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

PeerJ ◽  
2018 ◽  
Vol 5 ◽  
pp. e3939 ◽  
Author(s):  
Wei-Lian Tan ◽  
Yean Kee Lee ◽  
Yen Fong Ho ◽  
Rohana Yusof ◽  
Noorsaadah Abdul Rahman ◽  
...  
Keyword(s):  
Virus Infection ◽  
Dengue Virus ◽  
Viral Infection ◽  
Dengue Infection ◽  
Functional Characterization ◽  
Denv Infection ◽  
Comparative Proteomics ◽  
Therapeutic Drug ◽  
Synthetic Analogue ◽  
Down Regulation

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.

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

mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Vivian Vasconcelos Costa ◽  
Weijian Ye ◽  
Qingfeng Chen ◽  
Mauro Martins Teixeira ◽  
Peter Preiser ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Virus Infection ◽  
Dengue Virus ◽  
Nk Cells ◽  
Adhesion Molecules ◽  
Cell Activation ◽  
Nk Cell ◽  
Denv Infection ◽  
Ifn Γ

ABSTRACT 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 virus infection. These results show a critical role of human NK cells in controlling DENV infection in vivo and reveal the sequence of molecular and cellular events that activate NK cells to control dengue virus 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 virus infection. These results show a critical role of human NK cells in controlling DENV infection in vivo and reveal the sequence of molecular and cellular events that activate NK cells to control dengue virus infection.

scholarly journals NS-1 antigen positive Dengue Infection and molecular characterization of Dengue Viruses in a private Medical College Hospitalin Dhaka, Bangladesh

2018 ◽  
Vol 17 (4) ◽  
pp. 669-673
Author(s):  
Mahmuda Siddiqua ◽  
Ahmed Nawsher Alam ◽  
AKM Muraduzzaman ◽  
Tahmina Shirin
Keyword(s):  
Virus Infection ◽  
Dengue Virus ◽  
Dengue Infection ◽  
Medical Science ◽  
Cost Effective ◽  
Rt Pcr ◽  
Dengue Virus Infection ◽  
Medical College ◽  
Virus Serotype ◽  
Ns1 Antigen

Introduction: Detection of dengue virus infection as soon as possible is critical for management of dengue virus infected patients. Immuno-chromatographic (ICT) tests are easy, cost effective method for dengue virus antigen detection.The sensitivity and specificity of ICT should compare with a gold standard test like RT-PCR. Aim of this study was to compare two test methods (ICT and RT-PCR), observe dengue serotype and seasonal impact on dengue infection.Methodology & result: The patients of Ibn Sina Medical College Hospital from October 2015 to October 2017 were tested for dengue NS1 antigen by ICT method. Out of 3201 sample tested 32.39% were found positive and 89 of which were re-tested for RT-PCR for comparison. Eighty eight of 89 NS1 positive cases showed positive by RT-PCR method giving an accuracy of 98.87%. Among the RT-PCR positive cases 45 were further analyzed for serotype. DEN-1, DEN-2 or both DEN- 1 and DEN-2 were found in 21, 23 and 1cases respectively. No cases of DEN-3 or DEN-4 were detected.Conclusion: This study showed that easily available and cost effective dengue NS1 antigen detection method (ICT) is as effective as molecular test (RT-PCR). DEN-1 and DEN-2 serotype were prevalent during last few years in Bangladesh. Continuous monitoring of dengue virus serotype is important for prevention and control of sudden epidemic by other serotype. Alert to be more during post monsoon when the peak of dengue virus infection was observed.Bangladesh Journal of Medical Science Vol.17(4) 2018 p.669-673

A SPATIAL CLUSTERING APPROACH TO IDENTIFY RISK AREAS OF DENGUE INFECTION AFTER INSECTICIDE SPRAYING

2016 ◽  
Vol 78 (5-3) ◽  
Author(s):  
Napadol Sudsom ◽  
Suwich Thammapalo ◽  
Theerakamol Pengsakul ◽  
Kuaanan Techato
Keyword(s):  
Virus Infection ◽  
Dengue Virus ◽  
Spatial Clustering ◽  
Dengue Infection ◽  
Spatial Association ◽  
Dengue Vector ◽  
Dengue Virus Infection ◽  
Spatial Analyst ◽  
Risk Areas ◽  
Clustering Approach

