Nan-Chieh Huang

    2017-06-01

    Full Text Available Dengue virus types 1-4 (DENV-1-4 are positive-strand RNA viruses with an envelope that belongs to the Flaviviridae. DENV infection threatens human health worldwide. However, other than supportive treatments, no specific therapy is available for the infection. In order to discover novel medicine against DENV, we tested 59 crude extracts, without cytotoxicity, from 23 plants in vitro; immunofluorescence assay revealed that the methanol extracts of fruit, heartwood, leaves and stem from Ficus septica Burm. f. had a promising anti-DENV-1 and DENV-2 effect. However, infection with the non-envelope picornavirus, Aichi virus, was not inhibited by treatment with F. septica extracts. F. septica may be a candidate antiviral drug against an enveloped virus such as DENV.

  18. PERK Signal-Modulated Protein Translation Promotes the Survivability of Dengue 2 Virus-Infected Mosquito Cells and Extends Viral Replication.

    Science.gov (United States)

    Hou, Jiun-Nan; Chen, Tien-Huang; Chiang, Yi-Hsuan; Peng, Jing-Yun; Yang, Tsong-Han; Cheng, Chih-Chieh; Sofiyatun, Eny; Chiu, Cheng-Hsun; Chiang-Ni, Chuan; Chen, Wei-June

    2017-09-20

    Survival of mosquitoes from dengue virus (DENV) infection is a prerequisite of viral transmission to the host. This study aimed to see how mosquito cells can survive the infection during prosperous replication of the virus. In C6/36 cells, global protein translation was shut down after infection by DENV type 2 (DENV2). However, it returned to a normal level when infected cells were treated with an inhibitor of the protein kinase RNA (PKR)-like ER kinase (PERK) signaling pathway. Based on a 7-Methylguanosine 5'-triphosphate (m7GTP) pull-down assay, the eukaryotic translation initiation factor 4F (eIF4F) complex was also identified in DENV2-infected cells. This suggests that most mosquito proteins are synthesized via canonical cap-dependent translation. When the PERK signal pathway was inhibited, both accumulation of reactive oxygen species and changes in the mitochondrial membrane potential increased. This suggested that ER stress response was alleviated through the PERK-mediated shutdown of global proteins in DENV2-infected C6/36 cells. In the meantime, the activities of caspases-9 and -3 and the apoptosis-related cell death rate increased in C6/36 cells with PERK inhibition. This reflected that the PERK-signaling pathway is involved in determining cell survival, presumably by reducing DENV2-induced ER stress. Looking at the PERK downstream target, α-subunit of eukaryotic initiation factor 2 (eIF2α), an increased phosphorylation status was only shown in infected C6/36 cells. This indicated that recruitment of ribosome binding to the mRNA 5'-cap structure could have been impaired in cap-dependent translation. It turned out that shutdown of cellular protein translation resulted in a pro-survival effect on mosquito cells in response to DENV2 infection. As synthesis of viral proteins was not affected by the PERK signal pathway, an alternate mode other than cap-dependent translation may be utilized. This finding provides insights into elucidating how the PERK signal

  19. Anti-GBM disease and ANCA during dengue infection.

    Science.gov (United States)

    Lizarraga, Karlo J; Florindez, Jorge A; Daftarian, Pirouz; Andrews, David M; Ortega, Luis M; Mendoza, Jair Munoz; Contreras, Gabriel N; Nayer, Ali

    2015-02-01

    Anti-glomerular basement membrane (GBM) disease is a severe inflammatory renal disorder due to pathogenic autoantibodies directed mainly against the α3 chain of type IV collagen. In ~1/4 of patients with anti-GBM disease, antineutrophil cytoplasmic antibodies (ANCA) predominantly with myeloperoxidase (MPO) specificity can be detected. Although the inciting stimuli leading to the development of an immune response against the type IV collagen and neutrophils are unknown, evidence indicates that both genetic and environmental factors play a role. Of note, molecular mimicry between self-antigens and nonself-antigens such as antigenic determinants of microorganisms has been implicated in the pathogenesis of anti-GBM disease and ANCA-associated vasculitis. A mosquito-borne viral illness highly prevalent in the tropics and subtropics, dengue can be complicated by acute renal failure, proteinuria, hematuria and glomerulonephritis. We present a 66-year-old woman who was diagnosed with dengue infection and rapidly progressive glomerulonephritis during an outbreak of dengue in Honduras in the summer of 2013. Renal biopsy revealed severe crescentic glomerulonephritis. Immunofluorescence examination demonstrated strong linear IgG deposition along glomerular capillary walls. Serologic tests demonstrated antibodies against GBM, MPO and platelet glycoproteins. The patient was diagnosed with anti-GBM disease associated with p-ANCA with MPO specificity. Despite heavy immunosuppression and plasmapheresis, IgG titers against dengue virus continued to rise confirming the diagnosis of acute dengue infection. We present the first reported case of anti-GBM disease associated with p-ANCA with MPO specificity during dengue infection. This report calls for a heightened awareness of autoimmunity leading to crescentic glomerulonephritis in patients with dengue infection.

  20. Virus del dengue: estructura y ciclo viral Dengue virus: structure and viral cycle

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    Myriam L Velandia

    2011-03-01

    Full Text Available El virus del dengue (DENV es el agente causal de la enfermedad conocida como dengue, que es la principal enfermedad viral transmitida por artrópodos en el mundo. El DENV es un flavivirus que ingresa por endocitosis y se replica en el citoplasma de la célula infectada, originando tres proteínas estructurales y siete proteínas no estructurales, sobre las cuales se conocen sólo algunas de sus funciones en la replicación viral o en la infección. El ciclo viral que ocurre en las células infectadas hasta ahora está comenzando a aclararse y su conocimiento permitirá en el futuro próximo diseñar racionalmente moléculas que lo intervengan y eviten la replicación del virus. Durante la infección, el individuo puede presentar fiebre indiferenciada o, en otros casos, puede presentar un proceso generalizado de activación de la respuesta inmunitaria innata y adquirida, lo cual provoca la liberación de factores inflamatorios solubles que alteran la fisiología de los tejidos, principalmente el endotelio, conllevando al desarrollo de manifestaciones clínicas graves. Aunque se ha identificado un gran número de factores del individuo asociados al desarrollo de la enfermedad por DENV, queda por identificar el papel de las diferentes proteínas virales en la patogenia de la enfermedad. En la presente revisión, se presenta una breve actualización sobre la estructura y biología del DENV, de su ciclo viral intracelular y, finalmente, se introducen algunos conceptos sobre la inmunopatogenia de la enfermedad producida por este agente.Dengue virus (DENV is responsible for the clinical entity known as dengue that is a great concern for economy and public health of tropical countries. This flavivirus is a single strand RNA virus that after their translation and replication in host cells produces three structural and seven non-structural proteins with specific function in replication or cell binding process that we will describe here. Intracellular

  1. Individual co-variation between viral RNA load and gene expression reveals novel host factors during early dengue virus infection of the Aedes aegypti midgut.

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    Vincent Raquin

    2017-12-01

    Full Text Available Dengue virus (DENV causes more human infections than any other mosquito-borne virus. The current lack of antiviral strategies has prompted genome-wide screens for host genes that are required for DENV infectivity. Earlier transcriptomic studies that identified DENV host factors in the primary vector Aedes aegypti used inbred laboratory colonies and/or pools of mosquitoes that erase individual variation. Here, we performed transcriptome sequencing on individual midguts in a field-derived Ae. aegypti population to identify new candidate host factors modulating DENV replication. We analyzed the transcriptomic data using an approach that accounts for individual co-variation between viral RNA load and gene expression. This approach generates a prediction about the agonist or antagonist effect of candidate genes on DENV replication based on the sign of the correlation between gene expression and viral RNA load. Using this method, we identified 39 candidate genes that went undetected by conventional pairwise comparison of gene expression levels between DENV-infected midguts and uninfected controls. Only four candidate genes were detected by both methods, emphasizing their complementarity. We demonstrated the value of our approach by functional validation of a candidate agonist gene encoding a sterol regulatory element-binding protein (SREBP, which was identified by correlation analysis but not by pairwise comparison. We confirmed that SREBP promotes DENV infection in the midgut by RNAi-mediated gene knockdown in vivo. We suggest that our approach for transcriptomic analysis can empower genome-wide screens for potential agonist or antagonist factors by leveraging inter-individual variation in gene expression. More generally, this method is applicable to a wide range of phenotypic traits displaying inter-individual variation.

  2. Successful treatment of thrombotic microangiopathy associated with dengue infection: A case report and literature review.

    Science.gov (United States)

    Nieto-Ríos, John Fredy; Álvarez Barreneche, María Fernanda; Penagos, Sara Catalina; Bello Márquez, Diana Carolina; Serna-Higuita, Lina Maria; Ramírez Sánchez, Isabel Cristina

    2018-02-01

    Dengue infection has been associated with multiple renal complications, including glomerulonephritis, acute tubular necrosis, tubulointerstitial nephritis, and thrombotic microangiopathy (TMA), this last one being a rare complication of dengue, with only a few reported cases. TMA associated with dengue can be explained by an alteration in the activity of the enzyme ADAMTS13, leading to thrombotic thrombocytopenic purpura; or it can be secondary to direct or indirect endothelial injury by the virus, which leads to hemolytic uremic syndrome. Here, we present a case of severe TMA, not related to ADAMTS13, which was clearly associated with dengue infection. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Dynamics of Dengue Virus (DENV)-Specific B Cells in the Response to DENV Serotype 1 Infections, Using Flow Cytometry With Labeled Virions.

    Science.gov (United States)

    Woda, Marcia; Friberg, Heather; Currier, Jeffrey R; Srikiatkhachorn, Anon; Macareo, Louis R; Green, Sharone; Jarman, Richard G; Rothman, Alan L; Mathew, Anuja

    2016-10-01

    The development of reagents to identify and characterize antigen-specific B cells has been challenging. We recently developed Alexa Fluor-labeled dengue viruses (AF DENVs) to characterize antigen-specific B cells in the peripheral blood of DENV-immune individuals. In this study, we used AF DENV serotype 1 (AF DENV-1) together with AF DENV-2 on peripheral blood mononuclear cells (PBMCs) from children in Thailand with acute primary or secondary DENV-1 infections to analyze the phenotypes of antigen-specific B cells that reflected their exposure or clinical diagnosis. DENV serotype-specific and cross-reactive B cells were identified in PBMCs from all subjects. Frequencies of AF DENV(+) class-switched memory B cells (IgD(-)CD27(+) CD19(+) cells) reached up to 8% during acute infection and early convalescence. AF DENV-labeled B cells expressed high levels of CD27 and CD38 during acute infection, characteristic of plasmablasts, and transitioned into memory B cells (CD38(-)CD27(+)) at the early convalescent time point. There was higher activation of memory B cells early during acute secondary infection, suggesting reactivation from a previous DENV infection. AF DENVs reveal changes in the phenotype of DENV serotype-specific and cross-reactive B cells during and after natural DENV infection and could be useful in analysis of the response to DENV vaccination. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  4. Dengue Infection in Children in Ratchaburi, Thailand: A Cohort Study. I. Epidemiology of Symptomatic Acute Dengue Infection in Children, 2006–2009

    Science.gov (United States)

    Sabchareon, Arunee; Sirivichayakul, Chukiat; Limkittikul, Kriengsak; Chanthavanich, Pornthep; Suvannadabba, Saravudh; Jiwariyavej, Vithaya; Dulyachai, Wut; Pengsaa, Krisana; Margolis, Harold S.; Letson, G. William

    2012-01-01

    Background There is an urgent need to field test dengue vaccines to determine their role in the control of the disease. Our aims were to study dengue epidemiology and prepare the site for a dengue vaccine efficacy trial. Methods and Findings We performed a prospective cohort study of children in primary schools in central Thailand from 2006 through 2009. We assessed the epidemiology of dengue by active fever surveillance for acute febrile illness as detected by school absenteeism and telephone contact of parents, and dengue diagnostic testing. Dengue accounted for 394 (6.74%) of the 5,842 febrile cases identified in 2882, 3104, 2717 and 2312 student person-years over the four years, respectively. Dengue incidence was 1.77% in 2006, 3.58% in 2007, 5.74% in 2008 and 3.29% in 2009. Mean dengue incidence over the 4 years was 3.6%. Dengue virus (DENV) types were determined in 333 (84.5%) of positive specimens; DENV serotype 1 (DENV-1) was the most common (43%), followed by DENV-2 (29%), DENV-3 (20%) and DENV-4 (8%). Disease severity ranged from dengue hemorrhagic fever (DHF) in 42 (10.5%) cases, dengue fever (DF) in 142 (35.5%) cases and undifferentiated fever (UF) in 210 (52.5%) cases. All four DENV serotypes were involved in all disease severity. A majority of cases had secondary DENV infection, 95% in DHF, 88.7% in DF and 81.9% in UF. Two DHF (0.5%) cases had primary DENV-3 infection. Conclusion The results illustrate the high incidence of dengue with all four DENV serotypes in primary school children, with approximately 50% of disease manifesting as mild clinical symptoms of UF, not meeting the 1997 WHO criteria for dengue. Severe disease (DHF) occurred in one tenth of cases. Data of this type are required for clinical trials to evaluate the efficacy of dengue vaccines in large scale clinical trials. PMID:22860141

  5. Serodiagnosis of dengue infection using rapid immunochromatography test in patients with probable dengue infection.

    Science.gov (United States)

    Kidwai, Aneela Altaf; Jamal, Qaiser; Saher; Mehrunnisa; Farooqi, Faiz-ur-rehman; Saleem-Ullah

    2010-11-01

    To determine the frequency of seropositive dengue infection using rapid immunochromatographic assay in patients with probable dengue infection as per WHO criteria. A cross-sectional observational study was conducted at Abbasi Shaheed Hospital, Karachi from July 2008 to January 2009. Patients presenting with acute febrile illness, rashes, bleeding tendencies, leucopenia and or thrombocytopenia were evaluated according to WHO criteria for probable dengue infection. Acute phase sera were collected after 5 days of the onset of fever as per WHO criteria. Serology was performed using rapid immunochromatographic (ICT) assay with differential detection of IgM and IgG. A primary dengue infection was defined by a positive IgM band and a negative IgG band whereas secondary infection was defined by a positive IgG band with or without positive IgM band. Among 599 patients who met the WHO criteria for dengue infection, 251(41.9%) were found to be ICT reactive among whom 42 (16.73%) had primary infection. Secondary infection was reported in 209 (83.26%). Acute phase sera of 348 (58.09%) were ICT non reactive. Four patients died because of dengue shock syndrome among which three had secondary infection. Early identification of secondary infection in acute phase sera using rapid ICT is valuable in terms of disease progression and mortality. However in highly suspected cases of dengue infection clinical management should not rely on negative serological results.

  6. Serodiagnosis of dengue infection using rapid immuno chromatography test in patients with probable dengue infection

    International Nuclear Information System (INIS)

    Kidwai, A.A.; Jamal, Q.; Mehrunnisa, S.; Farooqi, F.R.

    2010-01-01

    Objective: To determine the frequency of seropositive dengue infection using rapid immuno chromatographic assay in patients with probable dengue infection as per WHO criteria. Method: A cross-sectional observational study was conducted at Abbasi Shaheed Hospital, Karachi from July 2008 to January 2009. Patients presenting with acute febrile illness, rashes, bleeding tendencies, leucopenia and or thrombocytopenia were evaluated according to WHO criteria for probable dengue infection. Acute phase sera were collected after 5 days of the onset of fever as per WHO criteria. Serology was performed using rapid immuno chromatographic (ICT) assay with differential detection of IgM and IgG. A primary dengue infection was defined by a positive IgM band and a negative IgG band whereas secondary infection was defined by a positive IgG band with or without positive IgM band. Result: Among 599 patients who met the WHO criteria for dengue infection, 251(41.9%) were found to be ICT reactive among whom 42 (16.73%) had primary infection. Secondary infection was reported in 209 (83.26%). Acute phase sera of 348 (58.09%) were ICT non reactive. Four patients died because of dengue shock syndrome among which three had secondary infection. Conclusion: Early identification of secondary infection in acute phase sera using rapid ICT is valuable in terms of disease progression and mortality. However in highly suspected cases of dengue infection clinical management should not rely on negative serological results. (author)

  7. Glycosylation of dengue virus glycoproteins and their interactions with carbohydrate receptors: possible targets for antiviral therapy.

    Science.gov (United States)

    Idris, Fakhriedzwan; Muharram, Siti Hanna; Diah, Suwarni

    2016-07-01

    Dengue virus, an RNA virus belonging to the genus Flavivirus, affects 50 million individuals annually, and approximately 500,000-1,000,000 of these infections lead to dengue hemorrhagic fever or dengue shock syndrome. With no licensed vaccine or specific antiviral treatments available to prevent dengue infection, dengue is considered a major public health problem in subtropical and tropical regions. The virus, like other enveloped viruses, uses the host's cellular enzymes to synthesize its structural (C, E, and prM/M) and nonstructural proteins (NS1-5) and, subsequently, to glycosylate these proteins to produce complete and functional glycoproteins. The structural glycoproteins, specifically the E protein, are known to interact with the host's carbohydrate receptors through the viral proteins' N-glycosylation sites and thus mediate the viral invasion of cells. This review focuses on the involvement of dengue glycoproteins in the course of infection and the virus' exploitation of the host's glycans, especially the interactions between host receptors and carbohydrate moieties. We also discuss the recent developments in antiviral therapies that target these processes and interactions, focusing specifically on the use of carbohydrate-binding agents derived from plants, commonly known as lectins, to inhibit the progression of infection.

  8. PEMERIKSAAN VIRUS DENGUE-3 PADA NYAMUK Aedes aegypti YANG DIINFEKSI SECARA INTRATHORAKAL DENGAN TEKNIK IMUNOSITOKIMIA MENGGUNAKAN ANTIBODI DSSE10

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    Dyah Widiastuti

    2013-09-01

    Full Text Available ABSTRACTDengue viruses, globally the most prevalent arboviruses, are transmitted to humans by persistently infectedAedes mosquitoes. The most important vector of Dengue virus is the mosquito Ae.aegypti, which should be the main targetof surveillance and control activities. Virologic surveillance for dengue viruses in its vector has been used as an earlywarning system to predict outbreaks. Detection of Dengue virus antigen in mosquito head squash usingimmunocytochemical streptavidin biotin peroxidase complex (SBPC assay is an alternative method for dengue vectorsurveillance. The study aimed to develope immunocytochemical SBPC assay to detect Dengue virus infection in headsquash of Ae.aegypti. The study design was experimental. Artificially-infected adult Ae. aegypti mosquitoes of DENV 3were used as infectious samples and non-infected adult Ae. aegypti mosquitoes were used as normal ones. Theimmunocytochemical SBPC assay using monoclonal antibody DSSE10 then was applied in mosquito head squash todetect Dengue virus antigen. The results were analyzed by descriptive analysis. The immunocytochemical SBPC assaycan detect Dengue virus antigen in mosquito head squash at day 2 postinfection. There are some false positive resultsfound in immunocytochemical SBPC assay.Key Word: Dengue, immunocytochemistry, DSSE10

  9. Dengue viruses in Brazil, 1986-2006 Virus del dengue en Brasil, 1986-2006

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    Rita Maria Ribeiro Nogueira

    2007-11-01

    Full Text Available A total of 4 243 049 dengue cases have been reported in Brazil between 1981 and 2006, including 5 817 cases of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS and a total of 338 fatal cases. Although all Brazilian regions have been affected, the Northeast and Southeast regions have registered the highest number of notifications. DENV-1 and DENV-4 were isolated for the first time in the Amazon region of Brazil in 1981 and 1982. The disease became a nationwide public health problem following outbreaks of DENV-1 and DENV-2 in the state of Rio de Janeiro in 1986 and 1990, respectively. The introduction of DENV-3 in 2000, also in the state of Rio de Janeiro, led to a severe epidemic with 288 245 reported dengue cases, including 91 deaths. Virus strains that were typed during the 2002 epidemic show that DENV-3 has displaced other dengue virus serotypes and entered new areas, a finding that warrants closer evaluation. Unusual clinical symptoms, including central nervous system involvement, have been observed in dengue patients in at least three regions of the country.En Brasil se han notificado 4 243 049 casos de dengue entre 1981 y 2006, de ellos 5 817 casos de dengue hemorrágico/síndrome de choque por dengue (DH/SCD y un total de 338 casos mortales. A pesar de que la enfermedad ha afectado a todas las regiones brasileñas, el mayor número de casos se ha notificado en las regiones nororiental y suroriental. Los virus del dengue (DENV 1 y 4 se aislaron por primera vez en la región amazónica de Brasil en 1981 y 1982. La enfermedad se convirtió en un problema nacional de salud pública después de los brotes de DENV-1 y DENV-2 en el Estado de Río de Janeiro en 1986 y 1990, respectivamente. La introducción del DENV-3 en 2000, también en el Estado de Río de Janeiro, llevó a una grave epidemia con 288 245 casos notificados de dengue y 91 muertes. Las cepas del virus identificadas durante la epidemia de 2002 demostraron que el DENV-3 ha

  10. Chloroquine Inhibits Dengue Virus Type 2 Replication in Vero Cells but Not in C6/36 Cells

    OpenAIRE

    Farias, Kleber Juvenal Silva; Machado, Paula Renata Lima; da Fonseca, Benedito Antônio Lopes

    2013-01-01

    Dengue viruses are the most important arthropod-borne viruses in terms of morbidity and mortality in the world. Since there is no dengue vaccine available for human use, we have set out to investigate the use of chloroquine as an antiviral drug against dengue. Chloroquine, an amine acidotropic drug known to affect intracellular exocytic pathways by increasing endosomal pH, was used in the in vitro treatment of Vero and C6/36 cells infected with dengue virus type 2 (DENV-2). Real-time RT-PCR a...

  11. Unusual dengue virus 3 epidemic in Nicaragua, 2009.

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    Gamaliel Gutierrez

    2011-11-01

    Full Text Available The four dengue virus serotypes (DENV1-4 cause the most prevalent mosquito-borne viral disease affecting humans worldwide. In 2009, Nicaragua experienced the largest dengue epidemic in over a decade, marked by unusual clinical presentation, as observed in two prospective studies of pediatric dengue in Managua. From August 2009-January 2010, 212 dengue cases were confirmed among 396 study participants at the National Pediatric Reference Hospital. In our parallel community-based cohort study, 170 dengue cases were recorded in 2009-10, compared to 13-65 cases in 2004-9. In both studies, significantly more patients experienced "compensated shock" (poor capillary refill plus cold extremities, tachycardia, tachypnea, and/or weak pulse in 2009-10 than in previous years (42.5% [90/212] vs. 24.7% [82/332] in the hospital study (p<0.001 and 17% [29/170] vs. 2.2% [4/181] in the cohort study (p<0.001. Signs of poor peripheral perfusion presented significantly earlier (1-2 days in 2009-10 than in previous years according to Kaplan-Meier survival analysis. In the hospital study, 19.8% of subjects were transferred to intensive care, compared to 7.1% in previous years - similar to the cohort study. DENV-3 predominated in 2008-9, 2009-10, and 2010-11, and full-length sequencing revealed no major genetic changes from 2008-9 to 2010-11. In 2008-9 and 2010-11, typical dengue was observed; only in 2009-10 was unusual presentation noted. Multivariate analysis revealed only "2009-10" as a significant risk factor for Dengue Fever with Compensated Shock. Interestingly, circulation of pandemic influenza A-H1N1 2009 in Managua was shifted such that it overlapped with the dengue epidemic. We hypothesize that prior influenza A H1N1 2009 infection may have modulated subsequent DENV infection, and initial results of an ongoing study suggest increased risk of shock among children with anti-H1N1-2009 antibodies. This study demonstrates that parameters other than serotype, viral

  12. Zika, dengue, and chikungunya co-infection in a pregnant woman from Colombia

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    Wilmer E. Villamil-Gómez

    2016-10-01

    Full Text Available The clinical findings of a pregnant woman from Colombia with a triple co-infection caused by dengue, chikungunya, and Zika viruses are described. Weekly obstetric ultrasounds from 14.6 to 29 weeks of gestation were normal. She remains under follow-up and management according to the standard guidelines for the management of Zika virus-infected pregnant women.

