A Non Mouse-Adapted Dengue Virus Strain as a New Model of Severe Dengue Infection in AG129 Mice

Dengue virus is a mosquito borne Flavivirus and the most prevalent arbovirus in tropical and subtropical regions around the world. The incidence of dengue has increased drastically over the last few years at an alarming rate. The clinical manifestation of dengue ranges from asymptomatic infection to severe dengue. Even though the viral kinetics of dengue infection is lacking, innate immune response and humoral immune response are thought to play a major role in controlling the virus count. Here, we developed a computer simulation mathematical model including both innate and adaptive immune responses to study the within-host dynamics of dengue virus infection. A sensitivity analysis was carried out to identify key parameters that would contribute towards severe dengue. A detailed stability analysis was carried out to identify relevant range of parameters that contributes to different outcomes of the infection. This study provides a qualitative understanding of the biological factors that can explain the viral kinetics during a dengue infection.

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Retrospective meta-transcriptomic identification of severe dengue in a traveller returning from Africa to Sweden, 1990

10.1101/2020.09.08.20184580 ◽

2020 ◽

Author(s):

Kristian Alfsnes ◽

Nina Lagerqvist ◽

Sirkka Vene ◽

Jon Bohlin ◽

Jenny Verner-Carlsson ◽

...

Keyword(s):

Dengue Virus ◽

Rna Sequencing ◽

Dengue Infection ◽

Severe Dengue ◽

Diagnostic Study ◽

Aetiological Agent ◽

Haemorrhagic Fever ◽

Imported Case ◽

Plasma And Urine Samples ◽

Retrospective Investigation

The first imported case of severe haemorrhagic fever in Sweden was reported in 1990. Despite extensive diagnostic study, no aetiological agent was identified. Following retrospective investigation with total RNA-sequencing of plasma and urine samples collected during between 7 to 36 days from onset of symptoms, we identified dengue virus 3 (DENV-3) and a human pegivirus (HPgV). We conclude that the patient most likely suffered from haemorrhagic symptoms due to a severe dengue infection.

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1631 ◽

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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Dengue Fever: Clinical, Laboratory Profile and Outcome in Pediatric Patient

International Journal of Medical Science and Diagnosis Research ◽

10.32553/ijmsdr.v6i1.892 ◽

2022 ◽

Vol 6 (1) ◽

Author(s):

Pooja Gandhi ◽

Pinkal Taral ◽

Krunal Patel ◽

Sanketsinh Rathod ◽

Bhavini Rathwa

Keyword(s):

Platelet Count ◽

Dengue Virus ◽

Dengue Fever ◽

Care Center ◽

Dengue Infection ◽

Tertiary Care ◽

Clinical Profile ◽

Severe Dengue ◽

Diverse Range ◽

Laboratory Profile

Introduction: Infection with any of the 4 dengue virus serotypes results in a diverse range of symptoms, from mild undifferentiated fever to life-threatening hemorrhagic fever and shock. Given that dengue virus infection elicits such a broad range of clinical symptoms, early and accurate laboratory diagnosis is essential for appropriate patient management. So a study was carried out to know its clinical profile, correlation between the laboratory profile and the severity of dengue fever and outcome in dengue patients. Aim: To study the clinical profile, correlation between the laboratory profile and the severity of dengue fever and outcome in dengue patients at tertiary care center. Method: Retrospective Observational study from 1st May 2019 to 31st April 2021. Result: Total 323 patients were studied during 1st May 2019 to 31st April 2021. Most common presentation was fever (100%), most common clinical finding is hepatomegaly (14.2%). All severe dengue infection has platelet count < 50000/cumm. In study of 323 patients 194(60%) of dengue fever,85(26.4%) of DHF GRADE 1,9(2.8%) of DHF GRADE 2 were discharged .13(4%) patients of DSS were expired.22 patients (6.8%) went DAMA. Conclusion: Reliable diagnosis of dengue fever in endemic areas can be done by clinical parameters like presence of nausea, vomiting, pain abdomen and hepatomegaly. Monitoring platelet count, hematocrit and WBC count is very useful for management of dengue cases. Keywords: dengue fever, platelet count, outcome

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Discovery of Dengue Virus Inhibitors

Current Medicinal Chemistry ◽

10.2174/0929867326666181204155336 ◽

2020 ◽

Vol 27 (30) ◽

pp. 4945-5036 ◽

Cited By ~ 1

Author(s):

Adib Afandi Abdullah ◽

Yean Kee Lee ◽

Sek Peng Chin ◽

See Khai Lim ◽

Vannajan Sanghiran Lee ◽

...