This study aims to demonstrate a spatial clustering approach for identifying risk households of dengue virus infection during the period of insecticide spraying-ultra low volume (ULV). All households located within 100 m radius of spraying area were recorded with geographic coordinates and divide into three groups of spraying (unsprayed, only outdoor and indoor plus outdoor sprayed house). A total of 45 households with geographic coordinates, were randomly selected to monitor ovitrap index, the percentage of positive ovitraps and the number of eggs per trap, in pre- and post-ULV spraying. Application of spatial analyst tools and spatial statistics tools in ArcGIS 10.1 were used to determine mosquito density and identify risk households using ovitrap index. The prediction maps of Aedes aegypti vector abundance were illustrated by kriging technique. Base on the results, the cluster of Ae. aegypti populations were detected on four day after the spraying. This finding shows the significant spatial pattern of dengue vector populations which may cause high risk areas of dengue virus infection after insecticide treatment. This methodological framework could be used for improving the strategy of dengue vector and outbreak control. The spatial association between dengue vector and the coverage of space spraying requires further study.

Neonate with haemophagocytic lymphohistiocytosis secondary to dengue infection: a case report

2016 ◽  
Vol 47 (3) ◽  
pp. 253-255 ◽  
Author(s):  
MV Krithika ◽  
Prakash Amboiram ◽  
Sneha M Latha ◽  
Binu Ninan ◽  
Febe Renjitha Suman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Case Report ◽  
Virus Infection ◽  
Dengue Virus ◽  
Dengue Infection ◽  
Haemophagocytic Lymphohistiocytosis ◽  
Dengue Virus Infection ◽  
The Third ◽  
First Case

We report the first case of haemophagocytic lymphohistiocytosis (HLH) in a neonate secondary to primary Dengue virus infection. This neonate presented in the third week of life with fever, shock and hepatosplenomegaly and was diagnosed to have Dengue infection by serology and HLH was confirmed on bone marrow.

High Incidence of Peripheral Blood Plasmacytosis In Patients with Dengue Virus Infection: a Prospective Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2772-2772
Author(s):  
Khao T.D. Thai ◽  
Josta A. Wismeijer ◽  
Catrien M. Zumpolle ◽  
Menno D. de Jong ◽  
Peter J. Vde ries ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Viral Load ◽  
Dengue Virus ◽  
Peripheral Blood ◽  
Extreme Values ◽  
Conflicts Of Interest ◽  
Dengue Infection ◽  
Denv Infection ◽  
Bone Marrow Suppression ◽  
Median Percentage

Abstract Abstract 2772 Introduction: One of the characteristic features of dengue virus (DENV) infection is the occurrence of leukopenia and thrombocytopenia, probably resulting from virus induced bone marrow suppression. Despite the general bone marrow suppression, polyclonal peripheral blood plasmacytosis has occasionally been described in DENV infected patients. The frequency of peripheral blood (PB) plasmacytosis in patients with dengue infection, the origin of these plasma cells (PCs) and the mechanisms by which they appear in the blood are not known. We initiated this prospective observational study to quantify and describe the kinetics and phenotype of PB plasmacells (PCs) in these patients. Methods: Morphological examination of the peripheral blood smear was performed in 35 sequential returned travelers suspected of DENV infection, with a history of less than 14 days of fever. Flow cytometric (FC) analysis for the characterization and immunophenotyping of lymphocyte subsets and PCs was performed in 31 patients. Follow-up samples were available for 8 patients. Results: Our results show that PB plasmacytosis is a very common hematological finding in DENV infection, with extreme values of up to 36% of total white blood cells in some patients. Depending on the number of days since the onset of fever at presentation, PB plasmacytosis was observed in 64% to 73% of 28 patients with confirmed DENV infection, and in none of 7 patients with other febrile illnesses. PB plasmacytosis was the most pronounced before 7 days after onset of illness and declined rapidly thereafter, to completely disappear after 14 days of illness. The median percentage of PCs at day 7 was 2.5% (range 0–36%; 25–75 interquartile range: 0–8%). The median percentage of PCs was significantly higher in patients with secondary DENV infection than in patients with primary infection (4.5% versus 1.0%; p=0.05). Viral RNA was detectable in 18 of 28 DENV infected patients with a highly variable viral load, but there was no correlation between viral load and percentage of PCs. We found an excellent correlation between percentage of PCs as assessed by morphology and by flow cytometry (r2= 0.85). The majority of CD138+ PCs (89%) had a shared immunophenotype (CD45+/CD19−/CD56−), which differed from normal plasmacells which are generally CD19+. In all cases the PCs were polyclonal. Conclusion: PB plasmacytosis, characterized by a transient presence of polyclonal PCs in the circulation, is a common event in DENV infection and is probably the result of a vigorous humoral immune response to dengue. With an increasing number of travelers to areas where dengue virus is endemic, it is important also for hematologists to recognize this benign cause of sometimes extreme plasmacytosis, for which no invasive procedures such as bone marrow examinations are needed. Disclosures: No relevant conflicts of interest to declare.