  13. Dengue encephalitis–A rare manifestation of dengue fever

    OpenAIRE

    Madi, Deepak; Achappa, Basavaprabhu; Ramapuram, John T; Chowta, Nityananda; Laxman, Mridula; Mahalingam, Soundarya

    2014-01-01

    The clinical spectrum of dengue fever ranges from asymptomatic infection to dengue shock syndrome. Dengue is classically considered a non-neurotropic virus. Neurological complications are not commonly seen in dengue. The neurological manifestations seen in dengue are encephalitis, meningitis, encephalopathy, stroke and Guillain-Barré syndrome. Dengue encephalitis is a rare disease. We report an interesting case of dengue encephalitis from Southern India. A 49-year-old gentleman presented with...

  14. Dengue and Severe Dengue

    Science.gov (United States)

    ... all regions of WHO in recent years. Dengue virus is transmitted by female mosquitoes mainly of the species Aedes aegypti and, to a lesser extent, Ae. albopictus . This mosquito also transmits chikungunya, yellow fever and Zika infection. Dengue is widespread throughout the tropics, with ...

  15. Two complex, adenovirus-based vaccines that together induce immune responses to all four dengue virus serotypes.

    Science.gov (United States)

    Holman, David H; Wang, Danher; Raviprakash, Kanakatte; Raja, Nicholas U; Luo, Min; Zhang, Jianghui; Porter, Kevin R; Dong, John Y

    2007-02-01

    Dengue virus infections can cause hemorrhagic fever, shock, encephalitis, and even death. Worldwide, approximately 2.5 billion people live in dengue-infested regions with about 100 million new cases each year, although many of these infections are believed to be silent. There are four antigenically distinct serotypes of dengue virus; thus, immunity from one serotype will not cross-protect from infection with the other three. The difficulties that hamper vaccine development include requirements of the natural conformation of the envelope glycoprotein to induce neutralizing immune responses and the necessity of presenting antigens of all four serotypes. Currently, the only way to meet these requirements is to use a mixture of four serotypes of live attenuated dengue viruses, but safety remains a major problem. In this study, we have developed the basis for a tetravalent dengue vaccine using a novel complex adenovirus platform that is capable of expressing multiple antigens de novo. This dengue vaccine is constructed as a pair of vectors that each expresses the premembrane and envelope genes of two different dengue virus serotypes. Upon vaccination, the vaccine expressed high levels of the dengue virus antigens in cells to mimic a natural infection and induced both humoral and cellular immune responses against multiple serotypes of dengue virus in an animal model. Further analyses show the humoral responses were indeed neutralizing against all four serotypes. Our studies demonstrate the concept of mimicking infections to induce immune responses by synthesizing dengue virus membrane antigens de novo and the feasibility of developing an effective tetravalent dengue vaccine by vector-mediated expression of glycoproteins of the four serotypes.

  16. Characterization of Dengue Virus Resistance to Brequinar in Cell Culture▿

    Science.gov (United States)

    Qing, Min; Zou, Gang; Wang, Qing-Yin; Xu, Hao Ying; Dong, Hongping; Yuan, Zhiming; Shi, Pei-Yong

    2010-01-01

    Brequinar is an inhibitor of dihydroorotate dehydrogenase, an enzyme that is required for de novo pyrimidine biosynthesis. Here we report that brequinar has activity against a broad spectrum of viruses. The compound not only inhibits flaviviruses (dengue virus, West Nile virus, yellow fever virus, and Powassan virus) but also suppresses a plus-strand RNA alphavirus (Western equine encephalitis virus) and a negative-strand RNA rhabdovirus (vesicular stomatitis virus). Using dengue virus serotype 2 (DENV-2) as a model, we found that brequinar suppressed the viral infection cycle mainly at the step of RNA synthesis. Supplementing the culture medium with pyrimidines (cytidine or uridine) but not purines (adenine or guanine) could be used to reverse the inhibitory effect of the compound. Continuous culturing of DENV-2 in the presence of brequinar generated viruses that were partially resistant to the inhibitor. Sequencing of the resistant viruses revealed two amino acid mutations: one mutation (M260V) located at a helix in the domain II of the viral envelope protein and another mutation (E802Q) located at the priming loop of the nonstructural protein 5 (NS5) polymerase domain. Functional analysis of the mutations suggests that the NS5 mutation exerts resistance through enhancement of polymerase activity. The envelope protein mutation reduced the efficiency of virion assembly/release; however, the mutant virus became less sensitive to brequinar inhibition at the step of virion assembly/release. Taken together, the results indicate that (i) brequinar blocks DENV RNA synthesis through depletion of intracellular pyrimidine pools and (ii) the compound may also exert its antiviral activity through inhibition of virion assembly/release. PMID:20606073

  17. Is clinical outcome of dengue-virus infections influenced by coagulation and fibrinolysis? A critical review of the evidence.

    NARCIS (Netherlands)

    Mairuhu, A.T.; MacGillavry, M.R.; Setiati, T.E.; Soemantri, A.; Cate, H. ten; Brandjes, D.P.; Gorp, E. van

    2003-01-01

    Despite efforts to elucidate the pathogenesis of dengue fever, the progression into severe disease remains poorly understood. In-vitro findings suggest that coagulopathy and disturbances in fibrinolysis have a pivotal role in the pathophysiology. If disturbances in these processes are predictive of

  18. Coinfection with influenza A(H1N1)pdm09 and dengue virus in fatal cases.

    Science.gov (United States)

    Perdigão, Anne Carolinne Bezerra; Ramalho, Izabel Letícia Cavalcante; Guedes, Maria Izabel Florindo; Braga, Deborah Nunes Melo; Cavalcanti, Luciano Pamplona Góes; Melo, Maria Elisabeth Lisboa de; Araújo, Rafael Montenegro de Carvalho; Lima, Elza Gadelha; Silva, Luciene Alexandre Bié da; Araújo, Lia de Carvalho; Araújo, Fernanda Montenegro de Carvalho

    2016-09-01

    We report on four patients with fatal influenza A(H1N1)pdm09 and dengue virus coinfections. Clinical, necropsy and histopathologic findings presented in all cases were characteristic of influenza-dengue coinfections, and all were laboratory-confirmed for both infections. The possibility of influenza and dengue coinfection should be considered in locations where these two viruses' epidemic periods coincide to avoid fatal outcomes. Dengue is a mosquito-borne viral infection caused by one of the four dengue viruses (DENV-1 to 4). Each of these viruses is capable of causing nonspecific febrile illnesses, classic dengue fever and dengue haemorrhagic fever (Gubler 1998). As a result, dengue is often difficult to diagnose clinically, especially because peak dengue season often coincides with that of other common febrile illnesses in tropical regions (Chacon et al. 2015). In April 2009, a new virus, influenza A/H1N1/pandemic (FluA/H1N1/09pdm), caused a severe outbreak in Mexico. The virus quickly spread throughout the world, and in June 2009, the World Health Organization declared a pandemic (WHO 2010). In Brazil, the first laboratory confirmed case of FluA/H1N1/09pdm was in July 2009 (Pires Neto et al. 2013). The state of Ceará, in Northeast Brazil, is a dengue endemic area. In this state, the virus influenza A(H1N1)pdm09 has circulated since 2009, and through the first half of 2012, 11 deaths caused by the virus were confirmed (Pires Neto et al. 2013). The influenza and dengue seasons in Ceará overlap, which led to diagnostic difficulties. We report four cases of laboratory-confirmed coinfection of deadly influenza A(H1N1)pdm09 with DENV, which occurred during the dengue and influenza season in 2012 and 2013 in Ceará.

  19. Detection of dengue group viruses by fluorescence in situ hybridization

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    Raquin Vincent

    2012-10-01

    Full Text Available Abstract Background Dengue fever (DF and dengue hemorrhagic fever (DHF represent a global challenge in public health. It is estimated that 50 to 100 million infections occur each year causing approximately 20,000 deaths that are usually linked to severe cases like DHF and dengue shock syndrome. The causative agent of DF is dengue virus (genus Flavivirus that comprises four distinct serotypes (DENV-1 to DENV-4. Fluorescence in situ hybridization (FISH has been used successfully to detect pathogenic agents, but has not been implemented in detecting DENV. To improve our understanding of DENV infection and dissemination in host tissues, we designed specific probes to detect DENV in FISH assays. Methods Oligonucleotide probes were designed to hybridize with RNA from the broadest range of DENV isolates belonging to the four serotypes, but not to the closest Flavivirus genomes. Three probes that fit the criteria defined for FISH experiments were selected, targeting both coding and non-coding regions of the DENV genome. These probes were tested in FISH assays against the dengue vector Aedes albopictus (Diptera: Culicidae. The FISH experiments were led in vitro using the C6/36 cell line, and in vivo against dissected salivary glands, with epifluorescence and confocal microscopy. Results The three 60-nt oligonucleotides probes DENV-Probe A, B and C cover a broad range of DENV isolates from the four serotypes. When the three probes were used together, specific fluorescent signals were observed in C6/36 infected with each DENV serotypes. No signal was detected in either cells infected with close Flavivirus members West Nile virus or yellow fever virus. The same protocol was used on salivary glands of Ae. albopictus fed with a DENV-2 infectious blood-meal which showed positive signals in the lateral lobes of infected samples, with no significant signal in uninfected mosquitoes. Conclusion Based on the FISH technique, we propose a way to design and use

  20. Differential oxidative stress induced by dengue virus in monocytes from human neonates, adult and elderly individuals.

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    Nereida Valero

    Full Text Available Changes in immune response during lifespan of man are well known. These changes involve decreased neonatal and elderly immune response. In addition, it has been shown a relationship between immune and oxidative mechanisms, suggesting that altered immune response could be associated to altered oxidative response. Increased expression of nitric oxide (NO has been documented in dengue and in monocyte cultures infected with different types of dengue virus. However, there is no information about the age-dependent NO oxidative response in humans infected by dengue virus. In this study, monocyte cultures from neonatal, elderly and adult individuals (n = 10 each group were infected with different dengue virus types (DENV- 1 to 4 and oxidative/antioxidative responses and apoptosis were measured at days 1 and 3 of culture. Increased production of NO, lipid peroxidation and enzymatic and nonenzymatic anti-oxidative responses in dengue infected monocyte cultures were observed. However, neonatal and elderly monocytes had lower values of studied parameters when compared to those in adult-derived cultures. Apoptosis was present in infected monocytes with higher values at day 3 of culture. This reduced oxidant/antioxidant response of neonatal and elderly monocytes could be relevant in the pathogenesis of dengue disease.

  1. Predictive diagnostic value of the tourniquet test for the diagnosis of dengue infection in adults

    Science.gov (United States)

    Mayxay, Mayfong; Phetsouvanh, Rattanaphone; Moore, Catrin E; Chansamouth, Vilada; Vongsouvath, Manivanh; Sisouphone, Syho; Vongphachanh, Pankham; Thaojaikong, Thaksinaporn; Thongpaseuth, Soulignasack; Phongmany, Simmaly; Keolouangkhot, Valy; Strobel, Michel; Newton, Paul N

    2011-01-01

    Objective To examine the accuracy of the admission tourniquet test in the diagnosis of dengue infection among Lao adults. Methods Prospective assessment of the predictive diagnostic value of the tourniquet test for the diagnosis of dengue infection, as defined by IgM, IgG and NS1 ELISAs (Panbio Ltd, Australia), among Lao adult inpatients with clinically suspected dengue infection. Results Of 234 patients with clinically suspected dengue infection on admission, 73% were serologically confirmed to have dengue, while 64 patients with negative dengue serology were diagnosed as having scrub typhus (39%), murine typhus (11%), undetermined typhus (12%), Japanese encephalitis virus (5%), undetermined flavivirus (5%) and typhoid fever (3%); 25% had no identifiable aetiology. The tourniquet test was positive in 29.1% (95% CI = 23.2–34.9%) of all patients and in 34.1% (95% CI = 27.0–41.2%) of dengue-seropositive patients, in 32.7% (95% CI = 23.5–41.8) of those with dengue fever and in 36.4% (95% CI = 24.7–48.0) of those with dengue haemorrhagic fever. Interobserver agreement for the tourniquet test was 90.2% (95% CI = 86.4–94.0) (Kappa = 0.76). Using ELISAs as the diagnostic gold standard, the sensitivity of the tourniquet test was 33.5–34%; its specificity was 84–91%. The positive and negative predictive values were 85–90% and 32.5–34%, respectively. Conclusions The admission tourniquet test has low sensitivity and adds relatively little value to the diagnosis of dengue among Lao adult inpatients with suspected dengue. Although a positive tourniquet test suggests dengue and that treatment of alternative diagnoses may not be needed, a negative test result does not exclude dengue. PMID:20958892

  2. A brief review on dengue molecular virology, diagnosis, treatment and prevalence in Pakistan

    OpenAIRE

    Idrees, Sobia; Ashfaq, Usman A

    2012-01-01

    Dengue virus infection is a serious health problem infecting 2.5 billion people worldwide. Dengue is now endemic in more than 100 countries, including Pakistan. Each year hundreds of people get infected with dengue in Pakistan. Currently, there is no vaccine available for the prevention of Dengue virus infection due to four viral serotypes. Dengue infection can cause death of patients in its most severity, meanwhile many antiviral compounds are being tested against dengue virus infection to e...

  3. Dengue Epidemiology

    Science.gov (United States)

    ... and dengue shock syndrome (DSS). Transmission of the Dengue Virus Dengue is transmitted between people by the ... the vectors is too infrequent to sustain transmission. Dengue is an Emerging Disease The four dengue viruses ...

  4. Aedes albopictus (Skuse, 1894 infected with the American-Asian genotype of dengue type 2 virus in Medellín suggests its possible role as vector of dengue fever in Colombia

    Directory of Open Access Journals (Sweden)

    Andrés Gómez-Palacio

    2017-03-01

    Conclusion: We report the presence Ae. albopictus naturally infected with the Asian-American genotype of DENV-2 in Colombia. The presence of Ae. albopictus specimens carrying the most common genotype infecting humans in a highly populated city such as Medellín indicates its potential role as dengue vector in Colombia and highlights the relevance of including it in current vector surveillance strategies.

  5. Human T Lymphocytes Are Permissive for Dengue Virus Replication.

    Science.gov (United States)

    Silveira, Guilherme F; Wowk, Pryscilla F; Cataneo, Allan H D; Dos Santos, Paula F; Delgobo, Murilo; Stimamiglio, Marco A; Lo Sarzi, Maria; Thomazelli, Ana Paula F S; Conchon-Costa, Ivete; Pavanelli, Wander R; Antonelli, Lis R V; Báfica, André; Mansur, Daniel S; Dos Santos, Claudia N Duarte; Bordignon, Juliano

    2018-05-15

    Dengue virus (DV) infection can cause either a self-limiting flu-like disease or a threatening hemorrhage that may evolve to shock and death. A variety of cell types, such as dendritic cells, monocytes, and B cells, can be infected by DV. However, despite the role of T lymphocytes in the control of DV replication, there remains a paucity of information on possible DV-T cell interactions during the disease course. In the present study, we have demonstrated that primary human naive CD4 + and CD8 + T cells are permissive for DV infection. Importantly, both T cell subtypes support viral replication and secrete viable virus particles. DV infection triggers the activation of both CD4 + and CD8 + T lymphocytes, but preactivation of T cells reduces the susceptibility of T cells to DV infection. Interestingly, the cytotoxicity-inducing protein granzyme A is highly secreted by human CD4 + but not CD8 + T cells after exposure to DV in vitro Additionally, using annexin V and polycaspase assays, we have demonstrated that T lymphocytes, in contrast to monocytes, are resistant to DV-induced apoptosis. Strikingly, both CD4 + and CD8 + T cells were found to be infected with DV in acutely infected dengue patients. Together, these results show that T cells are permissive for DV infection in vitro and in vivo , suggesting that this cell population may be a viral reservoir during the acute phase of the disease. IMPORTANCE Infection by dengue virus (DV) causes a flu-like disease that can evolve to severe hemorrhaging and death. T lymphocytes are important cells that regulate antibody secretion by B cells and trigger the death of infected cells. However, little is known about the direct interaction between DV and T lymphocytes. Here, we show that T lymphocytes from healthy donors are susceptible to infection by DV, leading to cell activation. Additionally, T cells seem to be resistant to DV-induced apoptosis, suggesting a potential role as a viral reservoir in humans. Finally, we show

  6. Coinfection with influenza A(H1N1pdm09 and dengue virus in fatal cases

    Directory of Open Access Journals (Sweden)

    Anne Carolinne Bezerra Perdigão

    2016-01-01

    Full Text Available Abstract We report on four patients with fatal influenza A(H1N1pdm09 and dengue virus coinfections. Clinical, necropsy and histopathologic findings presented in all cases were characteristic of influenza-dengue coinfections, and all were laboratory-confirmed for both infections. The possibility of influenza and dengue coinfection should be considered in locations where these two viruses’ epidemic periods coincide to avoid fatal outcomes. Dengue is a mosquito-borne viral infection caused by one of the four dengue viruses (DENV-1 to 4. Each of these viruses is capable of causing nonspecific febrile illnesses, classic dengue fever and dengue haemorrhagic fever (Gubler 1998. As a result, dengue is often difficult to diagnose clinically, especially because peak dengue season often coincides with that of other common febrile illnesses in tropical regions (Chacon et al. 2015. In April 2009, a new virus, influenza A/H1N1/pandemic (FluA/H1N1/09pdm, caused a severe outbreak in Mexico. The virus quickly spread throughout the world, and in June 2009, the World Health Organization declared a pandemic (WHO 2010. In Brazil, the first laboratory confirmed case of FluA/H1N1/09pdm was in July 2009 (Pires Neto et al. 2013. The state of Ceará, in Northeast Brazil, is a dengue endemic area. In this state, the virus influenza A(H1N1pdm09 has circulated since 2009, and through the first half of 2012, 11 deaths caused by the virus were confirmed (Pires Neto et al. 2013. The influenza and dengue seasons in Ceará overlap, which led to diagnostic difficulties. We report four cases of laboratory-confirmed coinfection of deadly influenza A(H1N1pdm09 with DENV, which occurred during the dengue and influenza season in 2012 and 2013 in Ceará.

  7. Identification of bioflavonoid as fusion inhibitor of dengue virus using molecular docking approach

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    Asif Mir

    Full Text Available Dengue virus with four distinct serotypes belongs to Flavivirus, poses a significant threat to human health and becomes an emerging global problem. Membrane fusion is a central molecular event during viral entry into host cell. To prevent viral infection it is necessary to interrupt the virus replication at an early stage of attachment. Dengue Virus (DENV envelope protein experiences conformational changes and it causes the virus to fuse with host cell. Hinge region movement of domain I and II in envelope protein facilitates the fusion process. Small molecules that bind in this pocket may have the ability to interrupt the conformational changes that trigger fusion process. We chose different flavonoids (baicalein, fisetin, hesperetin, naringenin/ naringin, quercetin and rutin that possess anti dengue activity. Molecular docking analysis was done to examine the inhibitory effect of flavonoids against envelope protein of DENV-2. Results manifest quercetin (flavonoid found in Carica papaya, apple and even in lemon as the only flavone that can interrupt the fusion process of virus by inhibiting the hinge region movement and by blocking the conformational rearrangement in envelope protein. These novel findings using computational approach are worthwhile and will be a bridge to check the efficacy of compounds using appropriate animal model under In vivo studies. This information can be used by new techniques and provides a way to control dengue virus infection. Keywords: Dengue virus, Inhibitor identification, Molecular docking, Interaction analysis

  8. Genetic analysis of imported dengue virus strains by Iranian travelers

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    Nariman Shahhosseini

    2016-11-01

    Full Text Available Dengue virus sequences used in this study were obtained from two Iranian patients who were both with a history of traveling to Malaysia. The maximum likelihood phylogenetic tree demonstrated that two sequences were grouped into dengue virus 1. Specifically, strains IranDF1 and Iran-DF2 clustered in genotype I and III, respectively.

  9. Antiviral Activity of Novel Quinoline Derivatives against Dengue Virus Serotype 2

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    Carolina de la Guardia

    2018-03-01

    Full Text Available Dengue virus causes dengue fever, a debilitating disease with an increasing incidence in many tropical and subtropical territories. So far, there are no effective antivirals licensed to treat this virus. Here we describe the synthesis and antiviral activity evaluation of two compounds based on the quinoline scaffold, which has shown potential for the development of molecules with various biological activities. Two of the tested compounds showed dose-dependent inhibition of dengue virus serotype 2 in the low and sub micromolar range. The compounds 1 and 2 were also able to impair the accumulation of the viral envelope glycoprotein in infected cells, while showing no sign of direct virucidal activity and acting possibly through a mechanism involving the early stages of the infection. The results are congruent with previously reported data showing the potential of quinoline derivatives as a promising scaffold for the development of new antivirals against this important virus.

  10. Vaccination with dengue virus-like particles induces humoral and cellular immune responses in mice

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    Zhang Quanfu

    2011-06-01

    Full Text Available Abstract Background The incidence of dengue, an infectious disease caused by dengue virus (DENV, has dramatically increased around the world in recent decades and is becoming a severe public health threat. However, there is currently no specific treatment for dengue fever, and licensed vaccine against dengue is not available. Vaccination with virus-like particles (VLPs has shown considerable promise for many viral diseases, but the effect of DENV VLPs to induce specific immune responses has not been adequately investigated. Results By optimizing the expression plasmids, recombinant VLPs of four antigenically different DENV serotypes DENV1-4 were successfully produced in 293T cells. The vaccination effect of dengue VLPs in mice showed that monovalent VLPs of each serotype stimulated specific IgG responses and potent neutralizing antibodies against homotypic virus. Tetravalent VLPs efficiently enhanced specific IgG and neutralizing antibodies against all four serotypes of DENV. Moreover, vaccination with monovalent or tetravalent VLPs resulted in the induction of specific cytotoxic T cell responses. Conclusions Mammalian cell expressed dengue VLPs are capable to induce VLP-specific humoral and cellular immune responses in mice, and being a promising subunit vaccine candidate for prevention of dengue virus infection.

  11. Phylogenetic analysis of Dengue virus 1 isolated from South Minas Gerais, Brazil.

    Science.gov (United States)

    Drumond, Betania Paiva; Fagundes, Luiz Gustavo da Silva; Rocha, Raissa Prado; Fumagalli, Marcilio Jorge; Araki, Carlos Shigueru; Colombo, Tatiana Elisa; Nogueira, Mauricio Lacerda; Castilho, Thiago Elias; da Silveira, Nelson José Freitas; Malaquias, Luiz Cosme Cotta; Coelho, Luiz Felipe Leomil

    2016-01-01

    Dengue is a major worldwide public health problem, especially in the tropical and subtropical regions of the world. Primary infection with a single Dengue virus serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients who experience secondary infection with a different serotype can progress to a more severe form of the disease, called dengue hemorrhagic fever. The four Dengue virus serotypes (1-4) are antigenically and genetically distinct and each serotype is composed of multiple genotypes. In this study we isolated one Dengue virus 1 serotype, named BR/Alfenas/2012, from a patient with dengue hemorrhagic fever in Alfenas, South Minas Gerais, Brazil and molecular identification was performed based on the analysis of NS5 gene. Swiss mice were infected with this isolate to verify its potential to induce histopathological alterations characteristic of dengue. Liver histopathological analysis of infected animals showed the presence of inflammatory infiltrates, hepatic steatosis, as well as edema, hemorrhage and necrosis focal points. Phylogenetic and evolutionary analyses based on the envelope gene provided evidence that the isolate BR/Alfenas/2012 belongs to genotype V, lineage I and it is probably derived from isolates of Rio de Janeiro, Brazil. The isolate BR/Alfenas/2012 showed two unique amino acids substitutions (SER222THRE and PHE306SER) when compared to other Brazilian isolates from the same genotype/lineage. Molecular models were generated for the envelope protein indicating that the amino acid alteration PHE 306 SER could contribute to a different folding in this region located within the domain III. Further genetic and animal model studies using BR/Alfenas/2012 and other isolates belonging to the same lineage/genotype could help determine the relation of these genetic alterations and dengue hemorrhagic fever in a susceptible population. Copyright © 2015 Sociedade Brasileira de Microbiologia. Published by

  12. Phylogenetic analysis of Dengue virus 1 isolated from South Minas Gerais, Brazil

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    Betania Paiva Drumond

    2016-03-01

    Full Text Available Abstract Dengue is a major worldwide public health problem, especially in the tropical and subtropical regions of the world. Primary infection with a single Dengue virus serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients who experience secondary infection with a different serotype can progress to a more severe form of the disease, called dengue hemorrhagic fever. The four Dengue virus serotypes (1–4 are antigenically and genetically distinct and each serotype is composed of multiple genotypes. In this study we isolated one Dengue virus 1 serotype, named BR/Alfenas/2012, from a patient with dengue hemorrhagic fever in Alfenas, South Minas Gerais, Brazil and molecular identification was performed based on the analysis of NS5 gene. Swiss mice were infected with this isolate to verify its potential to induce histopathological alterations characteristic of dengue. Liver histopathological analysis of infected animals showed the presence of inflammatory infiltrates, hepatic steatosis, as well as edema, hemorrhage and necrosis focal points. Phylogenetic and evolutionary analyses based on the envelope gene provided evidence that the isolate BR/Alfenas/2012 belongs to genotype V, lineage I and it is probably derived from isolates of Rio de Janeiro, Brazil. The isolate BR/Alfenas/2012 showed two unique amino acids substitutions (SER222THRE and PHE306SER when compared to other Brazilian isolates from the same genotype/lineage. Molecular models were generated for the envelope protein indicating that the amino acid alteration PHE 306 SER could contribute to a different folding in this region located within the domain III. Further genetic and animal model studies using BR/Alfenas/2012 and other isolates belonging to the same lineage/genotype could help determine the relation of these genetic alterations and dengue hemorrhagic fever in a susceptible population.