Keyword(s):

Dengue Virus ◽

Drug Targets ◽

Protective Efficacy ◽

Dengue Infection ◽

Viral Proteins ◽

Host Factors ◽

Structural Proteins ◽

Severe Dengue ◽

Dengue Vaccine

To date, there is still no approved anti-dengue agent to treat dengue infection in the market. Although the only licensed dengue vaccine, Dengvaxia is available, its protective efficacy against serotypes 1 and 2 of dengue virus was reported to be lower than serotypes 3 and 4. Moreover, according to WHO, the risk of being hospitalized and having severe dengue increased in seronegative individuals after they received Dengvaxia vaccination. Nevertheless, various studies had been carried out in search of dengue virus inhibitors. These studies focused on the structural (C, prM, E) and non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) of dengue virus as well as host factors as drug targets. Hence, this article provides an overall up-to-date review of the discovery of dengue virus inhibitors that are only targeting the structural and non-structural viral proteins as drug targets.

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High Expression of FcγII (CD32) Receptor on Monocytes in Dengue Infected Patients

The Indonesian Biomedical Journal ◽

10.18585/inabj.v10i3.434 ◽

2018 ◽

Vol 10 (3) ◽

pp. 256-62

Author(s):

Umi Solekhah Intansari ◽

Harina Salim ◽

Usi Sukorini ◽

Adika Zhulhi Arjana ◽

Muhammad Juffrie

Keyword(s):

Flow Cytometry ◽

Dengue Virus ◽

Healthy Subjects ◽

Dengue Infection ◽

Absolute Number ◽

Severe Dengue ◽

Cross Sectional ◽

Fluorescent Intensity ◽

The Mean ◽

Cross Sectional Design

BACKGROUND: Pathogenesis of severe dengue infection has not been elucidated. Immune complex of pre-existing antibodies and heterotypic dengue virus bind to FcγII (cluster of differentiation (CD32)) receptor (FcγIIR) on monocyte facilitates entry and replication of dengue virus. Aim of this study was to evaluate the expression of FcγIIR on monocytes in patients infected with dengue and in healthy subjects.METHODS: This study used a cross-sectional design that included patients infected with dengue who were hospitalized in Dr. Sardjito General Hospital, Panembahan Senopati Hospital, and Sleman Hospital, who met the inclusion criteria and selected consecutively. Examinations were completed using a lyse, no-wash method of flow cytometry. Computerized statistical analysis was conducted and was considered to be significant if p<0.05.RESULTS: Sixty-five study subjects were divided into healthy subjects (24 subjects) and patients with dengue infection (41 subjects). There were no significant differences in hemoglobin (Hb) and hematocrit (Hct) values between the groups, but differences were found in the number of leukocytes, absolute number of monocytes and platelet count (p<0.001, 0.002 and <0.001, respectively). The mean expression of FcγIIR monocytes in patients with dengue infection (208.77±32.06 median fluorescent intensity (MFI)) and the healthy subjects (124.03±47.76 MFI) with p<0.0001.CONCLUSION: The mean expression of FcγIIR monocytes in patients with dengue infection was higher than in healthy subjects.KEYWORDS: dengue infection, FcγII (CD32) receptor monocyte, flow cytometry

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Karakteristik Klinis dan Virologis Penderita Demam Berdarah Dengue di Kota Bandar Lampung

ASPIRATOR - Journal of Vector-borne Disease Studies ◽

10.22435/asp.v12i2.3095 ◽

2020 ◽

Vol 12 (2) ◽

pp. 85-92

Author(s):

Nurminha Nurminha ◽

Tori Rihiantoro ◽

Mara Ipa

Keyword(s):