scholarly journals 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

2017 ◽  
Vol 56 (1) ◽  
Author(s):  
Nicole P. Lindsey ◽  
J. Erin Staples ◽  
Krista Powell ◽  
Ingrid B. Rabe ◽  
Marc Fischer ◽  
...  
Keyword(s):  
Puerto Rico ◽  
Virus Infection ◽  
Dengue Virus ◽  
Zika Virus ◽  
Denv Infection ◽  
The United States ◽  
American Samoa ◽  
Cross Reactivity ◽  
Immunoglobulin M ◽  
Positive Results

ABSTRACTCross-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.

scholarly journals Regulation of midgut cell proliferation impacts Aedes aegypti susceptibility to dengue virus

2018 ◽  
Author(s):  
Mabel L. Taracena ◽  
Vanessa Bottino-Rojas ◽  
Octavio A.C. Talyuli ◽  
Ana Beatriz Walter-Nuno ◽  
José Henrique M. Oliveira ◽  
...  
Keyword(s):  
Virus Infection ◽  
Aedes Aegypti ◽  
Dengue Virus ◽  
Denv Infection ◽  
Pathogen Transmission ◽  
Intestinal Lumen ◽  
Midgut Cell ◽  
Vector Borne Diseases ◽  
Cellular Processes ◽  
Vector Borne

AbstractAedes aegypti is the vector of some of the most important vector-borne diseases like Dengue, Chikungunya, Zika and Yellow fever, affecting millions of people worldwide. The cellular processes that follow a blood meal in the mosquito midgut are directly associated with pathogen transmission. We studied the homeostatic response of the midgut against oxidative stress, as well as bacterial and dengue virus (DENV) infections, focusing on the proliferative ability of the intestinal stem cells (ISC). Inhibition of the peritrophic matrix (PM) formation led to an increase in ROS production by the epithelial cells in response to contact with the resident microbiota, suggesting that maintenance of low levels of ROS in the intestinal lumen is key to keep ISCs division in balance. We show that dengue virus infection induces midgut cell division in both DENV susceptible (Rockefeller) and refractory (Orlando) mosquito strains. However, the susceptible strain delays the activation of the regeneration process compared with the refractory strain. Impairment of the Delta/Notch signaling, by silencing the Notch ligand Delta using RNAi, significantly increased the susceptibility of the refractory strains to DENV infection of the midgut. We propose that this cell replenishment is essential to control viral infection in the mosquito. Our study demonstrates that the intestinal epithelium of the blood fed mosquito is able to respond and defend against different challenges, including virus infection. In addition, we provide unprecedented evidence that the activation of a cellular regenerative program in the midgut is important for the determination of the mosquito vectorial competence.

scholarly journals Detection of Proteinuria by Colorimetric Method and Correlation with Disease Severity in Patients Dengue

2021 ◽  
Vol 27 (3) ◽  
pp. 244
Author(s):  
Acivrida Mega Charisma ◽  
Elis Anita Farida ◽  
Farida Anwari
Keyword(s):  
Virus Infection ◽  
Dengue Virus ◽  
Disease Severity ◽  
Dengue Infection ◽  
Urine Samples ◽  
P Value ◽  
Urine Protein ◽  
Dengue Virus Infection ◽  
Chi Square ◽  
Chi Square Test

Severe dengue virus infection often causes proteinuria through several mechanisms, such as leakage of plasma proteins caused by higher protein filtering in the kidneys. The condition of proteinuria in patients with dengue shock syndrome will affect the management, prognosis, and mortality of patients with dengue virus infection. The objectives of this study were to determine the presence of protein in urine samples in patients in which IgG/IgM dengue was detected, to determine the presence of protein in urine samples in patients without dengue infection, and to determine the relationship between proteinuria in dengue patients and the degree of disease severity. The study was conducted in March-June 2020 at the Clinical Laboratory and Inpatient Clinic of Vita Medika Kepung, Kediri Regency. The method used was the consecutive sampling technique. The minimum sample size was 100 respondents with criteria for suspected dengue infection, onset fever > 4 days, age > 2 years, and no indication of other infectious diseases (blood and urine), divided into two groups, group with positive dengue infection and non-dengue group. The results showed that proteinuria was detected in 26% of respondents, secondary dengue infection and positive serological test of IgG, IgM only IgG were detected in 24 (92.3%) respondents and positive IgG and IgM were found in 2 (7.7%) respondents, this was shown by the p-value = 0.000 in the Chi-Square test with a Prevalence Ratio (PR) value of 11,987. In addition, Chi-Square test results indicated that a higher urine protein/albumin led to more severe disease, with p-value = 0.012 and 0.025 (p <0.05) and PR values of 3.333 and 2.800. The results of this study concluded that there was a close relationship between high levels of protein/albumin in the urine with the degree of disease severity in patients with dengue infection. In addition, an increase in urine protein/albumin levels is always followed by a decrease in serum protein/albumin levels.