  13. Evidence of dengue virus transmission and factors associated with the presence of anti-dengue virus antibodies in humans in three major towns in Cameroon.

    Science.gov (United States)

    Demanou, Maurice; Pouillot, Régis; Grandadam, Marc; Boisier, Pascal; Kamgang, Basile; Hervé, Jean Pierre; Rogier, Christophe; Rousset, Dominique; Paupy, Christophe

    2014-07-01

    Dengue is not well documented in Africa. In Cameroon, data are scarce, but dengue infection has been confirmed in humans. We conducted a study to document risk factors associated with anti-dengue virus Immunoglobulin G seropositivity in humans in three major towns in Cameroon. A cross sectional survey was conducted in Douala, Garoua and Yaounde, using a random cluster sampling design. Participants underwent a standardized interview and were blood sampled. Environmental and housing characteristics were recorded. Randomized houses were prospected to record all water containers, and immature stages of Aedes mosquitoes were collected. Sera were screened for anti-dengue virus IgG and IgM antibodies. Risk factors of seropositivity were tested using logistic regression methods with random effects. Anti-dengue IgG were found from 61.4% of sera in Douala (n = 699), 24.2% in Garoua (n = 728) and 9.8% in Yaounde (n = 603). IgM were found from 0.3% of Douala samples, 0.1% of Garoua samples and 0.0% of Yaounde samples. Seroneutralization on randomly selected IgG positive sera showed that 72% (n = 100) in Douala, 80% (n = 94) in Garoua and 77% (n = 66) in Yaounde had antibodies specific for dengue virus serotype 2 (DENV-2). Age, temporary house walls materials, having water-storage containers, old tires or toilets in the yard, having no TV, having no air conditioning and having travelled at least once outside the city were independently associated with anti-dengue IgG positivity in Douala. Age, having uncovered water containers, having no TV, not being born in Garoua and not breeding pigs were significant risk factors in Garoua. Recent history of malaria, having banana trees and stagnant water in the yard were independent risk factors in Yaounde. In this survey, most identified risk factors of dengue were related to housing conditions. Poverty and underdevelopment are central to the dengue epidemiology in Cameroon.

  14. Validation of dengue infection severity score

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    Pongpan S

    2014-03-01

    Full Text Available Surangrat Pongpan,1,2 Jayanton Patumanond,3 Apichart Wisitwong,4 Chamaiporn Tawichasri,5 Sirianong Namwongprom1,6 1Clinical Epidemiology Program, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 2Department of Occupational Medicine, Phrae Hospital, Phrae, Thailand; 3Clinical Epidemiology Program, Faculty of Medicine, Thammasat University, Bangkok, Thailand; 4Department of Social Medicine, Sawanpracharak Hospital, Nakorn Sawan, Thailand; 5Clinical Epidemiology Society at Chiang Mai, Chiang Mai, Thailand; 6Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Objective: To validate a simple scoring system to classify dengue viral infection severity to patients in different settings. Methods: The developed scoring system derived from 777 patients from three tertiary-care hospitals was applied to 400 patients in the validation data obtained from another three tertiary-care hospitals. Percentage of correct classification, underestimation, and overestimation was compared. The score discriminative performance in the two datasets was compared by analysis of areas under the receiver operating characteristic curves. Results: Patients in the validation data were different from those in the development data in some aspects. In the validation data, classifying patients into three severity levels (dengue fever, dengue hemorrhagic fever, and dengue shock syndrome yielded 50.8% correct prediction (versus 60.7% in the development data, with clinically acceptable underestimation (18.6% versus 25.7% and overestimation (30.8% versus 13.5%. Despite the difference in predictive performances between the validation and the development data, the overall prediction of the scoring system is considered high. Conclusion: The developed severity score may be applied to classify patients with dengue viral infection into three severity levels with clinically acceptable under- or overestimation. Its impact when used in routine

  15. Vectors expressing chimeric Japanese encephalitis dengue 2 viruses.

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    Wei, Y; Wang, S; Wang, X

    2014-01-01

    Vectors based on self-replicating RNAs (replicons) of flaviviruses are becoming powerful tool for expression of heterologous genes in mammalian cells and development of novel antiviral and anticancer vaccines. We constructed two vectors expressing chimeric viruses consisting of attenuated SA14-14-2 strain of Japanese encephalitis virus (JEV) in which the PrM/M-E genes were replaced fully or partially with those of dengue 2 virus (DENV-2). These vectors, named pJED2 and pJED2-1770 were transfected to BHK-21 cells and produced chimeric viruses JED2V and JED2-1770V, respectively. The chimeric viruses could be passaged in C6/36 but not BHK-21 cells. The chimeric viruses produced in C6/36 cells CPE 4-5 days after infection and RT-PCR, sequencing, immunofluorescence assay (IFA) and Western blot analysis confirmed the chimeric nature of produced viruses. The immunogenicity of chimeric viruses in mice was proved by detecting DENV-2 E protein-specific serum IgG antibodies with neutralization titer of 10. Successful preparation of infectious clones of chimeric JEV-DENV-2 viruses showed that JEV-based expression vectors are fully functional.

  16. Fulminant hepatic failure in an infant with severe dengue infection.

    Science.gov (United States)

    Soundravally, R; Narayanan, P; Bhat, B Vishnu; Soundraragavan, Jayanthi; Setia, Sajita

    2010-04-01

    Fulminant hepatic failure due to dengue infection is rare, although mild liver dysfunction is common. Here we report a fatal case of fulminant hepatitis in an infant infected with dengue 3 serotype. Attention must be given to the use of hepatotoxic drugs in some cases of dengue especially in infants.

  17. Efektivitas Pentagamavunon-0 (PGV-0 pada fase awal infeksi virus Dengue-2

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    Dewi Marbawati

    2015-01-01

    Full Text Available Abstract. Dengue virus infects 50 to 100 million people every year, however, specific treatment or effective antiviral drugs to treat viral infections has not been found yet. Curcumin known has  perform the inhibition of ubiquitin-proteasome system that causes a decrease of Japanese encephalitis, one kind of flavivirus. Structural modifications was known to increase the biological activity of curcumin. Pentagamavunon-0 (PGV-0 is known have activity similar to or even better than curcumin. This study aims to determine the effect of PGV-0 in the early phase of infection of dengue- virus 2 (one day of infection. This study includes quasi-experimental study. The method used for the detection of Dengue-2 viruswas immunocytochemistry, whichpreviously tested by PGV-0 cytotoxic test against vero cells. Cytotoxic test results indicate safe concentrations (no toxic effects of PGV-0 against vero cells is 4.44 µM. Calculation of positive rate compared with the positive control(14.55 ± 7.25 showed that the value of positive rate due to one-day Dengue virus-2 infection with PGV-0 treatment was smaller(3.8 ± 3.89. It was concluded that the PGV-0 is able to decrease the positive rate due to Den-2 infection in the initial period of infection. Keywords: dengue, Pentagamavunon-0 (PGV-0,immunocytochemistry, vero cells Abstrak.Virus Dengue menginfeksi 50 sampai 100 juta orangper tahun, namun terapi yang spesifik atau obat antivirus yang efektif belum ditemukan. Kurkumin diketahui mampu melakukan penghambatan system ubiquitin-proteasome yang menyebabkan penurunan produksi salah satu jenis Flavivirus yaitu Japanese encephaitis. Modifikasi struktur kurkumin terbukti meningkatkan aktivitas biologisnya.  Pentagamavunon-0 (PGV-0 diketahui memiliki aktifitas mirip atau bahkan  lebih baik dari kurkumin. Tujuan dari penelitian ini adalah mengetahui pengaruh pemberian PGV-0 pada fase awal infeksi virus Dengue-2 (satu hari infeksi. Penelitian ini termasuk penelitian

  18. Complexity of Human Antibody Response to Dengue Virus: Implication for Vaccine Development.

    Science.gov (United States)

    Tsai, Wen-Yang; Lin, Hong-En; Wang, Wei-Kung

    2017-01-01

    The four serotypes of dengue virus (DENV) are the leading cause of arboviral diseases in humans. Decades of efforts have made remarkable progress in dengue vaccine development. Despite the first dengue vaccine (dengvaxia from Sanofi Pasteur), a live-attenuated tetravalent chimeric yellow fever-dengue vaccine, has been licensed by several countries since 2016, its overall moderate efficacy (56.5-60.8%) in the presence of neutralizing antibodies during the Phase 2b and 3 trials, lower efficacy among dengue naïve compared with dengue experienced individuals, and increased risk of hospitalization among young children during the follow-up highlight the need for a better understanding of humoral responses after natural DENV infection. Recent studies of more than 300 human monoclonal antibodies (mAbs) against DENV have led to the discovery of several novel epitopes on the envelope protein recognized by potent neutralizing mAbs. This information together with in-depth studies on polyclonal sera and B-cells following natural DENV infection has tremendous implications for better immunogen design for a safe and effective dengue vaccine. This review outlines the progress in our understanding of mouse mAbs, human mAbs, and polyclonal sera against DENV envelope and precursor membrane proteins, two surface proteins involved in vaccine development, following natural infection; analyses of these discoveries have provided valuable insight into new strategies involving molecular technology to induce more potent neutralizing antibodies and less enhancing antibodies for next-generation dengue vaccine development.

  19. Production of recombinant dengue non-structural 1 (NS1) proteins from clinical virus isolates.

    Science.gov (United States)

    Yohan, Benediktus; Wardhani, Puspa; Aryati; Trimarsanto, Hidayat; Sasmono, R Tedjo

    2017-01-01

    Dengue is a febrile disease caused by infection of dengue virus (DENV). Early diagnosis of dengue infection is important for better management of the disease. The DENV Non-Structural Protein 1 (NS1) antigen has been routinely used for the early dengue detection. In dengue epidemic countries such as Indonesia, clinicians are increasingly relying on the NS1 detection for confirmation of dengue infection. Various NS1 diagnostic tests are commercially available, however different sensitivities and specificities were observed in various settings. This study was aimed to generate dengue NS1 recombinant protein for the development of dengue diagnostic tests. Four Indonesian DENV isolates were used as the source of the NS1 gene cloning, expression, and purification in bacterial expression system. Recombinant NS1 proteins were successfully purified and their antigenicities were assessed. Immunization of mice with recombinant proteins observed the immunogenicity of the NS1 protein. The generated recombinant proteins can be potentially used in the development of NS1 diagnostic test. With minimal modifications, this method can be used for producing NS1 recombinant proteins from isolates obtained from other geographical regions. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Dengue Virus Specific Immune Response: Implications for laboratory diagnosis and vaccine development

    NARCIS (Netherlands)

    P. Koraka (Penelope)

    2007-01-01

    textabstractDengue viruses (DENV 1-4) belong to the family Flaviviridae, genus Flavivirus. They are transmitted to humans through the bite of infected mosquitoes of the Aedes species. An estimated 100 million people are annually infected with DENV and over two billion people are at risk in

  1. A heparin-functionalized carbon nanotube-based affinity biosensor for dengue virus.

    Science.gov (United States)

    Wasik, Daniel; Mulchandani, Ashok; Yates, Marylynn V

    2017-05-15

    Dengue virus is an arthropod-borne virus transmitted primarily by Aedes mosquitos and is major cause of disease in tropical and subtropical regions. Colloquially known as Dengue Fever, infection can cause hemorrhagic disorders and death in humans and non-human primates. We report a novel electronic biosensor based on a single-walled carbon nanotube network chemiresistive transducer that is functionalized with heparin for low-cost, label-free, ultra-sensitive, and rapid detection of whole dengue virus (DENV). Heparin, an analog of the heparan sulfate proteoglycans that are receptors for dengue virus during infection of Vero cells and hepatocytes, was used for the first time in a biosensor as a biorecognition element instead of traditional antibody. Detection of DENV in viral culture supernatant has similar sensitivity as the corresponding viral titer in phosphate buffer despite the presence of growth media and Vero cell lysate. The biosensor demonstrated sensitivity within the clinically relevant range for humans and infected Aedes aegypti. It has potential application in clinical diagnosis and can improve point-of-care diagnostics of dengue infection. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Dengue Virus and Its Inhibitors: A Brief Review.

    Science.gov (United States)

    Tian, Yu-Shi; Zhou, Yi; Takagi, Tatsuya; Kameoka, Masanori; Kawashita, Norihito

    2018-01-01

    The global occurrence of viral infectious diseases poses a significant threat to human health. Dengue virus (DENV) infection is one of the most noteworthy of these infections. According to a WHO survey, approximately 400 million people are infected annually; symptoms deteriorate in approximately one percent of cases. Numerous foundational and clinical investigations on viral epidemiology, structure and function analysis, infection source and route, therapeutic targets, vaccines, and therapeutic drugs have been conducted by both academic and industrial researchers. At present, CYD-TDV or Dengvaxia ® is the only approved vaccine, but potent inhibitors are currently under development. In this review, an overview of the viral life circle and the history of DENVs is presented, and the most recently reported antiviral candidates and newly discovered promising targets are focused and summarized. We believe that these successes and failures have enabled progress in anti-DENV drug discovery and hope that our review will stimulate further innovation in this area.

  3. A three year retrospective study on the increasing trend in seroprevalence of dengue infection from southern Odisha, India

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    Sanghamitra Padhi

    2014-01-01

    Full Text Available Background & objectives: In Odisha, several cases of dengue virus infection were detected for the first time in 2010, the importance of dengue as a serious mosquito-borne viral infection was felt only in 2011 with the reporting of many more positive cases. This retrospective three year study was done to find out the seroprevalence of dengue Ig m0 antibody and to know the predominant serotype of dengue virus among the patients suspected to have dengue virus infection in a tertiary care hospital in southern Odisha, India. Methods: Blood samples from clinically suspected dengue cases admitted in the Medicine and Paediatrics departments of a tertiary care hospital were collected. These were processed for detection of dengue specific IgM antibody, carried out by the ELISA method. Dengue IgM antibody positive serum samples were tested for serotypic identification. Results: o0 f the 5102 samples tested, 1074 (21.05 % were positive for dengue IgM. Maximum numbers of cases were found in 2012. Majority (47.86 % of cases were detected in the month of September. The most common affected age group was 11 to 20 yr. DENV1 and DENV2 were the detected serotypes. Interpretation & conclusions: Rapid increase in the dengue cases in 2012 became a public health concern as majority of cases were affecting the young adolescents. Most of the cases were reported in post-monsoon period indicating a need for acceleration of vector control programmes prior to arrival of monsoon.

  4. Simultaneous circulation of genotypes I and III of dengue virus 3 in Colombia

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    Domingo Cristina

    2008-09-01

    Full Text Available Abstract Background Dengue is a major health problem in tropical and subtropical regions. In Colombia, dengue viruses (DENV cause about 50,000 cases annually, 10% of which involve Dengue Haemorrhagic Fever/Dengue Shock Syndrome. The picture is similar in other surrounding countries in the Americas, with recent outbreaks of severe disease, mostly associated with DENV serotype 3, strains of the Indian genotype, introduced into the Americas in 1994. Results The analysis of the 3'end (224 bp of the envelope gene from 32 DENV-3 strains recently recovered in Colombia confirms the circulation of the Indian genotype, and surprisingly the co-circulation of an Asian-Pacific genotype only recently described in the Americas. Conclusion These results have important implications for epidemiology and surveillance of DENV infection in Central and South America. Molecular surveillance of the DENV genotypes infecting humans could be a very valuable tool for controlling/mitigating the impact of the DENV infection.

  5. Deeper understanding about the genetic structure of dengue virus using SVM

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    Choi Subin

    2016-01-01

    Full Text Available Dengue fever, mainly found in the tropical and subtropical regions, is carried by mosquitoes. With the help of greenhouse effect, places considered to be a Dengue safe-zone are becoming more and more dangerous. Dengue fever shows similar aspects to MERS, which caused heavy casualties in South Korea; Dengue virus does not have clear treatments nor vaccines like MERS. Development of Dengue vaccine is actively investigated lately. However, it is not easy to succeed; the fact that Dengue’s 4 serotypes have different properties and that repeated infections worsen the symptoms. This research aims to analyze the 4 serotypes (DENV1, DENV2, DENV3, DENV4 using SVM and ANN algorithms to investigate the constraints in the development of Dengue’s vaccines and treatments.

  6. Treatment model of dengue hemorrhagic fever infection in human body

    Science.gov (United States)

    Handayani, D.; Nuraini, N.; Primasari, N.; Wijaya, K. P.

    2014-03-01

    The treatment model of DHF presented in this paper involves the dynamic of five time-dependent compartments, i.e. susceptible, infected, free virus particle, immune cell, and haematocrit level. The treatment model is investigated based on normalization of haematocrit level, which is expressed as intravenous fluid infusion control. We analyze the stability of the disease free equilibrium and the endemic equilibrium. The numerical simulations will explain the dynamic of each compartment in human body. These results show particularly that infected compartment and free virus particle compartment are tend to be vanished in two weeks after the onset of dengue virus. However, these simulation results also show that without the treatment, the haematocrit level will decrease even though not up to the normal level. Therefore the effective haematocrit normalization should be done with the treatment control.

  7. Detection of micro RNA hsa-let-7e in peripheral blood mononuclear cells infected with dengue virus serotype-2: preliminary study

    Science.gov (United States)

    Masyeni, S.; Hadi, U.; Kuntaman; Yohan, B.; Margyaningsih, N. I.; Sasmono, R. T.

    2018-03-01

    Pathogenesis of dengue infection is still obscure. Recently, the role of microRNA has been associated with the cytokine storm which leads to plasma leakage in endothelial cells. The objective of our study was to determine whether particular microRNA is overexpressed in PBMCs infected with DENV and to assess its correlation to the expression of suppressor of cytokine signaling 3 (SOCS3) proteins to increase the production of pro-inflammatory cytokines. We report the result of a preliminary study on the expression of microRNA hsa-let-7e. The peripheral blood mononuclear cells (PBMCs) from the healthy volunteer were infected with the clinical isolate of DENV-2. RNA was extracted with miRCURYLNATMExiqon. Quantitative Real-Time PCR was used to measure the relative expression of hsa-let-7e micro RNA and the mRNA of SOCS3 proteins. MicroRNA hsa-let-7e expression was increased in PBMCs upon DENV-2 infection. The relative expression of hsa-let-7e is detected at 1.46 folds relative to uninfected PBMCs in 4 hours post-infection and decreased in 19 hours post infection. In contrast, the expression of mRNA of SOCS3 was inversely expressed with hsa-let-7 expression. MicroRNA was overexpressed in PBMCs upon infection with DENV-2. This microRNA may bind the SOCS3 and contribute to the pathogenesis of dengue infection.

  8. Detection of Hepatitis C Virus Coinfection in Patients with Dengue Diagnosis

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    Carlos Machain-Williams

    2014-01-01

    Full Text Available Coinfection produced by dengue virus (DENV and hepatitis C virus (HCV is a serious problem of public health in Mexico, as they both circulate in tropical zones and may lead to masking or complicating symptoms. In this research, we detected active coinfected patients by HCV residing in the endemic city of Mérida, Yucatán, Mexico, with positive diagnosis to dengue during the acute phase. We performed a retrospective analysis of 240 serum samples from dengue patients. The IgM-ELISA serological test was used for dengue diagnosis, as well as viral isolation to confirm infection. DENV and HCV were detected by RT-PCR. Thus, 31 (12.9% samples showed DENV-HCV coinfection, but interestingly the highest frequency of coinfection cases was found in male patients presenting hemorrhagic dengue in 19/31 (61.29%, with a predominance of 12 : 7 in males. Firstly, coinfection of DENV-HCV in Mérida, Mexico, was detected in young dengue patients, between 11 and 20 years old (38.7%, followed by those between 21 and 30 years old (32%; only 16.13% were between 0 and 10 years of age. Diagnosis of HCV infection in patients with dengue is highly recommended in order to establish potential risk in clinical manifestations as well as dictate patients' special care.

  9. Comparison of real-time SYBR green dengue assay with real-time taqman RT-PCR dengue assay and the conventional nested PCR for diagnosis of primary and secondary dengue infection

    Science.gov (United States)

    Paudel, Damodar; Jarman, Richard; Limkittikul, Kriengsak; Klungthong, Chonticha; Chamnanchanunt, Supat; Nisalak, Ananda; Gibbons, Robert; Chokejindachai, Watcharee

    2011-01-01

    Background: Dengue fever and dengue hemorrhagic fever are caused by dengue virus. Dengue infection remains a burning problem of many countries. To diagnose acute dengue in the early phase we improve the low cost, rapid SYBR green real time assay and compared the sensitivity and specificity with real time Taqman® assay and conventional nested PCR assay. Aims: To develop low cost, rapid and reliable real time SYBR green diagnostic dengue assay and compare with Taqman real-time assay and conventional nested PCR (modified Lanciotti). Materials and Methods: Eight cultured virus strains were diluted in tenth dilution down to undetectable level by the PCR to optimize the primer, temperature (annealing, and extension and to detect the limit of detection of the assay. Hundred and ninety three ELISA and PCR proved dengue clinical samples were tested with real time SYBR® Green assay, real time Taqman® assay to compare the sensitivity and specificity. Results: Sensitivity and specificity of real time SYBR® green dengue assay (84% and 66%, respectively) was almost comparable to those (81% and 74%) of Taqman real time PCR dengue assay. Real time SYBR® green RT-PCR was equally sensitive in primary and secondary infection while real time Taqman was less sensitive in the secondary infection. Sensitivity of real time Taqman on DENV3 (87%) was equal to SYBR green real time PCR dengue assay. Conclusion: We developed low cost rapid diagnostic SYBR green dengue assay. Further study is needed to make duplex primer assay for the serotyping of dengue virus. PMID:22363089

  10. Development, characterization and application of monoclonal antibodies against Brazilian Dengue virus isolates.

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    Camila Zanluca

    Full Text Available Dengue is the most prevalent human arboviral disease. The morbidity related to dengue infection supports the need for an early, quick and effective diagnostic test. Brazil is a hotspot for dengue, but no serological diagnostic test has been produced using Brazilian dengue virus isolates. This study aims to improve the development of immunodiagnostic methods for dengue virus (DENV detection through the production and characterization of 22 monoclonal antibodies (mAbs against Brazilian isolates of DENV-1, -2 and -3. The mAbs include IgG2bκ, IgG2aκ and IgG1κ isotypes, and most were raised against the envelope or the pre-membrane proteins of DENV. When the antibodies were tested against the four DENV serotypes, different reactivity patterns were identified: group-specific, subcomplex specific (DENV-1, -3 and -4 and DENV-2 and -3 and dengue serotype-specific (DENV-2 or -3. Additionally, some mAbs cross-reacted with yellow fever virus (YFV, West Nile virus (WNV and Saint Louis encephalitis virus (SLEV. None of the mAbs recognized the alphavirus Venezuelan equine encephalitis virus (VEEV. Furthermore, mAbs D3 424/8G, D1 606/A12/B9 and D1 695/12C/2H were used to develop a capture enzyme-linked immunosorbent assay (ELISA for anti-dengue IgM detection in sera from patients with acute dengue. To our knowledge, these are the first monoclonal antibodies raised against Brazilian DENV isolates, and they may be of special interest in the development of diagnostic assays, as well as for basic research.