Dengue Virus ◽

Clinical Symptoms ◽

Serological Test ◽

Secondary Infection ◽

Dengue Infection ◽

Clinical Manifestations ◽

Denv Infection ◽

Severe Dengue ◽

Virus Serotype ◽

Degree Of Severity

Abstract. Clinical symptoms of dengue virus (DENV) infection range from asymptomatic mild dengue fever(DF), more severe dengue hemorrhagic fever (DHF) up to dengue shock syndrome. One of the determinantsof dengue infection severity was virus virulence. This study aimed to determine the clinical and virologicalcharacteristics of dengue virus infection patients based on the severity degree. A cross-sectional study wasconducted in RSUD Dr. H. Abdul Moeloek, Lampung Province between July-November 2016 with 56 denguepatients as samples selected using purposive sampling. The serological test was done using a rapiddiagnostic test. Blood samples for DENV serotype identification were examined using reverse-transcriptionpolymerase chain reaction. Classification of DENV infection severity was obtained from the patient’s medicalrecord. The results showed that the most common clinical manifestations were fever, headache, and retroorbitalpain, appearing in all patients from every degree of severity. There were Grade I DHF patients whoexperienced Myalgia (15.6%) and petechiae (22.2%). Laboratory results showed that thrombocytopeniaappeared in every grade, even though 13.3% of grade I patients did not experience it. Secondary infectionwas found in 92.9% of samples, and all DENV serotype can be detected in 39.2%samples: DENV-1 (46.7%),DENV-2 (6.7%), DENV-3 (26.7%), and DENV-4 (20%). This study concluded that the majority of clinicalcharacteristics in DHF patients are in line with the degree of severity, with the bleeding as the dominantmanifestation in patients with grade II-IV. Virological characteristics of DENV-1 are dominant in all patientswith DHF grade I-IV.Keywords: dengue virus, serotype, severity, secondary infection, Bandar Lampung

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Dengue virus infection elicits highly polarized CX3CR1+cytotoxic CD4+T cells associated with protective immunity

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1505956112 ◽

2015 ◽

Vol 112 (31) ◽

pp. E4256-E4263 ◽

Cited By ~ 139

Author(s):

Daniela Weiskopf ◽

Derek J. Bangs ◽

John Sidney ◽

Ravi V. Kolla ◽

Aruna D. De Silva ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Dengue Virus ◽

Ex Vivo ◽

Natural Infection ◽

Dengue Infection ◽

Flow Cytometric Analysis ◽

T Cell Responses ◽

Severe Dengue ◽

Cell Responses

Dengue virus (DENV) is a rapidly spreading pathogen with unusual pathogenesis, and correlates of protection from severe dengue disease and vaccine efficacy have not yet been established. Although DENV-specific CD8+T-cell responses have been extensively studied, the breadth and specificity of CD4+T-cell responses remains to be defined. Here we define HLA-restricted CD4+T-cell epitopes resulting from natural infection with dengue virus in a hyperepidemic setting. Ex vivo flow-cytometric analysis of DENV-specific CD4+T cells revealed that the virus-specific cells were highly polarized, with a strong bias toward a CX3CR1+Eomesodermin+perforin+granzyme B+CD45RA+CD4 CTL phenotype. Importantly, these cells correlated with a protective HLA DR allele, and we demonstrate that these cells have direct ex vivo DENV-specific cytolytic activity. We speculate that cytotoxic dengue-specific CD4+T cells may play a role in the control of dengue infection in vivo, and this immune correlate may be a key target for dengue virus vaccine development.

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The Role of Autophagy-Mediated Dengue Virus Antibody-Dependent Enhancement Infection of THP-1 Cells

Intervirology ◽

10.1159/000511420 ◽

2020 ◽

Vol 63 (1-6) ◽

pp. 57-65

Author(s):

Liming Jiang ◽

Qiangming Sun

Keyword(s):

Dengue Virus ◽

Dengue Infection ◽

Denv Infection ◽

Inhibitory Effect ◽

Severe Dengue ◽

Heat Map ◽

Antibody Dependent Enhancement ◽

Transmission Electron ◽

Underlying Mechanisms

Background: Antibody-dependent enhancement (ADE) of dengue virus (DENV) infection is identified as the main risk factor of severe dengue diseases. The underlying mechanisms leading to severe dengue fever remain unclear. Methods: THP-1 cells were treated with an autophagy inducer (rapamycin) or inhibitor (3-methyladenine [3-MA]) and infected with DENV and DENV-ADE. In order to investigate the expression profile of autophagy-related genes in DENV-ADE and DENV direct infection of THP-1 cells, the PCR array including 84 autophagy-related genes was selected to detect the expression of related genes, and then heat map and clustergram were established by analysis software to compare the expression differences of these genes between the DENV-ADE and DENV direct infection. Results: Autophagy-inducing complex related genes ATG5 and ATG12 were upregulated, and autophagosomes were also observed by transmission electron microscopy among DENV-ADE- and DENV-infected THP-1 cells, which indicated that autophagy was involved in dengue infection. The results show that 3-MA has a significant inhibitory effect on ATG12 in THP-1 cells; on the contrary, the expression of ATG12 was upregulated in THP-1 cells that were treated with rapamycin. The autophagy-related genes ESR1, INS, BNIP3, FAS, TGM2, ATG9B, and DAPK1 exhibited significant differences between DENV-ADE and DENV direct infection groups. Conclusion: In the present study, an additional mechanism of autophagy was inhibited by the autophagy inhibitor (3-MA) in DENV- and DENV-ADE-infected THP-1 cells. Our finding provided a clear link between autophagy and antibody-enhanced infection of DENV.

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