scholarly journals Studi in Silico Lima Senyawa Aktif Sebagai Penghambat Protein Virus Dengue

2019 ◽  
pp. 40-47
Author(s):  
Reni Herman
Keyword(s):  
Dengue Virus ◽  
In Silico ◽  
Dengue Infection ◽  
Epigallocatechin Gallate ◽  
Denv Infection ◽  
Virus Protein ◽  
Structural Protein ◽  
The Stability ◽  
The Tropics ◽  
Ns3 Protease

Dengue infection is an endemic disease in the tropics and subtropics, caused by dengue virus (DENV) infection. Some compounds have been shown to have antiviral effects on some viruses. In silico study is conducted to predict the stability of natural ingredient compounds: artemisinin, catechin, mangiferin, epigallocatechin gallate (EGCG), and quercetin in their interactions with dengue virus proteins at molecular level. This study is carried out using the 2008 version of the Molecular Operating Environment (MOE) software. Ligands are ribavirin as antiviral control whereas artemisinin, mangiferin, EGCG, and quercetin with 3D mole format structures. The downloaded DENV protein with PDB document format is the DENV serotype 2 envelope protein with 1OKE code, non structural protein 3 (NS3) with 2VBC code and NS5 protein with 1L9K code. In silico test generally showed that catechin, mangiferin, EGCG, and quercetin had more stable docking ligands to DENV’s proteins. In particular, mangiferin had stable docking ligand to envelope proteins, NS3 (helicase and protease) and in NS5-methyltransferase compared to ribavirin. Catechin stabled on NS3-protease, EGCG on NS3 (helicase and protease) and quercetin on NS3-protease. Artemisinin had less stabled bonds than ribavirin. The results indicated that catechin, mangiferin, EGCG, and quercetin had potential inhibition to DENV proteins whereas mangiferin was the most potential compound to inhibit dengue virus protein targets.

scholarly journals 1768. Dengue Virus Infection in Solid-Organ Transplant Recipients: Case Series and Literature Review

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S651-S652
Author(s):  
Fernando Rosso ◽  
Ana M Sanz ◽  
Luis Gabriel Parra-Lara ◽  
Pablo A Moncada ◽  
Juan D Vélez ◽  
...  
Keyword(s):  
Virus Infection ◽  
Literature Review ◽  
Dengue Virus ◽  
Dengue Infection ◽  
Organ Transplant ◽  
Case Series ◽  
Solid Organ Transplant ◽  
Severe Dengue ◽  
Solid Organ ◽  
Dengue Virus Infection

Abstract Background Dengue fever is the most prevalent arbovirus among humans, its incidence has increased since the re-emergence, and Colombia is a hyperendemic country for this infection. The number of solid-organ transplant (SOT) recipients, at risk of acquiring dengue virus infection, is constantly increasing, and there are few data regarding the clinical course and outcomes of dengue infection among this population. The aim of this study was to describe dengue virus infection in SOT recipients in Cali, Colombia. Methods We present a case series of SOT recipients with dengue virus infection, diagnosed by World Health Organization criteria and a positive NS1 and/or IgM dengue antibodies, which were attended at the FVL from 2001 to 2018. Furthermore, we performed a literature review regarding dengue infection in SOT recipients. Results A total of 20 patients were included: 17 kidney and 3 liver recipients. The median age was 50.5 years (IQR = 31–63.5), 65% were female. The median time from transplant to dengue was 27.6 months (IQR = 3.82–59.12), and 3 patients had the infection in the first month after the transplant. The most common symptoms were fever (95%), myalgia, headache, and abdominal pain. Warning signs were present in 75% of patients, thrombocytopenia and hemorrhagic manifestations were present in 30% and 15%, respectively. 35% of patients were classified as severe dengue, and 45% were managed at the intensive care unit. Regarding laboratory findings, six patients had transaminases elevation more than three times the upper limit and 7 had serum creatinine elevation, which returned to normal levels. All patients were discharged and none of them had alterations in the graft function. To date, there are approximately 180 reported cases of dengue in SOT recipients (Table 2). Conclusion Dengue represents a threat among SOT recipients. Unlike other reports, all patients in this series had a full recovery after the infection, suggesting that timely and effective management of patients and the access to high complexity services could prevent fatal cases. Disclosures All authors: No reported disclosures.

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