  11. A Rapid and Improved Method to Generate Recombinant Dengue Virus Vaccine Candidates.

    Science.gov (United States)

    Govindarajan, Dhanasekaran; Guan, Liming; Meschino, Steven; Fridman, Arthur; Bagchi, Ansu; Pak, Irene; ter Meulen, Jan; Casimiro, Danilo R; Bett, Andrew J

    2016-01-01

    Dengue is one of the most important mosquito-borne infections accounting for severe morbidity and mortality worldwide. Recently, the tetravalent chimeric live attenuated Dengue vaccine Dengvaxia® was approved for use in several dengue endemic countries. In general, live attenuated vaccines (LAV) are very efficacious and offer long-lasting immunity against virus-induced disease. Rationally designed LAVs can be generated through reverse genetics technology, a method of generating infectious recombinant viruses from full length cDNA contained in bacterial plasmids. In vitro transcribed (IVT) viral RNA from these infectious clones is transfected into susceptible cells to generate recombinant virus. However, the generation of full-length dengue virus cDNA clones can be difficult due to the genetic instability of viral sequences in bacterial plasmids. To circumvent the need for a single plasmid containing a full length cDNA, in vitro ligation of two or three cDNA fragments contained in separate plasmids can be used to generate a full-length dengue viral cDNA template. However, in vitro ligation of multiple fragments often yields low quality template for IVT reactions, resulting in inconsistent low yield RNA. These technical difficulties make recombinant virus recovery less efficient. In this study, we describe a simple, rapid and efficient method of using LONG-PCR to recover recombinant chimeric Yellow fever dengue (CYD) viruses as potential dengue vaccine candidates. Using this method, we were able to efficiently generate several viable recombinant viruses without introducing any artificial mutations into the viral genomes. We believe that the techniques reported here will enable rapid and efficient recovery of recombinant flaviviruses for evaluation as vaccine candidates and, be applicable to the recovery of other RNA viruses.

  12. A Rapid and Improved Method to Generate Recombinant Dengue Virus Vaccine Candidates.

    Directory of Open Access Journals (Sweden)

    Dhanasekaran Govindarajan

    Full Text Available Dengue is one of the most important mosquito-borne infections accounting for severe morbidity and mortality worldwide. Recently, the tetravalent chimeric live attenuated Dengue vaccine Dengvaxia® was approved for use in several dengue endemic countries. In general, live attenuated vaccines (LAV are very efficacious and offer long-lasting immunity against virus-induced disease. Rationally designed LAVs can be generated through reverse genetics technology, a method of generating infectious recombinant viruses from full length cDNA contained in bacterial plasmids. In vitro transcribed (IVT viral RNA from these infectious clones is transfected into susceptible cells to generate recombinant virus. However, the generation of full-length dengue virus cDNA clones can be difficult due to the genetic instability of viral sequences in bacterial plasmids. To circumvent the need for a single plasmid containing a full length cDNA, in vitro ligation of two or three cDNA fragments contained in separate plasmids can be used to generate a full-length dengue viral cDNA template. However, in vitro ligation of multiple fragments often yields low quality template for IVT reactions, resulting in inconsistent low yield RNA. These technical difficulties make recombinant virus recovery less efficient. In this study, we describe a simple, rapid and efficient method of using LONG-PCR to recover recombinant chimeric Yellow fever dengue (CYD viruses as potential dengue vaccine candidates. Using this method, we were able to efficiently generate several viable recombinant viruses without introducing any artificial mutations into the viral genomes. We believe that the techniques reported here will enable rapid and efficient recovery of recombinant flaviviruses for evaluation as vaccine candidates and, be applicable to the recovery of other RNA viruses.

  13. The dengue virus type 2 envelope protein fusion peptide is essential for membrane fusion

    International Nuclear Information System (INIS)

    Huang, Claire Y.-H.; Butrapet, Siritorn; Moss, Kelly J.; Childers, Thomas; Erb, Steven M.; Calvert, Amanda E.; Silengo, Shawn J.; Kinney, Richard M.; Blair, Carol D.; Roehrig, John T.

    2010-01-01

    The flaviviral envelope (E) protein directs virus-mediated membrane fusion. To investigate membrane fusion as a requirement for virus growth, we introduced 27 unique mutations into the fusion peptide of an infectious cDNA clone of dengue 2 virus and recovered seven stable mutant viruses. The fusion efficiency of the mutants was impaired, demonstrating for the first time the requirement for specific FP AAs in optimal fusion. Mutant viruses exhibited different growth kinetics and/or genetic stabilities in different cell types and adult mosquitoes. Virus particles could be recovered following RNA transfection of cells with four lethal mutants; however, recovered viruses could not re-infect cells. These viruses could enter cells, but internalized virus appeared to be retained in endosomal compartments of infected cells, thus suggesting a fusion blockade. Mutations of the FP also resulted in reduced virus reactivity with flavivirus group-reactive antibodies, confirming earlier reports using virus-like particles.

  14. Purification and crystallization of dengue and West Nile virus NS2B–NS3 complexes

    Energy Technology Data Exchange (ETDEWEB)

    D’Arcy, Allan, E-mail: allan.darcy@novartis.com; Chaillet, Maxime; Schiering, Nikolaus; Villard, Frederic [Novartis Institutes of Biomedical Research, Protease Platform, Klybeckstrasse 144, CH 4002 Basel (Switzerland); Lim, Siew Pheng [Novartis Institutes of Tropical Diseases (Singapore); Lefeuvre, Peggy [Novartis Institutes of Biomedical Research, Protease Platform, Klybeckstrasse 144, CH 4002 Basel (Switzerland); Erbel, Paul [Novartis Institutes of Biomedical Research, Protease Platform, Klybeckstrasse 144, CH 4002 Basel (Switzerland); Novartis Institutes of Tropical Diseases (Singapore)

    2006-02-01

    Crystals of dengue serotype 2 and West Nile virus NS2B–NS3 protease complexes have been obtained and the crystals of both diffract to useful resolution. Sample homogeneity was essential for obtaining X-ray-quality crystals of the dengue protease. Controlled proteolysis produced a crystallizable fragment of the apo West Nile virus NS2B–NS3 and crystals were also obtained in the presence of a peptidic inhibitor. Both dengue and West Nile virus infections are an increasing risk to humans, not only in tropical and subtropical areas, but also in North America and parts of Europe. These viral infections are generally transmitted by mosquitoes, but may also be tick-borne. Infection usually results in mild flu-like symptoms, but can also cause encephalitis and fatalities. Approximately 2799 severe West Nile virus cases were reported this year in the United States, resulting in 102 fatalities. With this alarming increase in the number of West Nile virus infections in western countries and the fact that dengue virus already affects millions of people per year in tropical and subtropical climates, there is a real need for effective medicines. A possible therapeutic target to combat these viruses is the protease, which is essential for virus replication. In order to provide structural information to help to guide a lead identification and optimization program, crystallizations of the NS2B–NS3 protease complexes from both dengue and West Nile viruses have been initiated. Crystals that diffract to high resolution, suitable for three-dimensional structure determinations, have been obtained.

  15. Purification and crystallization of dengue and West Nile virus NS2B–NS3 complexes

    International Nuclear Information System (INIS)

    D’Arcy, Allan; Chaillet, Maxime; Schiering, Nikolaus; Villard, Frederic; Lim, Siew Pheng; Lefeuvre, Peggy; Erbel, Paul

    2006-01-01

    Crystals of dengue serotype 2 and West Nile virus NS2B–NS3 protease complexes have been obtained and the crystals of both diffract to useful resolution. Sample homogeneity was essential for obtaining X-ray-quality crystals of the dengue protease. Controlled proteolysis produced a crystallizable fragment of the apo West Nile virus NS2B–NS3 and crystals were also obtained in the presence of a peptidic inhibitor. Both dengue and West Nile virus infections are an increasing risk to humans, not only in tropical and subtropical areas, but also in North America and parts of Europe. These viral infections are generally transmitted by mosquitoes, but may also be tick-borne. Infection usually results in mild flu-like symptoms, but can also cause encephalitis and fatalities. Approximately 2799 severe West Nile virus cases were reported this year in the United States, resulting in 102 fatalities. With this alarming increase in the number of West Nile virus infections in western countries and the fact that dengue virus already affects millions of people per year in tropical and subtropical climates, there is a real need for effective medicines. A possible therapeutic target to combat these viruses is the protease, which is essential for virus replication. In order to provide structural information to help to guide a lead identification and optimization program, crystallizations of the NS2B–NS3 protease complexes from both dengue and West Nile viruses have been initiated. Crystals that diffract to high resolution, suitable for three-dimensional structure determinations, have been obtained

  16. Satellite based hydroclimatic understanding of evolution of Dengue and Zika virus

    Science.gov (United States)

    Khan, R.; Jutla, A.; Colwell, R. R.

    2017-12-01

    Vector-borne diseases are prevalent in tropical and subtropical regions especially in Africa, South America, and Asia. Vector eradication is perhaps not possible since pathogens adapt to local environment. In absence of appropriate vaccinations for Dengue and Zika virus, burden of these two infections continue to increase in several geographical locations. Aedes spp. is one of the major vectors for Dengue and Zika viruses. Etiologies on Dengue and Zika viruses are evolving, however the key question remains as to how one species of mosquito can transmit two different infections? We argue that a set of conducive environmental condition, modulated by regional climatic and weather processes, may lead to abundance of a specific virus. Using satellite based rainfall (TRMM/GPM), land surface temperature (MODIS) and dew point temperature (AIRS/MERRA), we have identified appropriate thresholds that can provide estimate on risk of abundance of Dengue or Zika viruses at least few weeks in advance. We will discuss a framework coupling satellite derived hydroclimatic and societal processes to predict environmental niches of favorability of conditions of Dengue or Zika risk in human population on a global scale.

  17. Estimates of dengue force of infection in children in Colombo, Sri Lanka.

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    Clarence C Tam

    Full Text Available Dengue is the most important vector-borne viral disease worldwide and a major cause of childhood fever burden in Sri Lanka, which has experienced a number of large epidemics in the past decade. Despite this, data on the burden and transmission of dengue virus in the Indian Subcontinent are lacking. As part of a longitudinal fever surveillance study, we conducted a dengue seroprevalence survey among children aged <12 years in Colombo, Sri Lanka. We used a catalytic model to estimate the risk of primary infection among seronegative children. Over 50% of children had IgG antibodies to dengue virus and seroprevalence increased with age. The risk of primary infection was 14.1% per year (95% CI: 12.7%-15.6%, indicating that among initially seronegative children, approximately 1 in 7 experience their first infection within 12 months. There was weak evidence to suggest that the force of primary infection could be lower for children aged 6 years and above. We estimate that there are approximately 30 primary dengue infections among children <12 years in the community for every case notified to national surveillance, although this ratio is closer to 100:1 among infants. Dengue represents a considerable infection burden among children in urban Sri Lanka, with levels of transmission comparable to those in the more established epidemics of Southeast Asia.

  18. Imported dengue virus serotype 1 from Madeira to Finland 2012.

    Science.gov (United States)

    Huhtamo, E; Korhonen, Em; Vapalahti, O

    2013-02-21

    Imported dengue cases originating from the Madeiran outbreak are increasingly reported. In 2012 five Finnish travellers returning from Madeira were diagnosed with dengue fever. Viral sequence data was obtained from two patients. The partial C-preM sequences (399 and 396 bp respectively) were found similar to that of an autochthonous case from Madeira. The partial E-gene sequence (933 bp) which was identical among the two patients grouped phylogenetically with South American strains of dengue virus serotype 1.

  19. Perturbed cholesterol and vesicular trafficking associated with dengue blocking in Wolbachia-infected Aedes aegypti cells.

    Science.gov (United States)

    Geoghegan, Vincent; Stainton, Kirsty; Rainey, Stephanie M; Ant, Thomas H; Dowle, Adam A; Larson, Tony; Hester, Svenja; Charles, Philip D; Thomas, Benjamin; Sinkins, Steven P

    2017-09-13

    Wolbachia are intracellular maternally inherited bacteria that can spread through insect populations and block virus transmission by mosquitoes, providing an important approach to dengue control. To better understand the mechanisms of virus inhibition, we here perform proteomic quantification of the effects of Wolbachia in Aedes aegypti mosquito cells and midgut. Perturbations are observed in vesicular trafficking, lipid metabolism and in the endoplasmic reticulum that could impact viral entry and replication. Wolbachia-infected cells display a differential cholesterol profile, including elevated levels of esterified cholesterol, that is consistent with perturbed intracellular cholesterol trafficking. Cyclodextrins have been shown to reverse lipid accumulation defects in cells with disrupted cholesterol homeostasis. Treatment of Wolbachia-infected Ae. aegypti cells with 2-hydroxypropyl-β-cyclodextrin restores dengue replication in Wolbachia-carrying cells, suggesting dengue is inhibited in Wolbachia-infected cells by localised cholesterol accumulation. These results demonstrate parallels between the cellular Wolbachia viral inhibition phenotype and lipid storage genetic disorders. Wolbachia infection of mosquitoes can block dengue virus infection and is tested in field trials, but the mechanism of action is unclear. Using proteomics, Geoghegan et al. here identify effects of Wolbachia on cholesterol homeostasis and dengue virus replication in Aedes aegypti.

  20. Stability Analysis Susceptible, Exposed, Infected, Recovered (SEIR) Model for Spread Model for Spread of Dengue Fever in Medan

    Science.gov (United States)

    Side, Syafruddin; Molliq Rangkuti, Yulita; Gerhana Pane, Dian; Setia Sinaga, Marlina

    2018-01-01

    Dengue fever is endemic disease which spread through vector, Aedes Aegypty. This disease is found more than 100 countries, such as, United State, Africa as well Asia, especially in country that have tropic climate. Mathematical modeling in this paper, discusses the speed of the spread of dengue fever. The model adopting divided over four classes, such as Susceptible (S), Exposed (E), Infected (I) and Recovered (R). SEIR model further analyzed to detect the re-breeding value based on the number reported case by dengue in Medan city. Analysis of the stability of the system in this study is asymptotically stable indicating a case of endemic and unstable that show cases the endemic cases. Simulation on the mathematical model of SEIR showed that require a very long time to produce infected humans will be free of dengue virus infection. This happens because of dengue virus infection that occurs continuously between human and vector populations.

  1. Diagnosis of Dengue Infection Using Conventional and Biosensor Based Techniques

    Science.gov (United States)

    Parkash, Om; Hanim Shueb, Rafidah

    2015-01-01

    Dengue is an arthropod-borne viral disease caused by four antigenically different serotypes of dengue virus. This disease is considered as a major public health concern around the world. Currently, there is no licensed vaccine or antiviral drug available for the prevention and treatment of dengue disease. Moreover, clinical features of dengue are indistinguishable from other infectious diseases such as malaria, chikungunya, rickettsia and leptospira. Therefore, prompt and accurate laboratory diagnostic test is urgently required for disease confirmation and patient triage. The traditional diagnostic techniques for the dengue virus are viral detection in cell culture, serological testing, and RNA amplification using reverse transcriptase PCR. This paper discusses the conventional laboratory methods used for the diagnosis of dengue during the acute and convalescent phase and highlights the advantages and limitations of these routine laboratory tests. Subsequently, the biosensor based assays developed using various transducers for the detection of dengue are also reviewed. PMID:26492265

  2. Luteolin restricts dengue virus replication through inhibition of the proprotein convertase furin.

    Science.gov (United States)

    Peng, Minhua; Watanabe, Satoru; Chan, Kitti Wing Ki; He, Qiuyan; Zhao, Ya; Zhang, Zhongde; Lai, Xiaoping; Luo, Dahai; Vasudevan, Subhash G; Li, Geng

    2017-07-01

    In many countries afflicted with dengue fever, traditional medicines are widely used as panaceas for illness, and here we describe the systematic evaluation of a widely known natural product, luteolin, originating from the "heat clearing" class of herbs. We show that luteolin inhibits the replication of all four serotypes of dengue virus, but the selectivity of the inhibition was weak. In addition, ADE-mediated dengue virus infection of human cell lines and primary PBMCs was inhibited. In a time-of-drug-addition study, luteolin was found to reduce infectious virus particle formation, but not viral RNA synthesis, in Huh-7 cells. During the virus life cycle, the host protease furin cleaves the pr moiety from prM protein of immature virus particles in the trans-Golgi network to produce mature virions. Analysis of virus particles from luteolin-treated cells revealed that prM was not cleaved efficiently. Biochemical interrogation of human furin showed that luteolin inhibited the enzyme activity in an uncompetitive manner, with Ki value of 58.6 μM, suggesting that treatment may restrict the virion maturation process. Luteolin also exhibited in vivo antiviral activity in mice infected with DENV, causing reduced viremia. Given the mode of action of luteolin and its widespread source, it is possible that it can be tested in combination with other dengue virus inhibitors. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Dengue-associated kidney disease.

    Science.gov (United States)

    Lizarraga, Karlo J; Nayer, Ali

    2014-01-01

    A mosquito-borne viral illness highly prevalent in the tropics and subtropics, dengue is considered a major global health threat by the World Health Organization. Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO) and Web of Science have been searched. An RNA virus from the genus Flavivirus, dengue virus is transmitted by Aedes aegypti,the yellow fever mosquito. Dengue is asymptomatic in as many as one half of infected individuals. Dengue fever is an acute febrile illness accompanied by constitutional symptoms. Dengue hemorrhagic fever and dengue shock syndrome are the severe forms of dengue infection.Dengue infection has been associated with a variety of renal disorders. Acute renal failure is a potential complication of severe dengue infection and is typically associated with hypotension, rhabdomyolysis, or hemolysis. Acute renal failure complicates severe dengue infection in 2-5% of the cases and carries a high mortality rate. Proteinuria has been detected in as high as 74% of patients with severe dengue infection. Hematuria has been reported in up to 12.5% of patients. Various types of glomerulonephritis have been reported during or shortly after dengue infection in humans and mouse models of dengue infection. Mesangial proliferation and immune complex deposition are the dominant histologic features of dengue-associated glomerulonephritis. On a rare occasion, dengue infection is associated with systemic autoimmune disorders involving the kidneys. In the vast majority of cases, dengue infection and associated renal disorders are self-limited.

  4. A small molecule fusion inhibitor of dengue virus.

    Science.gov (United States)

    Poh, Mee Kian; Yip, Andy; Zhang, Summer; Priestle, John P; Ma, Ngai Ling; Smit, Jolanda M; Wilschut, Jan; Shi, Pei-Yong; Wenk, Markus R; Schul, Wouter

    2009-12-01

    The dengue virus envelope protein plays an essential role in viral entry by mediating fusion between the viral and host membranes. The crystal structure of the envelope protein shows a pocket (located at a "hinge" between Domains I and II) that can be occupied by ligand n-octyl-beta-D-glucoside (betaOG). Compounds blocking the betaOG pocket are thought to interfere with conformational changes in the envelope protein that are essential for fusion. Two fusion assays were developed to examine the anti-fusion activities of compounds. The first assay measures the cellular internalization of propidium iodide upon membrane fusion. The second assay measures the protease activity of trypsin upon fusion between dengue virions and trypsin-containing liposomes. We performed an in silico virtual screening for small molecules that can potentially bind to the betaOG pocket and tested these candidate molecules in the two fusion assays. We identified one compound that inhibits dengue fusion in both assays with an IC(50) of 6.8 microM and reduces viral titers with an EC(50) of 9.8 microM. Time-of-addition experiments showed that the compound was only active when present during viral infection but not when added 1h later, in agreement with a mechanism of action through fusion inhibition.

  5. Emergence of Dengue virus serotype 3 on Mayotte Island, Indian ...

    African Journals Online (AJOL)

    A serosurvey carried out in 2006 in Mayotte, a French overseas collectivity in the Indian Ocean, confirmed previous circulation of dengue virus (DENV) on the island, but since the set up of a laboratory-based surveillance of dengue-like illness in 2007, no case of DENV has been confirmed. In response to an outbreak of ...

  6. Dengue virus exposure among blood donors in Ghana | Narkwa ...

    African Journals Online (AJOL)

    Dengue is an urban arbovirus whose aetiologic agent is the flavivirus with four distinct antigen serotypes (DENV-1, DENV-2, DENV-3 and DENV-4) that is transmitted to humans through the bite of the mosquito Aedes aegypti. Ghana is endemic for Aedes aegypti mosquitoes and probably dengue viruses. Due to limited data ...

  7. The spatial dynamics of dengue virus in Kamphaeng Phet, Thailand.

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    Piraya Bhoomiboonchoo

    2014-09-01

    Full Text Available Dengue is endemic to the rural province of Kamphaeng Phet, Northern Thailand. A decade of prospective cohort studies has provided important insights into the dengue viruses and their generated disease. However, as elsewhere, spatial dynamics of the pathogen remain poorly understood. In particular, the spatial scale of transmission and the scale of clustering are poorly characterized. This information is critical for effective deployment of spatially targeted interventions and for understanding the mechanisms that drive the dispersal of the virus.We geocoded the home locations of 4,768 confirmed dengue cases admitted to the main hospital in Kamphaeng Phet province between 1994 and 2008. We used the phi clustering statistic to characterize short-term spatial dependence between cases. Further, to see if clustering of cases led to similar temporal patterns of disease across villages, we calculated the correlation in the long-term epidemic curves between communities. We found that cases were 2.9 times (95% confidence interval 2.7-3.2 more likely to live in the same village and be infected within the same month than expected given the underlying spatial and temporal distribution of cases. This fell to 1.4 times (1.2-1.7 for individuals living in villages 1 km apart. Significant clustering was observed up to 5 km. We found a steadily decreasing trend in the correlation in epidemics curves by distance: communities separated by up to 5 km had a mean correlation of 0.28 falling to 0.16 for communities separated between 20 km and 25 km. A potential explanation for these patterns is a role for human movement in spreading the pathogen between communities. Gravity style models, which attempt to capture population movement, outperformed competing models in describing the observed correlations.There exists significant short-term clustering of cases within individual villages. Effective spatially and temporally targeted interventions deployed within villages may

  8. Dengue infection and miscarriage: a prospective case control study.

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    Peng Chiong Tan

    Full Text Available BACKGROUND: Dengue is the most prevalent mosquito borne infection worldwide. Vertical transmissions after maternal dengue infection to the fetus and pregnancy losses in relation to dengue illness have been reported. The relationship of dengue to miscarriage is not known. METHOD: We aimed to establish the relationship of recent dengue infection and miscarriage. Women who presented with miscarriage (up to 22 weeks gestation to our hospital were approached to participate in the study. For each case of miscarriage, we recruited 3 controls with viable pregnancies at a similar gestation. A brief questionnaire on recent febrile illness and prior dengue infection was answered. Blood was drawn from participants, processed and the frozen serum was stored. Stored sera were thawed and then tested in batches with dengue specific IgM capture ELISA, dengue non-structural protein 1 (NS1 antigen and dengue specific IgG ELISA tests. Controls remained in the analysis if their pregnancies continued beyond 22 weeks gestation. Tests were run on 116 case and 341 control sera. One case (a misdiagnosed viable early pregnancy plus 45 controls (39 lost to follow up and six subsequent late miscarriages were excluded from analysis. FINDINGS: Dengue specific IgM or dengue NS1 antigen (indicating recent dengue infection was positive in 6/115 (5·2% cases and 5/296 (1·7% controls RR 3·1 (95% CI 1·0-10 P = 0·047. Maternal age, gestational age, parity and ethnicity were dissimilar between cases and controls. After adjustments for these factors, recent dengue infection remained significantly more frequently detected in cases than controls (AOR 4·2 95% CI 1·2-14 P = 0·023. INTERPRETATION: Recent dengue infections were more frequently detected in women presenting with miscarriage than in controls whose pregnancies were viable. After adjustments for confounders, the positive association remained.

  9. Dengue viral infections in Pakistan and other Asian countries: a comprehensive review.

    Science.gov (United States)

    Zubair, Muhammad; Ashraf, Muhammad; Ahsan, Aitezaz; Nazir, Noor-Ul-Ain; Hanif, Hina; Khan, Haider Ali

    2016-07-01

    Infections due to Dengue virus are widespread throughout the world. Disease starts with mild flu like sickness to a severe intricate condition which results in the death of the patient. Dengue illness has high morbidity and mortality in Pakistan as well as in other Asian countries. The Review article is a discourse analysis that explores the facts about the history, emergence and impact of dengue in Pakistan and other Asian countries. Data was collected from internet sources, mainly using Science Direct and PubMed. The final literature was reviewed and summarised. About 150 articles were identified and 47 articles were shortlisted for final review. Aedesaegypti was found to be a major vector for the transmission and spread of dengue illness. Treatment comprises supportive therapy as no specific treatment was available. During the last couple of years, the incidence of dengue fever was extraordinary in metropolitan cities of Pakistan.

  10. Diabetes Mellitus Increases Severity of Thrombocytopenia in Dengue-Infected Patients

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    Chung-Yuan Chen

    2015-02-01

    Full Text Available Background: Diabetes mellitus is known to exacerbate bacterial infection, but its effect on the severity of viral infection has not been well studied. The severity of thrombocytopenia is an indicator of the severity of dengue virus infection. We investigated whether diabetes is associated with thrombocytopenia in dengue-infected patients. Methods: We studied clinical characteristics of 644 patients with dengue infection at a university hospital during the epidemic on 1 June 2002 to 31 December 2002 in Taiwan. Platelet counts and biochemical data were compared between patients with and without diabetes. Potential risk factors associated with thrombocytopenia were explored using regression analyses. Results: Dengue-infected patients with diabetes had lower platelet counts than patients without diabetes during the first three days (54.54 ± 51.69 vs. 86.58 ± 63.4 (p ≤ 0.001, 43.98 ± 44.09 vs. 64.52 ± 45.06 (p = 0.002, 43.86 ± 35.75 vs. 62.72 ± 51.2 (p = 0.012. Diabetes mellitus, death, dengue shock syndrome (DSS and dengue hemorrhagic fever (DHF and increased glutamic-pyruvate transaminase (GPT levels were significantly associated with lower platelet counts during the first day of hospitalization for dengue fever with regression β of −13.981 (95% confidence interval (CI −27.587, −0.374, −26.847 (95% CI −37.562, −16.132, and 0.054 (95% CI 0.015, 0.094 respectively. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients with or without diabetes with regression β of −2.947 (p = 0.004, 2.801 (p = 0.005, and −3.568 (p ≤ 0.001, respectively. Diabetic patients with dengue had a higher rate of dengue hemorrhagic fever (DHF/dengue shock syndrome (DSS than non-diabetic patients. They also had lower blood albumin, were older, and higher triglyceride levels. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in

  11. Diabetes mellitus increases severity of thrombocytopenia in dengue-infected patients.

    Science.gov (United States)

    Chen, Chung-Yuan; Lee, Mei-Yueh; Lin, Kun-Der; Hsu, Wei-Hao; Lee, Yaun-Jinn; Hsiao, Pi-Jung; Shin, Shyi-Jang

    2015-02-10

    Diabetes mellitus is known to exacerbate bacterial infection, but its effect on the severity of viral infection has not been well studied. The severity of thrombocytopenia is an indicator of the severity of dengue virus infection. We investigated whether diabetes is associated with thrombocytopenia in dengue-infected patients. We studied clinical characteristics of 644 patients with dengue infection at a university hospital during the epidemic on 1 June 2002 to 31 December 2002 in Taiwan. Platelet counts and biochemical data were compared between patients with and without diabetes. Potential risk factors associated with thrombocytopenia were explored using regression analyses. Dengue-infected patients with diabetes had lower platelet counts than patients without diabetes during the first three days (54.54±51.69 vs. 86.58±63.4 (p≤0.001), 43.98±44.09 vs. 64.52±45.06 (p=0.002), 43.86±35.75 vs. 62.72±51.2 (p=0.012)). Diabetes mellitus, death, dengue shock syndrome (DSS) and dengue hemorrhagic fever (DHF) and increased glutamic-pyruvate transaminase (GPT) levels were significantly associated with lower platelet counts during the first day of hospitalization for dengue fever with regression β of -13.981 (95% confidence interval (CI) -27.587, -0.374), -26.847 (95% CI -37.562, -16.132), and 0.054 (95% CI 0.015, 0.094) respectively. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients with or without diabetes with regression β of -2.947 (p=0.004), 2.801 (p=0.005), and -3.568 (p≤0.001), respectively. Diabetic patients with dengue had a higher rate of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) than non-diabetic patients. They also had lower blood albumin, were older, and higher triglyceride levels. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients. Dengue patients with diabetes tended to have more severe

  12. Natural vertical transmission of dengue viruses by Aedes aegypti in Bolivia

    Science.gov (United States)

    Le Goff, G.; Revollo, J.; Guerra, M.; Cruz, M.; Barja Simon, Z.; Roca, Y.; Vargas Florès, J.; Hervé, J.P.

    2011-01-01

    The natural transmission of dengue virus from an infected female mosquito to its progeny, namely the vertical transmission, was researched in wild caught Aedes aegypti during an important outbreak in the town of Santa Cruz de la Sierra, Bolivia. Mosquitoes were collected at the preimaginal stages (eggs, larvae and pupae) then reared up to adult stage for viral detection using molecular methods. Dengue virus serotypes 1 and 3 were found to be co-circulating with significant higher prevalence in male than in female mosquitoes. Of the 97 pools of Ae. aegypti (n = 635 male and 748 female specimens) screened, 14 pools, collected in February-May in 2007, were found positive for dengue virus infection: five DEN-1 and nine DEN-3. The average true infection rate (TIR) and minimum infection rate (MIR) were respectively 1.08% and 1.01%. These observations suggest that vertical transmission of dengue virus may be detected in vectors at the peak of an outbreak as well as several months before an epidemic occurs in human population. PMID:21894270

  13. Acute Systemic Infection with Dengue Virus Leads to Vascular Leakage and Death through Tumor Necrosis Factor-α and Tie2/Angiopoietin Signaling in Mice Lacking Type I and II Interferon Receptors.

    Science.gov (United States)

    Phanthanawiboon, Supranee; Limkittikul, Kriengsak; Sakai, Yusuke; Takakura, Nobuyuki; Saijo, Masayuki; Kurosu, Takeshi

    2016-01-01

    Severe dengue is caused by host responses to viral infection, but the pathogenesis remains unknown. This is, in part, due to the lack of suitable animal models. Here, we report a non-mouse-adapted low-passage DENV-3 clinical isolate, DV3P12/08, derived from recently infected patients. DV3P12/08 caused a lethal systemic infection in type I and II IFN receptor KO mice (IFN-α/β/γR KO mice), which have the C57/BL6 background. Infection with DV3P12/08 induced a cytokine storm, resulting in severe vascular leakage (mainly in the liver, kidney and intestine) and organ damage, leading to extensive hemorrhage and rapid death. DV3P12/08 infection triggered the release of large amounts of TNF-α, IL-6, and MCP-1. Treatment with a neutralizing anti-TNF-α antibody (Ab) extended survival and reduced liver damage without affecting virus production. Anti-IL-6 neutralizing Ab partly prolonged mouse survival. The anti-TNF-α Ab suppressed IL-6, MCP-1, and IFN-γ levels, suggesting that the severe response to infection was triggered by TNF-α. High levels of TNF-α mRNA were expressed in the liver and kidneys, but not in the small intestine, of infected mice. Conversely, high levels of IL-6 mRNA were expressed in the intestine. Importantly, treatment with Angiopoietin-1, which is known to stabilize blood vessels, prolonged the survival of DV3P12/08-infected mice. Taken together, the results suggest that an increased level of TNF-α together with concomitant upregulation of Tie2/Angiopoietin signaling have critical roles in severe dengue infection.

  14. Mathematical modeling on T-cell mediated adaptive immunity in primary dengue infections.

    Science.gov (United States)

    Sasmal, Sourav Kumar; Dong, Yueping; Takeuchi, Yasuhiro

    2017-09-21

    At present, dengue is the most common mosquito-borne viral disease in the world, and the global dengue incidence is increasing day by day due to climate changing. Here, we present a mathematical model of dengue viruses (DENVs) dynamics in micro-environment (cellular level) consisting of healthy cells, infected cells, virus particles and T-cell mediated adaptive immunity. We have considered the explicit role of cytokines and antibody in our model. We find that the virus load goes down to zero within 6 days as it is common for DENV infection. From our analysis, we have identified the important model parameters and done the numerical simulation with respect to such important parameters. We have shown that the cytokine mediated virus clearance plays a very important role in dengue dynamics. It can change the dynamical behavior of the system and causes essential extinction of the virus. Finally, we have incorporated the antiviral treatment for dengue in our model and shown that the basic reproduction number is directly proportional to the antiviral treatment effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. STRUKTUR PROTEOMIK VIRUS DENGUE DAN MANFAATNYA SEBAGAI TARGET ANTIVIRUS

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    Novia Rachmayanti

    2014-09-01

    Full Text Available AbstrakVirus dengue (DENV telah menyebabkan sekitar 50 juta kasus infeksi demam berdarah setiap tahunnya, akan tetapi hingga saat ini belum terdapat vaksin maupun antivirus yang mampu mencegah atau mengobati penyakit tersebut. Selama pengembangan vaksin dan antivirus, diperoleh berbagai informasi tentang struktur protein DENV yang dapat dimanfaatkan sebagai target obat. Makalah membahas tentang struktur proteomik pada DENV, yaitu glikoprotein pada envelope, NS3 protease, NS3 helikase, NS5 metiltransferase, dan NS5 RNA-dependent RNA polimerase.AbstractDengue virus (DENV has caused over 50 millions infection every year. However, to date neither vaccine nor medicine could be used to prevent or cure the illness. During researches in finding the vaccine or antiviral for DENV, information on DENV protein structure has been obtained which is potentially used as drug target. This paper disscuss DENV proteomic structure that consist of envelope glicoprotein, NS3 protease, NS3 helicase, NS5 methyl-transferase, and NS5 RNA-dependent RNA polymerase.

  16. Effect of Wolbachia on Dengue infection in Endemic districts of Odisha

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    Ipsita Mohanty

    2017-10-01

    Full Text Available Dengue is the most important arboviral disease posing considerable threat to human and animal health in tropical and subtropical countries. The causative agent for dengue viruses (DENV are primarily the infectious female Aedes aegypti mosquitoes and to a lesser extent its sister taxon infectious female Aedes albopictus mosquitoes. Persistent DENV infections play a role in the cycling pattern of dengue outbreaks. Due to lack of proper treatment, strategies for blocking pathogen transmission by mosquito vectors have been proposed as a means of augmenting current control measures to reduce the growing burden of vector-borne diseases. In this scenario, the use of Wolbachia has been proposed to reduce dengue transmission. Wolbachia, a gram negative endosymbiont bacterium is naturally present in over 20% of all insects including Aedes albopictus mosquito. In our study, polymerase chain reaction (PCR was used to determine the presence of Wolbachia from field collected Ae. albopictus from various parts of the Odisha using wsp primers. Ae. albopictus had Wolbachia infection ranging from 65 to 100%. Field collected Wolbachia infected mosquitoes were challenged with DENV infection. At seven days following infected blood-feeding, an increase in Wolbachia densities was displayed to a greater extent compared to control mosquitoes. Our result indicates that virus-blocking is likely to persist in Wolbachia-infected mosquitoes suggesting that Wolbachia may serve as a successful biocontrol strategy for reducing dengue transmission in the field.

  17. Phospholipase A2 isolated from the venom of Crotalus durissus terrificus inactivates dengue virus and other enveloped viruses by disrupting the viral envelope.

    Directory of Open Access Journals (Sweden)

    Vanessa Danielle Muller

    Full Text Available The Flaviviridae family includes several virus pathogens associated with human diseases worldwide. Within this family, Dengue virus is the most serious threat to public health, especially in tropical and sub-tropical regions of the world. Currently, there are no vaccines or specific antiviral drugs against Dengue virus or against most of the viruses of this family. Therefore, the development of vaccines and the discovery of therapeutic compounds against the medically most important flaviviruses remain a global public health priority. We previously showed that phospholipase A2 isolated from the venom of Crotalus durissus terrificus was able to inhibit Dengue virus and Yellow fever virus infection in Vero cells. Here, we present evidence that phospholipase A2 has a direct effect on Dengue virus particles, inducing a partial exposure of genomic RNA, which strongly suggests inhibition via the cleavage of glycerophospholipids at the virus lipid bilayer envelope. This cleavage might induce a disruption of the lipid bilayer that causes a destabilization of the E proteins on the virus surface, resulting in inactivation. We show by computational analysis that phospholipase A2 might gain access to the Dengue virus lipid bilayer through the pores found on each of the twenty 3-fold vertices of the E protein shell on the virus surface. In addition, phospholipase A2 is able to inactivate other enveloped viruses, highlighting its potential as a natural product lead for developing broad-spectrum antiviral drugs.

  18. Hirsutine, an Indole Alkaloid of Uncaria rhynchophylla, Inhibits Late Step in Dengue Virus Lifecycle

    OpenAIRE

    Hishiki, Takayuki; Kato, Fumihiro; Tajima, Shigeru; Toume, Kazufumi; Umezaki, Masahito; Takasaki, Tomohiko; Miura, Tomoyuki

    2017-01-01

    Dengue virus (DENV) is transmitted to humans by Aedes mosquitoes and is a public health issue worldwide. No antiviral drugs specific for treating dengue infection are currently available. To identify novel DENV inhibitors, we analyzed a library of 95 compounds and 120 extracts derived from crude drugs (herbal medicines). In the primary screening, A549 cells infected with DENV-1 were cultured in the presence of each compound and extract at a final concentration of 10 μM (compound) and 100 μg/m...

  19. Optimization of a method for the detection of immunopotentiating antibodies against serotype 1 of dengue virus

    International Nuclear Information System (INIS)

    Soto Garita, Claudio

    2014-01-01

    An immunopotentiation trial has used sera from dengue seropositive patients from Costa Rica's endemic areas. The detection and semi-quantification of immunopotentiating antibodies were optimized against dengue virus serotype 1. The cell line K562 (human erythromyeloblastoid leukemia cells) has been more efficient than the U937 (human histiocytic lymphoma cells). A more adequate detection of immunopotentiating antibodies was determined. The optimal infection and virus-antibody incubation parameters are demonstrated for the detection of immunopotentiating antibodies with the immunostaining technique. The immuno-optimized assay has allowed the detection and semi-quantification of immunopotentiating antibodies against serotype 1 of dengue virus. Samples of strong positive, weak positive and dengue negative sera are analyzed. The end has been to evaluate the usefulness in the detection and semi-quantification of immunopotentiating antibodies. The presence of immunopotentiating antibodies was demonstrated against dengue virus serotype 1 in endemic zones of Costa Rica, to complement with the evaluation of the other existing serotypes is recommended [es

  20. Deranged liver among Sudanese patients with dengue virus ...

    African Journals Online (AJOL)

    Background: Deranged liver is a well-recognized feature of dengue infection, often demonstrated by coagulopathy and mild to moderate increase in transaminase levels although jaundice and fulminant hepatic failure are generally uncommon. Objective: This study aimed to evaluate the hepatic effect of dengue fever ...

  1. First record of natural vertical transmission of dengue virus in Aedes aegypti from Cuba.

    Science.gov (United States)

    Gutiérrez-Bugallo, Gladys; Rodriguez-Roche, Rosmari; Díaz, Gisell; Vázquez, Antonio A; Alvarez, Mayling; Rodríguez, Magdalena; Bisset, Juan A; Guzman, Maria G

    2017-10-01

    While horizontal transmission (human-mosquito-human) of dengue viruses largely determines the epidemiology of the disease, vertical transmission (infected female mosquito- infected offspring) has been suggested as a mechanism that ensures maintenance of the virus during adverse conditions for horizontal transmission to occur. The purpose of this study was to analyze the natural infection of larval stages of Aedes aegypti (Diptera: Culicidae) with the dengue virus (DENV) in Cuba. Here, we report vertical transmission of DENV-3 genotype III in natural populations of Ae. aegypti through RT-PCR detection and serotyping plus sequencing. Our report constitutes the first record of vertical transmission of DENV in Ae. aegypti from Cuba with details of its serotype and genotype. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Synchrony of sylvatic dengue isolations: a multi-host, multi-vector SIR model of dengue virus transmission in Senegal.

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    Benjamin M Althouse

    Full Text Available Isolations of sylvatic dengue-2 virus from mosquitoes, humans and non-human primates in Senegal show synchronized multi-annual dynamics over the past 50 years. Host demography has been shown to directly affect the period between epidemics in other pathogen systems, therefore, one might expect unsynchronized multi-annual cycles occurring in hosts with dramatically different birth rates and life spans. However, in Senegal, we observe a single synchronized eight-year cycle across all vector species, suggesting synchronized dynamics in all vertebrate hosts. In the current study, we aim to explore two specific hypotheses: 1 primates with different demographics will experience outbreaks of dengue at different periodicities when observed as isolated systems, and that coupling of these subsystems through mosquito biting will act to synchronize incidence; and 2 the eight-year periodicity of isolations observed across multiple primate species is the result of long-term cycling in population immunity in the host populations. To test these hypotheses, we develop a multi-host, multi-vector Susceptible, Infected, Removed (SIR model to explore the effects of coupling multiple host-vector systems of dengue virus transmission through cross-species biting rates. We find that under small amounts of coupling, incidence in the host species synchronize. Long-period multi-annual dynamics are observed only when prevalence in troughs reaches vanishingly small levels (< 10(-10, suggesting that these dynamics are inconsistent with sustained transmission in this setting, but are consistent with local dengue virus extinctions followed by reintroductions. Inclusion of a constant introduction of infectious individuals into the system causes the multi-annual periods to shrink, while the effects of coupling remain the same. Inclusion of a stochastic rate of introduction allows for multi-annual periods at a cost of reduced synchrony. Thus, we conclude that the eight-year period

  3. Antiviral activity of four types of bioflavonoid against dengue virus type-2

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    Zandi Keivan

    2011-12-01

    Full Text Available Abstract Background Dengue is a major mosquito-borne disease currently with no effective antiviral or vaccine available. Effort to find antivirals for it has focused on bioflavonoids, a plant-derived polyphenolic compounds with many potential health benefits. In the present study, antiviral activity of four types of bioflavonoid against dengue virus type -2 (DENV-2 in Vero cell was evaluated. Anti-dengue activity of these compounds was determined at different stages of DENV-2 infection and replication cycle. DENV replication was measured by Foci Forming Unit Reduction Assay (FFURA and quantitative RT-PCR. Selectivity Index value (SI was determined as the ratio of cytotoxic concentration 50 (CC50 to inhibitory concentration 50 (IC50 for each compound. Results The half maximal inhibitory concentration (IC50 of quercetin against dengue virus was 35.7 μg mL-1 when it was used after virus adsorption to the cells. The IC50 decreased to 28.9 μg mL-1 when the cells were treated continuously for 5 h before virus infection and up to 4 days post-infection. The SI values for quercetin were 7.07 and 8.74 μg mL-1, respectively, the highest compared to all bioflavonoids studied. Naringin only exhibited anti-adsorption effects against DENV-2 with IC50 = 168.2 μg mL-1 and its related SI was 1.3. Daidzein showed a weak anti-dengue activity with IC50 = 142.6 μg mL-1 when the DENV-2 infected cells were treated after virus adsorption. The SI value for this compound was 1.03. Hesperetin did not exhibit any antiviral activity against DENV-2. The findings obtained from Foci Forming Unit Reduction Assay (FFURA were corroborated by findings of the qRT-PCR assays. Quercetin and daidzein (50 μg mL-1 reduced DENV-2 RNA levels by 67% and 25%, respectively. There was no significant inhibition of DENV-2 RNA levels with naringin and hesperetin. Conclusion Results from the study suggest that only quercetin demonstrated significant anti-DENV-2 inhibitory activities. Other

  4. Zika virus infection acquired during brief travel to Indonesia.

    Science.gov (United States)

    Kwong, Jason C; Druce, Julian D; Leder, Karin

    2013-09-01

    Zika virus infection closely resembles dengue fever. It is possible that many cases are misdiagnosed or missed. We report a case of Zika virus infection in an Australian traveler who returned from Indonesia with fever and rash. Further case identification is required to determine the evolving epidemiology of this disease.

  5. Phylogenetic and evolutionary analyses of dengue viruses isolated in Jakarta, Indonesia.

    Science.gov (United States)

    Lestari, C S Whinie; Yohan, Benediktus; Yunita, Anisa; Meutiawati, Febrina; Hayati, Rahma Fitri; Trimarsanto, Hidayat; Sasmono, R Tedjo

    2017-12-01

    Dengue has affected Indonesia for the last five decades and become a major health problem in many cities in the country. Jakarta, the capital of Indonesia, reports dengue cases annually, with several outbreaks documented. To gain information on the dynamic and evolutionary history of dengue virus (DENV) in Jakarta, we conducted phylogenetic and evolutionary analyses of DENV isolated in 2009. Three hundred thirty-three dengue-suspected patients were recruited. Our data revealed that dengue predominantly affected young adults, and the majority of cases were due to secondary infection. A total of 171 virus isolates were successfully serotyped. All four DENV serotypes were circulating in the city, and DENV-1 was the predominant serotype. The DENV genotyping of 17 isolates revealed the presence of Genotypes I and IV in DENV-1, while DENV-2 isolates were grouped into the Cosmopolitan genotype. The grouping of isolates into Genotype I and II was seen for DENV-3 and DENV-4, respectively. Evolutionary analysis revealed the relatedness of Jakarta isolates with other isolates from other cities in Indonesia and isolates from imported cases in other countries. We revealed the endemicity of DENV and the role of Jakarta as the potential source of imported dengue cases in other countries. Our study provides genetic information regarding DENV from Jakarta, which will be useful for upstream applications, such as the study of DENV epidemiology and evolution and transmission dynamics.

  6. Nordihydroguaiaretic acid (NDGA) inhibits replication and viral morphogenesis of dengue virus.

    Science.gov (United States)

    Soto-Acosta, Rubén; Bautista-Carbajal, Patricia; Syed, Gulam H; Siddiqui, Aleem; Del Angel, Rosa M

    2014-09-01

    Dengue is the most common mosquito borne viral disease in humans. The infection with any of the 4 dengue virus serotypes (DENV) can either be asymptomatic or manifest in two clinical forms, the mild dengue fever or the more severe dengue hemorrhagic fever that may progress into dengue shock syndrome. A DENV replicative cycle relies on host lipid metabolism; specifically, DENV infection modulates cholesterol and fatty acid synthesis, generating a lipid-enriched cellular environment necessary for viral replication. Thus, the aim of this work was to evaluate the anti-DENV effect of the Nordihydroguaiaretic acid (NDGA), a hypolipidemic agent with antioxidant and anti-inflammatory properties. A dose-dependent inhibition in viral yield and NS1 secretion was observed in supernatants of infected cells treated for 24 and 48 h with different concentrations of NDGA. To evaluate the effect of NDGA in DENV replication, a DENV4 replicon transfected Vero cells were treated with different concentrations of NDGA. NDGA treatment significantly reduced DENV replication, reiterating the importance of lipids in viral replication. NDGA treatment also led to reduction in number of lipid droplets (LDs), the neutral lipid storage organelles involved in DENV morphogenesis that are known to increase in number during DENV infection. Furthermore, NDGA treatment resulted in dissociation of the C protein from LDs. Overall our results suggest that NDGA inhibits DENV infection by targeting genome replication and viral assembly. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Evaluation of concurrent malaria and dengue infections among febrile patients

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    Parul D Shah

    2017-01-01

    Full Text Available Context: Despite a wide overlap between endemic areas for two important vector-borne infections, malaria and dengue, published reports of co-infections are scarce till date. Aims: To find the incidence of dengue and malaria co-infection as well as to ascertain the severity of such dengue and malaria co-infection based on clinical and haematological parameters. Setting and Design: Observational, retrospective cross-sectional study was designed including patients who consulted the tertiary care hospital of Ahmedabad seeking treatment for fever compatible with malaria and/or dengue. Subjects and Methods: A total of 8364 serum samples from clinically suspected cases of fever compatible with malaria and/or dengue were collected. All samples were tested for dengue NS-1 antigen before 5 days of onset of illness and for dengue IgM after 5 days of onset of illness. In all samples, malaria diagnosis was based on the identification of Plasmodium parasites on a thin and thick blood films microscopy. Results: Only 10.27% (859 patients with fever were tested positive for dengue and 5.1% (434 were tested positive for malaria. 3.14% (27 dengue cases show concurrent infection with malarial parasites. Hepatomegaly and jaundice 37.03% (10, haemorrhagic manifestations 18.51% (5 and kidney failure 3.7% (1, haemoglobin <12 g/dl 100% (27 and thrombocytopenia (platelet count <150,000/cmm 96.29% (26 were common in malaria and dengue co-infections and were much more common in Plasmodium falciparum infections. Conclusion: All febrile patients must be tested for malaria and dengue, both otherwise one of them will be missed in case of concurrent infections which could lead to severe diseases with complications.

  8. An evaluation of asymptomatic Dengue infections among blood donors during the 2014 Dengue outbreak in Guangzhou, China.

    Science.gov (United States)

    Liao, Qiao; Shan, Zhengang; Wang, Min; Huang, Jieting; Xu, Ru; Huang, Ke; Tang, Xi; Zhang, Weiyun; Nelson, Kenrad; Li, Chengyao; Fu, Yongshui; Rong, Xia

    2017-11-01

    In 2014, an outbreak of dengue virus (DENV) infection led to 45 171 clinical cases diagnosed in Guangdong province, Southern China. However, the potential risk of blood donors asymptomatically infected with DENV has not been evaluated . In the current study we detected anti-DENV IgG antibody and RNA in volunteer Chinese blood donors. We found that anti-DENV IgG antibody was positively detected in 3.4% (51/1500) and two donors were detected as being DENV RNA positive out of 3000 blood samples. We concluded that the presence of potential DENV in blood donors might be potential risk for blood safety. Therefore, screening for DENV infection should be considered in blood donations during a period of dengue outbreak in high epidemic area of China. © 2017 Wiley Periodicals, Inc.

  9. Performance of commercial dengue NS1 ELISA and molecular analysis of NS1 gene of dengue viruses obtained during surveillance in Indonesia.

    Science.gov (United States)

    Aryati, Aryati; Trimarsanto, Hidayat; Yohan, Benediktus; Wardhani, Puspa; Fahri, Sukmal; Sasmono, R Tedjo

    2013-12-29

    Early diagnosis of dengue infection is crucial for better management of the disease. Diagnostic tests based on the detection of dengue virus (DENV) Non Structural Protein 1 (NS1) antigen are commercially available with different sensitivities and specificities observed in various settings. Dengue is endemic in Indonesia and clinicians are increasingly using the NS1 detection for dengue confirmation. This study described the performance of Panbio Dengue Early NS1 and IgM Capture ELISA assays for dengue detection during our surveillance in eight cities in Indonesia as well as the genetic diversity of DENV NS1 genes and its relationship with the NS1 detection. The NS1 and IgM/IgG ELISA assays were used for screening and confirmation of dengue infection during surveillance in 2010-2012. Collected serum samples (n = 440) were subjected to RT-PCR and virus isolation, in which 188 samples were confirmed for dengue infection. The positivity of the ELISA assays were correlated with the RT-PCR results to obtain the sensitivity of the assays. The NS1 genes of 48 Indonesian virus isolates were sequenced and their genetic characteristics were studied. Using molecular data as gold standard, the sensitivity of NS1 ELISA assay for samples from Indonesia was 56.4% while IgM ELISA was 73.7%. When both NS1 and IgM results were combined, the sensitivity increased to 89.4%. The NS1 sensitivity varied when correlated with city/geographical origins and DENV serotype, in which the lowest sensitivity was observed for DENV-4 (19.0%). NS1 sensitivity was higher in primary (67.6%) compared to secondary infection (48.2%). The specificity of NS1 assay for non-dengue samples were 100%. The NS1 gene sequence analysis of 48 isolates revealed the presence of polymorphisms of the NS1 genes which apparently did not influence the NS1 sensitivity. We observed a relatively low sensitivity of NS1 ELISA for dengue detection on RT-PCR-positive dengue samples. The detection rate increased significantly

  10. Circulating serotypes of dengue virus and their incursion into non-endemic areas of Pakistan; a serious threat.

    Science.gov (United States)

    Ali, Amjad; Ahmad, Habib; Idrees, Muhammad; Zahir, Fazli; Ali, Ijaz

    2016-08-26

    Dengue virus is circulating in Pakistan since 1994, which causes major and minor outbreaks in many areas of the country. The incidence of dengue in Pakistan in past years mainly restricted to parts of Sindh and Punjab provinces. As such, a severe dengue outbreak appeared in Pakistan in 2011, particularly in Punjab province with Lahore as the most hit city (290 deaths). In 2013, for the first time in the history of Pakistan, dengue outbreak erupted in Swat District, Khyber Pakhtunkhwa, which claimed more than 57 lives. Hence this study was conducted to document circulating serotypes of dengue virus in Pakistan in 2011 and 2013 dengue outbreaks in two different territories/areas of the country. In total, 1340 blood samples from people having dengue (ELISA positive) and/or dengue like symptoms from various cities/areas of Punjab and Swat, Khyber Pakhtunkhwa (KP) were collected and analyzed by reverse transcription polymerase chain reaction (RT-PCR) using serotype specific primers. The results indicated that all the four dengue virus serotypes were circulating in Punjab Province with highest frequency of DENV-2 (41.64 %) and DENV-3 (41.05 %). Similarly, DENV-2 (41.66 %) and DENV-3 (35.0 %) were dominant serotypes detected in KP-based people lived in Punjab. On the other hand only DENV-2 (40.0 %) and DENV-3 (60.0 %) were detected in Swat District. Furthermore an important observation noted in this study was mixed infection of DENV-2 and DENV-3 in Punjab in 2011 (3.81 %) and in people from KP infected in Punjab (8.33 %) which may account for the high mortality and morbidity rates as compared to previous outbreaks. Over all male population was mostly infected as compared to females and people in the age group between 15 to 45 was the highest infected group. The findings of this study indicate that all four serotypes of dengue virus are circulating in Punjab whereas serotypes 2 and 3 introduced for the first time into Swat, KP in 2013; about 600 km away from Lahore

  11. Fine Scale Spatiotemporal Clustering of Dengue Virus Transmission in Children and Aedes aegypti in Rural Thai Villages

    NARCIS (Netherlands)

    Yoon, I.K.; Getis, A.; Aldstadt, J.; Rothman, A.L.; Tannitisupawong, D.; Koenraadt, C.J.M.; Fansiri, T.; Jones, J.W.; Morrison, A.C.; Jarman, R.G.; Nisalak, A.; Mammen Jr., M.P.; Thammapalo, S.; Srikiatkhachorn, A.; Green, S.; Libraty, D.H.; Gibbons, R.V.; Endy, T.; Pimgate, C.; Scott, T.W.

    2012-01-01

    Background Based on spatiotemporal clustering of human dengue virus (DENV) infections, transmission is thought to occur at fine spatiotemporal scales by horizontal transfer of virus between humans and mosquito vectors. To define the dimensions of local transmission and quantify the factors that

  12. Evidence of dengue virus transmission and factors associated with the presence of anti-dengue virus antibodies in humans in three major towns in Cameroon.

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    Maurice Demanou

    2014-07-01

    Full Text Available Dengue is not well documented in Africa. In Cameroon, data are scarce, but dengue infection has been confirmed in humans. We conducted a study to document risk factors associated with anti-dengue virus Immunoglobulin G seropositivity in humans in three major towns in Cameroon.A cross sectional survey was conducted in Douala, Garoua and Yaounde, using a random cluster sampling design. Participants underwent a standardized interview and were blood sampled. Environmental and housing characteristics were recorded. Randomized houses were prospected to record all water containers, and immature stages of Aedes mosquitoes were collected. Sera were screened for anti-dengue virus IgG and IgM antibodies. Risk factors of seropositivity were tested using logistic regression methods with random effects. Anti-dengue IgG were found from 61.4% of sera in Douala (n = 699, 24.2% in Garoua (n = 728 and 9.8% in Yaounde (n = 603. IgM were found from 0.3% of Douala samples, 0.1% of Garoua samples and 0.0% of Yaounde samples. Seroneutralization on randomly selected IgG positive sera showed that 72% (n = 100 in Douala, 80% (n = 94 in Garoua and 77% (n = 66 in Yaounde had antibodies specific for dengue virus serotype 2 (DENV-2. Age, temporary house walls materials, having water-storage containers, old tires or toilets in the yard, having no TV, having no air conditioning and having travelled at least once outside the city were independently associated with anti-dengue IgG positivity in Douala. Age, having uncovered water containers, having no TV, not being born in Garoua and not breeding pigs were significant risk factors in Garoua. Recent history of malaria, having banana trees and stagnant water in the yard were independent risk factors in Yaounde.In this survey, most identified risk factors of dengue were related to housing conditions. Poverty and underdevelopment are central to the dengue epidemiology in Cameroon.

  13. Evidence for the Inhibition of Dengue Virus Binding in the Presence of Silver Nanoparticles

    Science.gov (United States)

    2015-03-26

    with DENV are known to increase in severity from Dengue Fever to Dengue Hemorrhagic Fever or Dengue Shock Syndrome. Currently, no vaccines or...DENV is a member of the Flavivirus family, as is the yellow fever virus (the family’s prototype), West Nile, Japanese encephalitis virus, and many...perspective/2013/10/ researchers - identify-fifth-dengue-subtype. [20] C. Moore, “UTMB Galveston Researchers Discover First New Dengue Fever Serotype In 50

  14. Complexity of Human Antibody Response to Dengue Virus: Implication for Vaccine Development

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    Wen-Yang Tsai

    2017-07-01

    Full Text Available The four serotypes of dengue virus (DENV are the leading cause of arboviral diseases in humans. Decades of efforts have made remarkable progress in dengue vaccine development. Despite the first dengue vaccine (dengvaxia from Sanofi Pasteur, a live-attenuated tetravalent chimeric yellow fever-dengue vaccine, has been licensed by several countries since 2016, its overall moderate efficacy (56.5–60.8% in the presence of neutralizing antibodies during the Phase 2b and 3 trials, lower efficacy among dengue naïve compared with dengue experienced individuals, and increased risk of hospitalization among young children during the follow-up highlight the need for a better understanding of humoral responses after natural DENV infection. Recent studies of more than 300 human monoclonal antibodies (mAbs against DENV have led to the discovery of several novel epitopes on the envelope protein recognized by potent neutralizing mAbs. This information together with in-depth studies on polyclonal sera and B-cells following natural DENV infection has tremendous implications for better immunogen design for a safe and effective dengue vaccine. This review outlines the progress in our understanding of mouse mAbs, human mAbs, and polyclonal sera against DENV envelope and precursor membrane proteins, two surface proteins involved in vaccine development, following natural infection; analyses of these discoveries have provided valuable insight into new strategies involving molecular technology to induce more potent neutralizing antibodies and less enhancing antibodies for next-generation dengue vaccine development.

  15. Dengue in Bali: Clinical characteristics and genetic diversity of circulating dengue viruses.

    Science.gov (United States)

    Megawati, Dewi; Masyeni, Sri; Yohan, Benediktus; Lestarini, Asri; Hayati, Rahma F; Meutiawati, Febrina; Suryana, Ketut; Widarsa, Tangking; Budiyasa, Dewa G; Budiyasa, Ngurah; Myint, Khin S A; Sasmono, R Tedjo

    2017-05-01

    A high number of dengue cases are reported annually in Bali. Despite the endemicity, limited data on dengue is available for Bali localities. Molecular surveillance study was conducted to explore the clinical and virological characteristics of dengue patients in urban Denpasar and rural Gianyar areas in Bali during the peak season in 2015. A total of 205 adult dengue-suspected patients were recruited in a prospective cross-sectional study. Demographic and clinical information were obtained, and dengue screening was performed using NS1 and IgM/IgG ELISAs. Viral RNA was subsequently extracted from patients' sera for serotyping using conventional RT-PCR and Simplexa Dengue real-time RT-PCR, followed by genotyping with sequencing method. We confirmed 161 patients as having dengue by NS1 and RT-PCR. Among 154 samples successfully serotyped, the DENV-3 was predominant, followed by DENV-1, DENV-2, and DENV-4. Serotype predominance was different between Denpasar and Gianyar. Genotyping results classify DENV-1 isolates into Genotype I and DENV-2 as Cosmopolitan Genotype. The classification grouped isolates into Genotype I and II for DENV-3 and DENV-4, respectively. Clinical parameters showed no relationship between infecting serotypes and severity. We observed the genetic diversity of circulating DENV isolates and their relatedness with historical data and importation to other countries. Our data highlights the role of this tourist destination as a potential source of dengue transmission in the region.

  16. A community-based prospective cohort study of dengue viral infection in Malaysia: the study protocol.

    Science.gov (United States)

    Jahan, Nowrozy Kamar; Ahmad, Mohtar Pungut; Dhanoa, Amreeta; Meng, Cheong Yuet; Ming, Lau Wee; Reidpath, Daniel D; Allotey, Pascale; Zaini, Anuar; Phipps, Maude Elvira; Fatt, Quek Kia; Rabu, Aman Bin; Sirajudeen, Rowther; Fatan, Ahmad AbdulBasitz Ahmad; Ghafar, Faidzal Adlee; Ahmad, Hamdan Bin; Othman, Iekhsan; SyedHassan, Sharifah

    2016-08-11

    Globally, dengue infections constitute a significant public health burden. In recent decades, Malaysia has become a dengue hyper-endemic country with the co-circulation of the four dengue virus serotypes. The cyclical dominance of sub-types contributes to a pattern of major outbreaks. The consequences can be observed in the rising incidence of reported dengue cases and dengue related deaths. Understanding the complex interaction of the dengue virus, its human hosts and the mosquito vectors at the community level may help develop strategies for addressing the problem. A prospective cohort study will be conducted in Segamat district of Johor State in Peninsular Malaysia. Researchers received approval from the Malaysian Medical Research Ethics Committee and Monash University Human Research Ethics Committee. The study will be conducted at a Malaysian based health and demographic surveillance site over a 1 year period in three different settings (urban, semi-urban and rural). The study will recruit healthy adults (male and female) aged 18 years and over, from three ethnic groups (Malay, Chinese and Indian). The sample size calculated using the Fleiss method with continuity correction is 333. Sero-surveillance of participants will be undertaken to identify asymptomatic, otherwise healthy cases; cases with dengue fever who are managed as out-patients; and cases with dengue fever admitted to a hospital. A genetic analysis of the participants will be undertaken to determine whether there is a relationship between genetic predisposition and disease severity. A detailed medical history, past history of dengue infection, vaccination history against other flaviviruses such as Japanese encephalitis and Yellow fever, and the family history of dengue infection will also be collected. In addition, a mosquito surveillance will be carried out simultaneously in recruitment areas to determine the molecular taxonomy of circulating vectors. The research findings will estimate the burden

  17. Dengue retinochoroiditis.

    Science.gov (United States)

    Tabbara, Khalid

    2012-01-01

    Dengue is a mosquito-borne infection caused by a flavivirus. I describe the ocular findings observed in two patients infected with dengue virus who presented with acute onset of loss of vision preceded by febrile illness, malaise, generalized fatigue headache, and maculopapular rash. Ophthalmologic evaluation in each patient revealed a normal anterior segment. Vitreous cells were noted in one patient. Ophthalmoscopy revealed multiple foci of retinochoroiditis, vasculitis, cotton-wool spots, and retinal hemorrhages. The healing of the lesion showed discrete atrophic and pigmented retinochoroiditic scars. Fluorescein angiography displayed early hypofluorescence and late hyperfluorescence suggestive of leakage. The healed scars showed late staining. The serologic testing showed elevated IgG antibodies, and one had high IgM antibodies to dengue virus. Ocular findings of dengue fever consist of multifocal areas of retinochoroiditis and may lead to loss of vision. In Saudi Arabia, dengue fever should be considered in the differential diagnosis of multifocal chorioretinal lesions and retinal vasculitis.

  18. A Physical Interaction Network of Dengue Virus and Human Proteins*

    Science.gov (United States)

    Khadka, Sudip; Vangeloff, Abbey D.; Zhang, Chaoying; Siddavatam, Prasad; Heaton, Nicholas S.; Wang, Ling; Sengupta, Ranjan; Sahasrabudhe, Sudhir; Randall, Glenn; Gribskov, Michael; Kuhn, Richard J.; Perera, Rushika; LaCount, Douglas J.

    2011-01-01

    Dengue virus (DENV), an emerging mosquito-transmitted pathogen capable of causing severe disease in humans, interacts with host cell factors to create a more favorable environment for replication. However, few interactions between DENV and human proteins have been reported to date. To identify DENV-human protein interactions, we used high-throughput yeast two-hybrid assays to screen the 10 DENV proteins against a human liver activation domain library. From 45 DNA-binding domain clones containing either full-length viral genes or partially overlapping gene fragments, we identified 139 interactions between DENV and human proteins, the vast majority of which are novel. These interactions involved 105 human proteins, including six previously implicated in DENV infection and 45 linked to the replication of other viruses. Human proteins with functions related to the complement and coagulation cascade, the centrosome, and the cytoskeleton were enriched among the DENV interaction partners. To determine if the cellular proteins were required for DENV infection, we used small interfering RNAs to inhibit their expression. Six of 12 proteins targeted (CALR, DDX3X, ERC1, GOLGA2, TRIP11, and UBE2I) caused a significant decrease in the replication of a DENV replicon. We further showed that calreticulin colocalized with viral dsRNA and with the viral NS3 and NS5 proteins in DENV-infected cells, consistent with a direct role for calreticulin in DENV replication. Human proteins that interacted with DENV had significantly higher average degree and betweenness than expected by chance, which provides additional support for the hypothesis that viruses preferentially target cellular proteins that occupy central position in the human protein interaction network. This study provides a valuable starting point for additional investigations into the roles of human proteins in DENV infection. PMID:21911577

  19. A physical interaction network of dengue virus and human proteins.

    Science.gov (United States)

    Khadka, Sudip; Vangeloff, Abbey D; Zhang, Chaoying; Siddavatam, Prasad; Heaton, Nicholas S; Wang, Ling; Sengupta, Ranjan; Sahasrabudhe, Sudhir; Randall, Glenn; Gribskov, Michael; Kuhn, Richard J; Perera, Rushika; LaCount, Douglas J

    2011-12-01

    Dengue virus (DENV), an emerging mosquito-transmitted pathogen capable of causing severe disease in humans, interacts with host cell factors to create a more favorable environment for replication. However, few interactions between DENV and human proteins have been reported to date. To identify DENV-human protein interactions, we used high-throughput yeast two-hybrid assays to screen the 10 DENV proteins against a human liver activation domain library. From 45 DNA-binding domain clones containing either full-length viral genes or partially overlapping gene fragments, we identified 139 interactions between DENV and human proteins, the vast majority of which are novel. These interactions involved 105 human proteins, including six previously implicated in DENV infection and 45 linked to the replication of other viruses. Human proteins with functions related to the complement and coagulation cascade, the centrosome, and the cytoskeleton were enriched among the DENV interaction partners. To determine if the cellular proteins were required for DENV infection, we used small interfering RNAs to inhibit their expression. Six of 12 proteins targeted (CALR, DDX3X, ERC1, GOLGA2, TRIP11, and UBE2I) caused a significant decrease in the replication of a DENV replicon. We further showed that calreticulin colocalized with viral dsRNA and with the viral NS3 and NS5 proteins in DENV-infected cells, consistent with a direct role for calreticulin in DENV replication. Human proteins that interacted with DENV had significantly higher average degree and betweenness than expected by chance, which provides additional support for the hypothesis that viruses preferentially target cellular proteins that occupy central position in the human protein interaction network. This study provides a valuable starting point for additional investigations into the roles of human proteins in DENV infection.

  20. Re-emergence of dengue virus serotype 2 strains in the 2013 outbreak in Nepal

    Science.gov (United States)

    Gupta, Birendra Prasad; Singh, Sneha; Kurmi, Roshan; Malla, Rajani; Sreekumar, Easwaran; Manandhar, Krishna Das

    2015-01-01

    Background & objectives: Epidemiological interventions and mosquito control are the available measures for dengue control. The former approach uses serotype and genetic information on the circulating virus strains. Dengue has been frequently reported from Nepal, but this information is mostly lacking. The present study was done to generate a comprehensive clinical and virological picture of a dengue outbreak in Nepal during 2013. Methods: A hospital-based study involving patients from five districts of Nepal was carried out. Demographic information, clinical details and dengue serological status were obtained. Viral RNA was characterized at the molecular level by reverse-transcription polymerase chain reaction (RT-PCR), nucleotide sequencing and phylogenetic analysis. Results: From among the 2340 laboratory-confirmed dengue cases during the study period, 198 patients consented for the study. Clinically they had fever (100%), headache (59.1%), rashes (18.2%), retro-orbital pain (30.3%), vomiting (15.1%), joint pain (28.8%) and thrombocytopenia (74.3%). Fifteen (7.5%) of them had mucosal bleeding manifestations, and the rest were uncomplicated dengue fever. The patients were mostly adults with a mean age of 45.75 ± 38.61 yr. Of the 52 acute serum samples tested, 15 were positive in RT-PCR. The causative virus was identified as DENV serotype 2 belonging to the Cosmopolitan genotype. Interpretations & conclusions: We report here the involvement of DENV serotype 2 in an outbreak in Nepal in 2013. Earlier outbreaks in the region in 2010 were attributed to serotype 1 virus. As serotype shifts are frequently associated with secondary infections and severe disease, there is a need for enhancing surveillance especially in the monsoon and post-monsoon periods to prevent large-scale, severe dengue outbreaks in the region. PMID:26905233

  1. Dengue Virus in Bats from Southeastern Mexico

    Science.gov (United States)

    Sotomayor-Bonilla, Jesús; Chaves, Andrea; Rico-Chávez, Oscar; Rostal, Melinda K.; Ojeda-Flores, Rafael; Salas-Rojas, Mónica; Aguilar-Setien, Álvaro; Ibáñez-Bernal, Sergio; Barbachano-Guerrero, Arturo; Gutiérrez-Espeleta, Gustavo; Aguilar-Faisal, J. Leopoldo; Aguirre, A. Alonso; Daszak, Peter; Suzán, Gerardo

    2014-01-01

    To identify the relationship between landscape use and dengue virus (DENV) occurrence in bats, we investigated the presence of DENV from anthropogenically changed and unaltered landscapes in two Biosphere Reserves: Calakmul (Campeche) and Montes Azules (Chiapas) in southern Mexico. Spleen samples of 146 bats, belonging to 16 species, were tested for four DENV serotypes with standard reverse transcriptase polymerase chain reaction (RT-PCR) protocols. Six bats (4.1%) tested positive for DENV-2: four bats in Calakmul (two Glossophaga soricina, one Artibeus jamaicensis, and one A. lituratus) and two bats in Montes Azules (both A. lituratus). No effect of anthropogenic disturbance on the occurrence of DENV was detected; however, all three RT-PCR–positive bat species are considered abundant species in the Neotropics and well-adapted to disturbed habitats. To our knowledge, this study is the first study conducted in southeastern Mexico to identify DENV-2 in bats by a widely accepted RT-PCR protocol. The role that bats play on DENV's ecology remains undetermined. PMID:24752688

  2. Characterization of retrovirus-based reporter viruses pseudotyped with the precursor membrane and envelope glycoproteins of four serotypes of dengue viruses

    International Nuclear Information System (INIS)

    Hu, H.-P.; Hsieh, S.-C.; King, C.-C.; Wang, W.-K.

    2007-01-01

    In this study, we successfully established retrovirus-based reporter viruses pseudotyped with the precursor membrane and envelope (PrM/E) proteins of each of the four serotypes of dengue viruses, which caused the most important arboviral diseases in this century. Co-sedimentation of the dengue E protein and HIV-1 core proteins by sucrose gradient analysis of the pseudotype reporter virus of dengue virus type 2, D2(HIVluc), and detection of HIV-1 core proteins by immunoprecipitation with anti-E monoclonal antibody suggested that dengue viral proteins were incorporated into the pseudotype viral particles. The infectivity in target cells, as assessed by the luciferase activity, can be inhibited by the lysosomotropic agents, suggesting a pH-dependent mechanism of entry. Amino acid substitutions of the leucine at position 107, a critical residue at the fusion loop of E protein, with lysine resulted in severe impairment in infectivity, suggesting that entry of the pseudotype reporter virus is mediated through the fusogenic properties of E protein. With more and more dengue viral sequences available from different outbreaks worldwide, this sensitive and convenient tool has the potential to facilitate molecular characterization of the PrM/E proteins of dengue field isolates

  3. Transmission of dengue virus from deceased donors to solid organ transplant recipients: case report and literature review.

    Science.gov (United States)

    Rosso, Fernando; Pineda, Juan C; Sanz, Ana M; Cedano, Jorge A; Caicedo, Luis A

    Dengue fever is a vector-transmitted viral infection. Non-vectorial forms of transmission can occur through organ transplantation. We reviewed medical records of donors and recipients with suspected dengue in the first post-transplant week. We used serologic and molecular analysis to confirm the infection. Herein, we describe four cases of dengue virus transmission through solid organ transplantation. The recipients had positive serology and RT-PCR. Infection in donors was detected through serology. All cases presented with fever within the first week after transplantation. There were no fatal cases. After these cases, we implemented dengue screening with NS1 antigen detection in donors during dengue outbreaks, and no new cases were detected. In the literature review, additional cases had been published through August 2017. Transmission of Dengue virus can occur through organ donation. In endemic regions, it is important to suspect and screen for dengue in febrile and thrombocytopenic recipients in the postoperative period. Copyright © 2018 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

  4. Small RNA Profiling in Dengue Virus 2-Infected Aedes Mosquito Cells Reveals Viral piRNAs and Novel Host miRNAs

    NARCIS (Netherlands)

    Miesen, P.; Ivens, A.; Buck, A.H.; Rij, R.P. van

    2016-01-01

    In Aedes mosquitoes, infections with arthropod-borne viruses (arboviruses) trigger or modulate the expression of various classes of viral and host-derived small RNAs, including small interfering RNAs (siRNAs), PIWI interacting RNAs (piRNAs), and microRNAs (miRNAs). Viral siRNAs are at the core of

  5. Dengue viruses binding proteins from Aedes aegypti and Aedes polynesiensis salivary glands

    Directory of Open Access Journals (Sweden)

    Cao-Lormeau Van-Mai

    2009-03-01

    Full Text Available Abstract Dengue virus (DENV, the etiological agent of dengue fever, is transmitted to the human host during blood uptake by an infective mosquito. Infection of vector salivary glands and further injection of infectious saliva into the human host are key events of the DENV transmission cycle. However, the molecular mechanisms of DENV entry into the mosquito salivary glands have not been clearly identified. Otherwise, although it was demonstrated for other vector-transmitted pathogens that insect salivary components may interact with host immune agents and impact the establishment of infection, the role of mosquito saliva on DENV infection in human has been only poorly documented. To identify salivary gland molecules which might interact with DENV at these key steps of transmission cycle, we investigated the presence of proteins able to bind DENV in salivary gland extracts (SGE from two mosquito species. Using virus overlay protein binding assay, we detected several proteins able to bind DENV in SGE from Aedes aegypti (L. and Aedes polynesiensis (Marks. The present findings pave the way for the identification of proteins mediating DENV attachment or entry into mosquito salivary glands, and of saliva-secreted proteins those might be bound to the virus at the earliest step of human infection. The present findings might contribute to the identification of new targets for anti-dengue strategies.

  6. VERTICAL TRANSMISSION OF DENGUE INFECTION: THE FIRST PUTATIVE CASE REPORTED IN CHINA

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    Xueru YIN

    Full Text Available SUMMARY Dengue is a systemic viral infection that is commonly transmitted between humans via mosquitoes. Other modes of transmission such as the vertical one are rare and have been infrequently reported in the literature. This report investigates one case of vertical transmission of dengue in Guangzhou, China. A G1P1 lady at 39 weeks of gestation was referred to the Huzhong Hospital presenting a fever for two days. She subsequently developed a skin rash on the back and lower limb and at that time she had already experienced five days of fever. She subsequently went into labor and delivered a female neonate weighting 3,500 g at birth. The neonate developed fever on the third day of life which was associated with a systemic erythematous skin rash. There was no report or evidence of mosquito bites after birth. A complete blood count showed leucopenia, thrombocytopenia and anemia and the liver function test showed elevated AST, GGT and bilirubin. Dengue was diagnosed in the mother and the neonate by the ELISA dengue virus NS1 antigen test (Wantai, Beijing, China and dengue virus fluorogenic quantitative PCR test (Liferiver, Shanghai, China.The case report illustrates the possibility of the vertical transmission of dengue. Clinicians should be alert to this possibility and institute early treatment. Further direct evidence and research are required.

  7. Discovery of Dengue Virus NS4B Inhibitors

    Science.gov (United States)

    Wang, Qing-Yin; Dong, Hongping; Zou, Bin; Karuna, Ratna; Wan, Kah Fei; Zou, Jing; Susila, Agatha; Yip, Andy; Shan, Chao; Yeo, Kim Long; Xu, Haoying; Ding, Mei; Chan, Wai Ling; Gu, Feng; Seah, Peck Gee; Liu, Wei; Lakshminarayana, Suresh B.; Kang, CongBao; Lescar, Julien; Blasco, Francesca; Smith, Paul W.

    2015-01-01

    ABSTRACT The four serotypes of dengue virus (DENV-1 to -4) represent the most prevalent mosquito-borne viral pathogens in humans. No clinically approved vaccine or antiviral is currently available for DENV. Here we report a spiropyrazolopyridone compound that potently inhibits DENV both in vitro and in vivo. The inhibitor was identified through screening of a 1.8-million-compound library by using a DENV-2 replicon assay. The compound selectively inhibits DENV-2 and -3 (50% effective concentration [EC50], 10 to 80 nM) but not DENV-1 and -4 (EC50, >20 μM). Resistance analysis showed that a mutation at amino acid 63 of DENV-2 NS4B (a nonenzymatic transmembrane protein and a component of the viral replication complex) could confer resistance to compound inhibition. Genetic studies demonstrate that variations at amino acid 63 of viral NS4B are responsible for the selective inhibition of DENV-2 and -3. Medicinal chemistry improved the physicochemical properties of the initial “hit” (compound 1), leading to compound 14a, which has good in vivo pharmacokinetics. Treatment of DENV-2-infected AG129 mice with compound 14a suppressed viremia, even when the treatment started after viral infection. The results have proven the concept that inhibitors of NS4B could potentially be developed for clinical treatment of DENV infection. Compound 14a represents a potential preclinical candidate for treatment of DENV-2- and -3-infected patients. IMPORTANCE Dengue virus (DENV) threatens up to 2.5 billion people and is now spreading in many regions in the world where it was not previously endemic. While there are several promising vaccine candidates in clinical trials, approved vaccines or antivirals are not yet available. Here we describe the identification and characterization of a spiropyrazolopyridone as a novel inhibitor of DENV by targeting the viral NS4B protein. The compound potently inhibits two of the four serotypes of DENV (DENV-2 and -3) both in vitro and in vivo. Our

  8. Dengue virus-like particles mimic the antigenic properties of the infectious dengue virus envelope.

    Science.gov (United States)

    Metz, Stefan W; Thomas, Ashlie; White, Laura; Stoops, Mark; Corten, Markus; Hannemann, Holger; de Silva, Aravinda M

    2018-04-02

    The 4 dengue serotypes (DENV) are mosquito-borne pathogens that are associated with severe hemorrhagic disease. DENV particles have a lipid bilayer envelope that anchors two membrane glycoproteins prM and E. Two E-protein monomers form head-to-tail homodimers and three E-dimers align to form "rafts" that cover the viral surface. Some human antibodies that strongly neutralize DENV bind to quaternary structure epitopes displayed on E protein dimers or higher order structures forming the infectious virus. Expression of prM and E in cell culture leads to the formation of DENV virus-like particles (VLPs) which are smaller than wildtype virus particles and replication defective due to the absence of a viral genome. There is no data available that describes the antigenic landscape on the surface of flavivirus VLPs in comparison to the better studied infectious virion. A large panel of well characterized antibodies that recognize epitope of ranging complexity were used in biochemical analytics to obtain a comparative antigenic surface view of VLPs in respect to virus particles. DENV patient serum depletions were performed the show the potential of VLPs in serological diagnostics. VLPs were confirmed to be heterogeneous in size morphology and maturation state. Yet, we show that many highly conformational and quaternary structure-dependent antibody epitopes found on virus particles are efficiently displayed on DENV1-4 VLP surfaces as well. Additionally, DENV VLPs can efficiently be used as antigens to deplete DENV patient sera from serotype specific antibody populations. This study aids in further understanding epitopic landscape of DENV VLPs and presents a comparative antigenic surface view of VLPs in respect to virus particles. We propose the use VLPs as a safe and practical alternative to infectious virus as a vaccine and diagnostic antigen.

  9. Neutralization of antibody-enhanced dengue infection by VIS513, a pan serotype reactive monoclonal antibody targeting domain III of the dengue E protein

    Science.gov (United States)

    Robinson, Luke N.; Ong, Li Ching; Rowley, Kirk J.; Winnett, Alexander; Tan, Hwee Cheng; Hobbie, Sven; Shriver, Zachary; Babcock, Gregory J.; Alonso, Sylvie; Ooi, Eng Eong

    2018-01-01

    Dengue virus (DENV) infection imposes enormous health and economic burden worldwide with no approved treatment. Several small molecules, including lovastatin, celgosivir, balapiravir and chloroquine have been tested for potential anti-dengue activity in clinical trials; none of these have demonstrated a protective effect. Recently, based on identification and characterization of cross-serotype neutralizing antibodies, there is increasing attention on the potential for dengue immunotherapy. Here, we tested the ability of VIS513, an engineered cross-neutralizing humanized antibody targeting the DENV E protein domain III, to overcome antibody-enhanced infection and high but brief viremia, which are commonly encountered in dengue patients, in various in vitro and in vivo models. We observed that VIS513 efficiently neutralizes DENV at clinically relevant viral loads or in the presence of enhancing levels of DENV immune sera. Single therapeutic administration of VIS513 in mouse models of primary infection or lethal secondary antibody-enhanced infection, reduces DENV titers and protects from lethal infection. Finally, VIS513 administration does not readily lead to resistance, either in cell culture systems or in animal models of dengue infection. The findings suggest that rapid viral reduction during acute DENV infection with a monoclonal antibody is feasible. PMID:29425203

  10. Viruses infecting reptiles.

    Science.gov (United States)

    Marschang, Rachel E

    2011-11-01

    A large number of viruses have been described in many different reptiles. These viruses include arboviruses that primarily infect mammals or birds as well as viruses that are specific for reptiles. Interest in arboviruses infecting reptiles has mainly focused on the role reptiles may play in the epidemiology of these viruses, especially over winter. Interest in reptile specific viruses has concentrated on both their importance for reptile medicine as well as virus taxonomy and evolution. The impact of many viral infections on reptile health is not known. Koch's postulates have only been fulfilled for a limited number of reptilian viruses. As diagnostic testing becomes more sensitive, multiple infections with various viruses and other infectious agents are also being detected. In most cases the interactions between these different agents are not known. This review provides an update on viruses described in reptiles, the animal species in which they have been detected, and what is known about their taxonomic positions.

  11. Viruses Infecting Reptiles

    Directory of Open Access Journals (Sweden)

    Rachel E. Marschang

    2011-11-01

    Full Text Available A large number of viruses have been described in many different reptiles. These viruses include arboviruses that primarily infect mammals or birds as well as viruses that are specific for reptiles. Interest in arboviruses infecting reptiles has mainly focused on the role reptiles may play in the epidemiology of these viruses, especially over winter. Interest in reptile specific viruses has concentrated on both their importance for reptile medicine as well as virus taxonomy and evolution. The impact of many viral infections on reptile health is not known. Koch’s postulates have only been fulfilled for a limited number of reptilian viruses. As diagnostic testing becomes more sensitive, multiple infections with various viruses and other infectious agents are also being detected. In most cases the interactions between these different agents are not known. This review provides an update on viruses described in reptiles, the animal species in which they have been detected, and what is known about their taxonomic positions.

  12. Chloroquine Inhibits Dengue Virus Type 2 Replication in Vero Cells but Not in C6/36 Cells

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    Kleber Juvenal Silva Farias

    2013-01-01

    Full Text Available Dengue viruses are the most important arthropod-borne viruses in terms of morbidity and mortality in the world. Since there is no dengue vaccine available for human use, we have set out to investigate the use of chloroquine as an antiviral drug against dengue. Chloroquine, an amine acidotropic drug known to affect intracellular exocytic pathways by increasing endosomal pH, was used in the in vitro treatment of Vero and C6/36 cells infected with dengue virus type 2 (DENV-2. Real-time RT-PCR and plaque assays were used to quantify the DENV-2 load in infected Vero and C6/36 cells after chloroquine treatment. Our results showed that a dose of 50 μg/ml of chloroquine was not toxic to the cells and induced a statistically significant inhibition of virus production in infected Vero cells when compared to untreated cells. In C6/36 cells, chloroquine does not induce a statistically significant difference in viral replication when compared to untreated cells, showing that this virus uses an unlikely pathway of penetration in these cells, and results were also confirmed by the plaque assay (PFU. These data suggest that the inhibition of virus infection induced by chloroquine is due to interference with acidic vesicles in mammalian cells.

  13. Chloroquine inhibits dengue virus type 2 replication in Vero cells but not in C6/36 cells.

    Science.gov (United States)

    Farias, Kleber Juvenal Silva; Machado, Paula Renata Lima; da Fonseca, Benedito Antônio Lopes

    2013-01-01

    Dengue viruses are the most important arthropod-borne viruses in terms of morbidity and mortality in the world. Since there is no dengue vaccine available for human use, we have set out to investigate the use of chloroquine as an antiviral drug against dengue. Chloroquine, an amine acidotropic drug known to affect intracellular exocytic pathways by increasing endosomal pH, was used in the in vitro treatment of Vero and C6/36 cells infected with dengue virus type 2 (DENV-2). Real-time RT-PCR and plaque assays were used to quantify the DENV-2 load in infected Vero and C6/36 cells after chloroquine treatment. Our results showed that a dose of 50 μg/ml of chloroquine was not toxic to the cells and induced a statistically significant inhibition of virus production in infected Vero cells when compared to untreated cells. In C6/36 cells, chloroquine does not induce a statistically significant difference in viral replication when compared to untreated cells, showing that this virus uses an unlikely pathway of penetration in these cells, and results were also confirmed by the plaque assay (PFU). These data suggest that the inhibition of virus infection induced by chloroquine is due to interference with acidic vesicles in mammalian cells.

  14. Wolbachia Infection Reduces Blood-Feeding Success in the Dengue Fever Mosquito, Aedes aegypti

    OpenAIRE

    Turley, Andrew P.; Moreira, Luciano A.; O'Neill, Scott L.; McGraw, Elizabeth A.

    2009-01-01

    BACKGROUND: The mosquito Aedes aegypti was recently transinfected with a life-shortening strain of the endosymbiont Wolbachia pipientis (wMelPop) as the first step in developing a biocontrol strategy for dengue virus transmission. In addition to life-shortening, the wMelPop-infected mosquitoes also exhibit increased daytime activity and metabolic rates. Here we sought to quantify the blood-feeding behaviour of Wolbachia-infected females as an indicator of any virulence or energetic drain asso...

  15. Ectoparasitic hematophagous dipters: potential reservoirs of dengue virus?

    Science.gov (United States)

    Setién, Álvaro Aguilar; Baltazar, Anahí García; Leyva, Ignacio Olave; Rojas, Mónica Salas; Koldenkova, Vadim Pérez; García, Mariem Pérez-Peña; Ceballos, Nidia Aréchiga; Romero, Guillermo Gálvez; Villegas, Edgar Olivier López; Malacara, Juan Bibiano Morales; Marín, Cenia Almazán

    2017-01-01

    Recently, the presence of antibodies and dengue virus (DV) RNA in neotropical wild mammals, including Desmodus rotundus, was reported. In a previous study, DV was also found in a high percentage (39.6%) of ectoparasitic hematophagous dipters specifics of these hematophagous bats. In order to verify the susceptibility of these ectoparasites to DV, in this work experimental infections with VD2 of organs explants of Strebla wiedemanni and of Melophagus ovinus were performed using C6/36 cells as control. Viral titers (UFP/mL) were determined at 0, 48 and 96 hrs pi. Infected organs were observed by electron microscopy and under the confocal microscopy indirect immunofluorescence (IIF) using specific conjugates against DV. The infected organs of both species of ectoparasites replicated DV at titers similar to those obtained with the C6/36 cell line (≥10 6 UFP/mL). Electron microscopy and IIF showed DV replication in the digestive tract, tracheoles, reproductive organs of males but not in females, and milk glands (MG) of both species. In the fatty bodies of the MG of M. ovinus, zones with a high affinity for the DV were observed. In this work the susceptibility of S. wiedemanni and M. ovinus to DV was demonstrated and consequently the probable role of this ectoparasites as wild reservoirs of DV. Copyright: © 2017 SecretarÍa de Salud.

  16. Cissampelos pareira Linn: Natural Source of Potent Antiviral Activity against All Four Dengue Virus Serotypes.

    Directory of Open Access Journals (Sweden)

    Ruchi Sood

    2015-12-01

    Full Text Available Dengue, a mosquito-borne viral disease, poses a significant global public health risk. In tropical countries such as India where periodic dengue outbreaks can be correlated to the high prevalence of the mosquito vector, circulation of all four dengue viruses (DENVs and the high population density, a drug for dengue is being increasingly recognized as an unmet public health need.Using the knowledge of traditional Indian medicine, Ayurveda, we developed a systematic bioassay-guided screening approach to explore the indigenous herbal bio-resource to identify plants with pan-DENV inhibitory activity. Our results show that the alcoholic extract of Cissampelos pariera Linn (Cipa extract was a potent inhibitor of all four DENVs in cell-based assays, assessed in terms of viral NS1 antigen secretion using ELISA, as well as viral replication, based on plaque assays. Virus yield reduction assays showed that Cipa extract could decrease viral titers by an order of magnitude. The extract conferred statistically significant protection against DENV infection using the AG129 mouse model. A preliminary evaluation of the clinical relevance of Cipa extract showed that it had no adverse effects on platelet counts and RBC viability. In addition to inherent antipyretic activity in Wistar rats, it possessed the ability to down-regulate the production of TNF-α, a cytokine implicated in severe dengue disease. Importantly, it showed no evidence of toxicity in Wistar rats, when administered at doses as high as 2g/Kg body weight for up to 1 week.Our findings above, taken in the context of the human safety of Cipa, based on its use in Indian traditional medicine, warrant further work to explore Cipa as a source for the development of an inexpensive herbal formulation for dengue therapy. This may be of practical relevance to a dengue-endemic resource-poor country such as India.

  17. Relato de caso: transmissão vertical de dengue Case report: vertical dengue infection

    Directory of Open Access Journals (Sweden)

    Samara L. C. Maroun

    2008-12-01

    Full Text Available OBJETIVOS: Relatar um caso de transmissão vertical de dengue ocorrido durante epidemia de 2008 pelo vírus tipo II no Rio de Janeiro e revisar a literatura sobre transmissão vertical de dengue. DESCRIÇÃO: Relatamos um caso de transmissão vertical de dengue. Recém-nascido a termo do sexo feminino, peso de nascimento de 3.940 g, foi admitida na unidade de terapia intensiva neonatal com rash cutâneo, hipoatividade e febre no quinto dia de vida. O hemograma evidenciava plaquetopenia importante (38.000 plaquetas. A mãe apresentou quadro clínico compatível com dengue 3 dias antes do parto. Foram colhidos então IgM para dengue da mãe e do recém-nascido, realizados pelo método de ELISA, sendo positivos em ambos. Dengue tipo 2 foi detectado no recém-nascido através de reação em cadeia da polimerase. COMENTÁRIOS: Este relato enfatiza a importância do pediatra estar alerta para a possibilidade de transmissão vertical de dengue iniciando precocemente o tratamento.OBJECTIVES: To report a case of vertical dengue infection in a newborn from Rio de Janeiro, Brazil, and to review the literature concerning this problem. DESCRIPTION: We report a case of vertical dengue infection. Female neonate, birth weight 3,940 g, term, was admitted to a neonatal intensive care unit on the fifth day of life with fever and erythematous rash. Her mother had had dengue fever 3 days before delivery. Her platelet count was 38,000, dropping to 15,000. She did not have any hemorrhagic episodes, including cerebral hemorrhages. Anti-dengue antibodies (IgM were positive in the mother and infant. Dengue type 2 was detected in the infant using polymerase chain reaction. COMMENTS: This report emphasizes that pediatricians should be aware of the possibility of vertical dengue infection so that early management can be instituted.

  18. Non-Canonical Roles of Dengue Virus Non-Structural Proteins

    Directory of Open Access Journals (Sweden)

    Julianna D. Zeidler

    2017-03-01

    Full Text Available The Flaviviridae family comprises a number of human pathogens, which, although sharing structural and functional features, cause diseases with very different outcomes. This can be explained by the plurality of functions exerted by the few proteins coded by viral genomes, with some of these functions shared among members of a same family, but others being unique for each virus species. These non-canonical functions probably have evolved independently and may serve as the base to the development of specific therapies for each of those diseases. Here it is discussed what is currently known about the non-canonical roles of dengue virus (DENV non-structural proteins (NSPs, which may account for some of the effects specifically observed in DENV infection, but not in other members of the Flaviviridae family. This review explores how DENV NSPs contributes to the physiopathology of dengue, evasion from host immunity, metabolic changes, and redistribution of cellular components during infection.

  19. Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics

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    George Savidis

    2016-06-01

    Full Text Available The flaviviruses dengue virus (DENV and Zika virus (ZIKV are severe health threats with rapidly expanding ranges. To identify the host cell dependencies of DENV and ZIKV, we completed orthologous functional genomic screens using RNAi and CRISPR/Cas9 approaches. The screens recovered the ZIKV entry factor AXL as well as multiple host factors involved in endocytosis (RAB5C and RABGEF, heparin sulfation (NDST1 and EXT1, and transmembrane protein processing and maturation, including the endoplasmic reticulum membrane complex (EMC. We find that both flaviviruses require the EMC for their early stages of infection. Together, these studies generate a high-confidence, systems-wide view of human-flavivirus interactions and provide insights into the role of the EMC in flavivirus replication.

  20. A Simple Reverse Transcription-Polymerase Chain Reaction for Dengue Type 2 Virus Identification

    Directory of Open Access Journals (Sweden)

    Luiz Tadeu M Figueiredo

    1997-05-01

    Full Text Available We show here a simplified reverse transcription-polymerase chain reaction (RT-PCR for identification of dengue type 2 virus. Three dengue type 2 virus strains, isolated from Brazilian patients, and yellow fever vaccine 17DD, as a negative control, were used in this study. C6/36 cells were infected with the virus, and tissue culture fluids were collected after 7 days of infection period. The RT-PCR, a combination of RT and PCR done after a single addition of reagents in a single reaction vessel was carried out following a digestion of virus with 1% Nonidet P-40. The 50ml assay reaction mixture included 50 pmol of a dengue type 2 specific primer pair amplifying a 210 base pair sequence of the envelope protein gene, 0.1 mM of the four deoxynucleoside triphosphates, 7.5U of reverse transcriptase, and 1U of thermostable Taq DNA polymerase. The reagent mixture was incubated for 15 min at 37oC for RT followed by a variable amount of cycles of two-step PCR amplification (92oC for 60 sec, 53oC for 60 sec with slow temperature increment. The PCR products were subjected to 1.7% agarose gel electrophoresis and visualized with UV light after gel incubation in ethidium bromide solution. DNA bands were observed after 25 and 30 cycles of PCR. Virus amount as low as 102.8 TCID50/ml was detected by RT-PCR. Specific DNA amplification was observed with the three dengue type 2 strains. This assay has advantages compared to other RT-PCRs: it avoids laborious extraction of virus RNA; the combination of RT and PCR reduces assay time, facilitates the performance and reduces risk of contamination; the two-step PCR cycle produces a clear DNA amplification, saves assay time and simplifies the technique

  1. Dengue virus serological prevalence and seroconversion rates in children and adults in Medellin, Colombia: implications for vaccine introduction.

    Science.gov (United States)

    Carabali, Mabel; Lim, Jacqueline Kyungah; Velez, Diana Carolina; Trujillo, Andrea; Egurrola, Jorge; Lee, Kang Sung; Kaufman, Jay S; DaSilva, Luiz Jacinto; Velez, Ivan Dario; Osorio, Jorge E

    2017-05-01

    Dengue is an important public health problem worldwide. A vaccine has recently been licensed in some countries of Latin America and Asia. Recommendations for dengue vaccine introduction include endemicity and a high serological prevalence of dengue in the territories considering its introduction. A community-based survey was conducted to estimate dengue seroprevalence and age-specific seroconversion rates in a community in Medellin, Colombia, using a dengue serological test (IgG indirect ELISA). Residents were selected at random and were first screened for dengue infection; they were then followed over 2.5 years. A total of 3684 individuals aged between 1 and 65 years participated in at least one survey. The overall dengue seroprevalence was 61%, and only 3.3% of seropositive subjects self-reported a past history of dengue. Among dengue virus (DENV)-naïve subjects with more than two visits (n=1002), the overall seroconversion rate was 8.7% (95% confidence interval 7.3-10.4) per 1000 person-months, over the study period. Overall, the mean age of DENV prevalent subjects was significantly higher than the mean age of seroconverted subjects. Specifically, DENV seropositivity over 70% was observed in participants over 21 years old. Serotype-specific plaque-reduction neutralization tests (PRNT) revealed that all four dengue serotypes were circulating, with DENV4 being most prevalent. These laboratory-based findings could inform dengue vaccine decisions, as they provide age-specific seroprevalence and seroconversion data, evidencing permanent and ongoing dengue transmission in the study area. This study provides evidence for the existing rates of secondary and heterotypic responses, presenting a challenge that must be addressed adequately by the new vaccine candidates. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  2. Dengue infection severity score – improvised disease management

    Directory of Open Access Journals (Sweden)

    Mahmood SU

    2016-08-01

    Full Text Available Syed Uzair Mahmood,1 Maryam Jamil Syed,1 Aisha Jamal,1 Maria Shoaib2 1Sindh Medical College, Jinnah Sindh Medical University, Karachi, Pakistan; 2Dow Medical College, Dow University of Health Sciences, Karachi, PakistanWe would like to add our views regarding the paper “Validation of Dengue infection severity score” by Pongpan et al.1 As the paper outlines, the purpose of the Dengue Severity Score is to classify individuals with dengue infection into three levels of severity with clinically acceptable underestimation or overestimation. View the original paper by Pongpan and colleagues. 

  3. Neonatal-onset hemophagocytic lymphohistiocytosis associated with primary dengue infection

    Directory of Open Access Journals (Sweden)

    Madhumita Nandi

    2016-01-01

    Full Text Available A 40-day-old baby presented with prolonged fever, petechial spots, hepatosplenomegaly, generalized lymphadenopathy, and pancytopenia. Investigations revealed positive anti-dengue virus IgM antibody, and bone marrow examination demonstrated the presence of hemophagocytes. The diagnosis of hemophagocytic lymphohistiocytosis (HLH was made according to HLH-2004 guidelines. HLH associated with primary dengue in an infant who was symptomatic from neonatal age has hitherto not been reported in the literature.

  4. Consequences of the expanding global distribution of Aedes albopictus for dengue virus transmission.

    Directory of Open Access Journals (Sweden)

    Louis Lambrechts

    2010-05-01

    Full Text Available The dramatic global expansion of Aedes albopictus in the last three decades has increased public health concern because it is a potential vector of numerous arthropod-borne viruses (arboviruses, including the most prevalent arboviral pathogen of humans, dengue virus (DENV. Ae. aegypti is considered the primary DENV vector and has repeatedly been incriminated as a driving force in dengue's worldwide emergence. What remains unresolved is the extent to which Ae. albopictus contributes to DENV transmission and whether an improved understanding of its vector status would enhance dengue surveillance and prevention. To assess the relative public health importance of Ae. albopictus for dengue, we carried out two complementary analyses. We reviewed its role in past dengue epidemics and compared its DENV vector competence with that of Ae. aegypti. Observations from "natural experiments" indicate that, despite seemingly favorable conditions, places where Ae. albopictus predominates over Ae. aegypti have never experienced a typical explosive dengue epidemic with severe cases of the disease. Results from a meta-analysis of experimental laboratory studies reveal that although Ae. albopictus is overall more susceptible to DENV midgut infection, rates of virus dissemination from the midgut to other tissues are significantly lower in Ae. albopictus than in Ae. aegypti. For both indices of vector competence, a few generations of mosquito colonization appear to result in a relative increase of Ae. albopictus susceptibility, which may have been a confounding factor in the literature. Our results lead to the conclusion that Ae. albopictus plays a relatively minor role compared to Ae. aegypti in DENV transmission, at least in part due to differences in host preferences and reduced vector competence. Recent examples of rapid arboviral adaptation to alternative mosquito vectors, however, call for cautious extrapolation of our conclusion. Vector status is a dynamic

  5. Weather Regulates Location, Timing, and Intensity of Dengue Virus Transmission between Humans and Mosquitoes

    OpenAIRE

    Campbell, Karen M.; Haldeman, Kristin; Lehnig, Chris; Munayco, Cesar V.; Halsey, Eric S.; Laguna-Torres, V. Alberto; Yagui, Mart?n; Morrison, Amy C.; Lin, Chii-Dean; Scott, Thomas W.

    2015-01-01

    Background Dengue is one of the most aggressively expanding mosquito-transmitted viruses. The human burden approaches 400 million infections annually. Complex transmission dynamics pose challenges for predicting location, timing, and magnitude of risk; thus, models are needed to guide prevention strategies and policy development locally and globally. Weather regulates transmission-potential via its effects on vector dynamics. An important gap in understanding risk and roadblock in model devel...

  6. Development and evaluation of one step single tube multiplex RT-PCR for rapid detection and typing of dengue viruses

    Directory of Open Access Journals (Sweden)

    Parida Manmohan

    2008-01-01

    Full Text Available Abstract Background Dengue is emerging as a major public health concern in many parts of the world. The development of a one-step, single tube, rapid, and multiplex reverse transcription polymerase chain reaction (M-RT-PCR for simultaneous detection and typing of dengue virus using serotype specific primers during acute phase of illness is reported. Results An optimal assay condition with zero background was established having no cross-reaction with closely related members of flavivirus (Japanese encephalitis, West Nile, Yellow fever and alphavirus (Chikungunya. The feasibility of M-RT-PCR assay for clinical diagnosis was validated with 620 acute phase dengue patient sera samples of recent epidemics in India. The comparative evaluation vis a vis conventional virus isolation revealed higher sensitivity. None of the forty healthy serum samples screened in the present study revealed any amplification, thereby establishing specificity of the reported assay for dengue virus only. Conclusion These findings clearly suggested that M-RT-PCR assay reported in the present study is the rapid and cost-effective method for simultaneous detection as well as typing of the dengue virus in acute phase patient serum samples. Thus, the M-RT-PCR assay developed in this study will serve as a very useful tool for rapid diagnosis and typing of dengue infections in endemic areas.

  7. Novel vaccination approach for dengue infection based on recombinant immune complex universal platform.

    Science.gov (United States)

    Kim, Mi-Young; Reljic, Rajko; Kilbourne, Jacquelyn; Ceballos-Olvera, Ivonne; Yang, Moon-Sik; Reyes-del Valle, Jorge; Mason, Hugh S

    2015-04-08

    Dengue infection is on the rise in many endemic areas of the tropics. Vaccination remains the most realistic strategy for prevention of this potentially fatal viral disease but there is currently no effective vaccine that could protect against all four known serotypes of the dengue virus. This study describes the generation and testing of a novel vaccination approach against dengue based on recombinant immune complexes (RIC). We modelled the dengue RIC on the existing Ebola RIC (Phoolcharoen, et al. Proc Natl Acad Sci USA 2011;108(Dec (51)):20695) but with a key modification that allowed formation of a universal RIC platform that can be easily adapted for use for other pathogens. This was achieved by retaining only the binding epitope of the 6D8 ant-Ebola mAb, which was then fused to the consensus dengue E3 domain (cEDIII), resulting in a hybrid dengue-Ebola RIC (DERIC). We expressed human and mouse versions of these molecules in tobacco plants using a geminivirus-based expression system. Following purification from the plant extracts by protein G affinity chromatography, DERIC bound to C1q component of complement, thus confirming functionality. Importantly, following immunization of mice, DERIC induced a potent, virus-neutralizing anti-cEDIII humoral immune response without exogenous adjuvants. We conclude that these self-adjuvanting immunogens have the potential to be developed as a novel vaccine candidate for dengue infection, and provide the basis for a universal RIC platform for use with other antigens. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. A small molecule fusion inhibitor of dengue virus

    NARCIS (Netherlands)

    Poh, Mee Kian; Yip, Andy; Zhang, Summer; Priestle, John P.; Ma, Ngai Ling; Smit, Jolanda M.; Wischut, Jan; Shi, Pei-Yong; Wenk, Markus R.; Schul, Wouter

    2009-01-01

    The dengue virus envelope protein plays an essential role in viral entry by mediating fusion between the viral and host membranes. The crystal structure of the envelope protein shows a pocket (located at a "hinge" between Domains I and II) that can be occupied by ligand n-octyl-beta-D-glucoside

  9. Comparison analysis of microRNAs in response to dengue virus type 2 infection between the Vero cell-adapted strain and its source, the clinical C6/36 isolated strain.

    Science.gov (United States)

    Yang, Jiajia; Lin, Yao; Jiang, Liming; Xi, Juemin; Wang, Xiaodan; Guan, Jiaoqiong; Chen, Junying; Pan, Yue; Luo, Jia; Ye, Chao; Sun, Qiangming

    2018-05-02

    To elucidate the differences in microRNAs during dengue virus infection between Vero cell-adapted strain (DENV-2-Vero) and its source, the clinical C6/36 isolated strain (DENV-2-C6/36), a comparison analysis was performed in Vero cells by high throughput sequencing. The results showed that the expression of 16 known and 3 novel miRNAs exhibited marked differences. 5 known miRNAs were up-regulated in DENV-2-C6/36 group, while 11 known microRNAs were down-regulated in DENV-2-Vero group. The GO enrichment and KEGG pathway analysis showed that there was a distinct difference in regulating viral replication between two strains. In DENV-2-Vero infection group, significantly enriched GO terms included virion attachment to host cells, viral structural protein/genome processing and packaging. Meanwhile, the regulation of cell death and apoptosis between two groups were different in the early stage of infection. KEGG enrichment analysis showed that DENV-2-C6/36 infection induced more intense regulation of immune-related pathways, including Fc gamma R-mediated phagocytosis, etc. DENV-2-Vero infection could partially alleviate the immune defense of Vero cells compared with DENV-2-C6/36. The results indicated that the distinct microRNA changes induced by two DENV-2 strains may be partly related to their infective abilities. Our data provide useful insights that help elucidate the host-pathogen interactions following DENV infection. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Post encephalitic parkinsonism following dengue viral infection

    OpenAIRE

    Bopeththa, B. V. K. M.; Ralapanawa, U.

    2017-01-01

    Background Incidence of dengue fever as well as dengue hemorrhagic fever is increasing in Sri Lanka especially among elderly population. As the number of cases is rising, rare complications of dengue illness also can be seen in clinical practice when compared to the past few years. Prompt identification and treatment of such complications is challenging due to lack of awareness and unavailability of standard treatment. Case presentation 69 years old man presented with acute onset fever and wa...

  11. Multi-level analyses of spatial and temporal determinants for dengue infection.

    Science.gov (United States)

    Vanwambeke, Sophie O; van Benthem, Birgit H B; Khantikul, Nardlada; Burghoorn-Maas, Chantal; Panart, Kamolwan; Oskam, Linda; Lambin, Eric F; Somboon, Pradya

    2006-01-18

    Dengue is a mosquito-borne viral infection that is now endemic in most tropical countries. In Thailand, dengue fever/dengue hemorrhagic fever is a leading cause of hospitalization and death among children. A longitudinal study among 1750 people in two rural and one urban sites in northern Thailand from 2001 to 2003 studied spatial and temporal determinants for recent dengue infection at three levels (time, individual and household). Determinants for dengue infection were measured by questionnaire, land-cover maps and GIS. IgM antibodies against dengue were detected by ELISA. Three-level multi-level analysis was used to study the risk determinants of recent dengue infection. Rates of recent dengue infection varied substantially in time from 4 to 30%, peaking in 2002. Determinants for recent dengue infection differed per site. Spatial clustering was observed, demonstrating variation in local infection patterns. Most of the variation in recent dengue infection was explained at the time-period level. Location of a person and the environment around the house (including irrigated fields and orchards) were important determinants for recent dengue infection. We showed the focal nature of asymptomatic dengue infections. The great variation of determinants for recent dengue infection in space and time should be taken into account when designing local dengue control programs.

  12. Multi-level analyses of spatial and temporal determinants for dengue infection

    Directory of Open Access Journals (Sweden)

    Oskam Linda

    2006-01-01

    Full Text Available Abstract Background Dengue is a mosquito-borne viral infection that is now endemic in most tropical countries. In Thailand, dengue fever/dengue hemorrhagic fever is a leading cause of hospitalization and death among children. A longitudinal study among 1750 people in two rural and one urban sites in northern Thailand from 2001 to 2003 studied spatial and temporal determinants for recent dengue infection at three levels (time, individual and household. Methods Determinants for dengue infection were measured by questionnaire, land-cover maps and GIS. IgM antibodies against dengue were detected by ELISA. Three-level multi-level analysis was used to study the risk determinants of recent dengue infection. Results Rates of recent dengue infection varied substantially in time from 4 to 30%, peaking in 2002. Determinants for recent dengue infection differed per site. Spatial clustering was observed, demonstrating variation in local infection patterns. Most of the variation in recent dengue infection was explained at the time-period level. Location of a person and the environment around the house (including irrigated fields and orchards were important determinants for recent dengue infection. Conclusion We showed the focal nature of asymptomatic dengue infections. The great variation of determinants for recent dengue infection in space and time should be taken into account when designing local dengue control programs.

  13. Targeting Dengue Virus NS-3 Helicase by Ligand based Pharmacophore Modeling and Structure based Virtual Screening

    Science.gov (United States)

    Halim, Sobia A.; Khan, Shanza; Khan, Ajmal; Wadood, Abdul; Mabood, Fazal; Hussain, Javid; Al-Harrasi, Ahmed

    2017-10-01

    Dengue fever is an emerging public health concern, with several million viral infections occur annually, for which no effective therapy currently exist. Non-structural protein 3 (NS-3) Helicase encoded by the dengue virus (DENV) is considered as a potential drug target to design new and effective drugs against dengue. Helicase is involved in unwinding of dengue RNA. This study was conducted to design new NS-3 Helicase inhibitor by in silico ligand- and structure based approaches. Initially ligand-based pharmacophore model was generated that was used to screen a set of 1201474 compounds collected from ZINC Database. The compounds matched with the pharmacophore model were docked into the active site of NS-3 helicase. Based on docking scores and binding interactions, twenty five compounds are suggested to be potential inhibitors of NS3 Helicase. The pharmacokinetic properties of these hits were predicted. The selected hits revealed acceptable ADMET properties. This study identified potential inhibitors of NS-3 Helicase in silico, and can be helpful in the treatment of Dengue.

  14. Dengue Virus Capsid Protein Binds Core Histones and Inhibits Nucleosome Formation in Human Liver Cells

    Science.gov (United States)

    Colpitts, Tonya M.; Barthel, Sebastian; Wang, Penghua; Fikrig, Erol

    2011-01-01

    Dengue virus (DENV) is a member of the Flaviviridae and a globally (re)emerging pathogen that causes serious human disease. There is no specific antiviral or vaccine for dengue virus infection. Flavivirus capsid (C) is a structural protein responsible for gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. Flaviviral replication is known to occur in the cytoplasm yet a large portion of capsid protein localizes to the nucleus during infection. The reasons for the nuclear presences of capsid are not completely understood. Here, we expressed mature DENV C in a tandem affinity purification assay to identify potential binding partners in human liver cells. DENV C targeted the four core histones, H2A, H2B, H3 and H4. DENV C bound recombinant histones in solution and colocalized with histones in the nucleus and cytoplasm of liver cells during DENV infection. We show that DENV C acts as a histone mimic, forming heterodimers with core histones, binding DNA and disrupting nucleosome formation. We also demonstrate that DENV infection increases the amounts of core histones in livers cells, which may be a cellular response to C binding away the histone proteins. Infection with DENV additionally alters levels of H2A phosphorylation in a time-dependent manner. The interactions of C and histones add an interesting new role for the presence of C in the nucleus during DENV infection. PMID:21909430

  15. Dengue infection associated hemophagocytic syndrome: Therapeutic interventions and outcome.

    Science.gov (United States)

    Wan Jamaludin, Wan Fariza; Periyasamy, Petrick; Wan Mat, Wan Rahiza; Abdul Wahid, S Fadilah

    2015-08-01

    Infection associated hemophagocytic syndrome is increasingly recognized as a potentially fatal complication of dengue fever. It should be suspected with prolonged fever beyond seven days associated with hepatosplenomegaly, hyperferritinemia, worsening cytopenias and development of multiorgan dysfunction. Surge of similar pro-inflammatory cytokines observed in dengue associated hemophagocytic syndrome and multiorgan dysfunction may indicate they are part of related inflammatory spectrum. A proportion of patients recovered with supportive therapy, however most required interventions with corticosteroids, intravenous immunoglobulin or chemotherapy. We report three cases of dengue associated IAHS with good outcome following early recognition and treatment with dexamethasone and intravenous immunoglobulin. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Olive baboons: a non-human primate model for testing dengue virus type 2 replication.

    Science.gov (United States)

    Valdés, Iris; Gil, Lázaro; Castro, Jorge; Odoyo, Damián; Hitler, Rikoi; Munene, Elephas; Romero, Yaremis; Ochola, Lucy; Cosme, Karelia; Kariuki, Thomas; Guillén, Gerardo; Hermida, Lisset

    2013-12-01

    This study evaluated the use of a non-human primate, the olive baboon (Papio anubis), as a model of dengue infection. Olive baboons closely resemble humans genetically and physiologically and have been used extensively for assessing novel vaccine formulations. Two doses of dengue virus type 2 (DENV-2) were tested in baboons: 10(3) and 10(4) pfu. Similarly, African green monkeys received the same quantity of virus and acted as positive controls. Following exposure, high levels of viremia were detected in both animal species. There was a trend to detect more days of viremia and more homogeneous viral titers in animals receiving the low viral dose. In addition, baboons infected with the virus generally exhibited positive virus isolation 1 day later than African green monkeys. Humoral responses consisting of antiviral and neutralizing antibodies were detected in all animals after infection. We conclude that baboons provide an alternative non-human primate species for experimental DENV-2 infection and we recommend their use for further tests of vaccines, administering the lowest dose assayed: 10(3) pfu. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  17. Novel benzoxazole inhibitor of dengue virus replication that targets the NS3 helicase.

    Science.gov (United States)

    Byrd, Chelsea M; Grosenbach, Douglas W; Berhanu, Aklile; Dai, Dongcheng; Jones, Kevin F; Cardwell, Kara B; Schneider, Christine; Yang, Guang; Tyavanagimatt, Shanthakumar; Harver, Chris; Wineinger, Kristin A; Page, Jessica; Stavale, Eric; Stone, Melialani A; Fuller, Kathleen P; Lovejoy, Candace; Leeds, Janet M; Hruby, Dennis E; Jordan, Robert

    2013-04-01

    Dengue virus (DENV) is the predominant mosquito-borne viral pathogen that infects humans with an estimated 50 to 100 million infections per year worldwide. Over the past 50 years, the incidence of dengue disease has increased dramatically and the virus is now endemic in more than 100 countries. Moreover, multiple serotypes of DENV are now found in the same geographic region, increasing the likelihood of more severe forms of disease. Despite extensive research, there are still no approved vaccines or therapeutics commercially available to treat DENV infection. Here we report the results of a high-throughput screen of a chemical compound library using a whole-virus assay that identified a novel small-molecule inhibitor of DENV, ST-610, that potently and selectively inhibits all four serotypes of DENV replication in vitro. Sequence analysis of drug-resistant virus isolates has identified a single point mutation, A263T, in the NS3 helicase domain that confers resistance to this compound. ST-610 inhibits DENV NS3 helicase RNA unwinding activity in a molecular-beacon-based helicase assay but does not inhibit nucleoside triphosphatase activity based on a malachite green ATPase assay. ST-610 is nonmutagenic, is well tolerated (nontoxic) in mice, and has shown efficacy in a sublethal murine model of DENV infection with the ability to significantly reduce viremia and viral load compared to vehicle controls.

  18. Effects of Larval Nutrition on Wolbachia-Based Dengue Virus Interference in Aedes aegypti (Diptera: Culicidae).

    Science.gov (United States)

    Kho, Elise A; Hugo, Leon E; Lu, Guangjin; Smith, David D; Kay, Brian H

    2016-07-01

    In order to assess the broad-scale applicability of field releases of Wolbachia for the biological control of insect-transmitted diseases, we determined the relationship between the larval diet of Aedes aegypti L. mosquitoes infected with Wolbachia strains and their susceptibility to dengue virus (DENV) infection via intrathoracic injection and oral inoculation. Larvae were reared on diets that varied in the quantity of food which had the effect of modifying development time and adult body size. Wolbachia wMel infection was associated with highly significant reductions in dengue serotype 2 (DENV-2) infection rates of between 80 and 97.5% following intrathoracic injection of adults emerging from three diet levels. Reductions were 100% in two diet level treatments following oral inoculation. Similarly, wMelPop infection was associated with highly significant reductions in DENV-2 infection rates of between 95 and 100% for intrathoracic injection and 97.5 and 100% for oral inoculation across diet level treatments. Larval diet level had no significant effect on DENV-2 infection rates in the presence of Wolbachia infection in mosquitoes that were intrathoracically injected with the virus. This indicates that the effectiveness of Wolbachia on vector competence disruption within Ae. aegypti is unlikely to be compromised by variable larval nutrition in field settings. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Temperature modulates dengue virus epidemic growth rates through its effects on reproduction numbers and generation intervals.

    Science.gov (United States)

    Siraj, A. S.; Oidtman, R. J.; Huber, J. H.; Kraemer, M. U.; Brady, O. J.; Johansson, M. A.; Perkins, T. A.

    2017-12-01

    Epidemic growth rate, r, provides a more complete description of the potential for epidemics than the more commonly studied basic reproduction number, R0, yet the former has never been described as a function of temperature for dengue virus or other pathogens with temperature-sensitive transmission. The need to understand the drivers of epidemics of these pathogens is acute, with arthropod-borne virus epidemics becoming increasingly problematic. We addressed this need by developing temperature-dependent descriptions of the two components of r—R0 and the generation interval—to obtain a temperature-dependent description of r. Our results show that the generation interval is highly sensitive to temperature, decreasing twofold between 25 and 35 °C and suggesting that dengue virus epidemics may accelerate as temperatures increase, not only because of more infections per generation but also because of faster generations. Under the empirical temperature relationships that we considered, we found that r peaked at a temperature threshold that was robust to uncertainty in model parameters that do not depend on temperature. Although the precise value of this temperature threshold could be refined following future studies of empirical temperature relationships, the framework we present for identifying such temperature thresholds offers a new way to classify regions in which dengue virus epidemic intensity could either increase or decrease under future climate change.

  20. Phylogenetic Analysis of Dengue Virus in Bangkalan, Madura Island, East Java Province, Indonesia.

    Science.gov (United States)

    Sucipto, Teguh Hari; Kotaki, Tomohiro; Mulyatno, Kris Cahyo; Churrotin, Siti; Labiqah, Amaliah; Soegijanto, Soegeng; Kameoka, Masanori

    2018-01-01

    Dengue virus (DENV) infection is a major health issue in tropical and subtropical areas. Indonesia is one of the biggest dengue endemic countries in the world. In the present study, the phylogenetic analysis of DENV in Bangkalan, Madura Island, Indonesia, was performed in order to obtain a clearer understanding of its dynamics in this country. A total of 359 blood samples from dengue-suspected patients were collected between 2012 and 2014. Serotyping was conducted using a multiplex Reverse Transcriptase-Polymerase Chain Reaction and a phylogenetic analysis of E gene sequences was performed using the Bayesian Markov chain Monte Carlo (MCMC) method. 17 out of 359 blood samples (4.7%) were positive for the isolation of DENV. Serotyping and the phylogenetic analysis revealed the predominance of DENV-1 genotype I (9/17, 52.9%), followed by DENV-2 Cosmopolitan type (7/17, 41.2%) and DENV-3 genotype I (1/17, 5.9%) . DENV-4 was not isolated. The Madura Island isolates showed high nucleotide similarity to other Indonesian isolates, indicating frequent virus circulation in Indonesia. The results of the present study highlight the importance of continuous viral surveillance in dengue endemic areas in order t