scholarly journals Micafungin Inhibits Dengue Virus Infection through the Disruption of Virus Binding, Entry, and Stability

2021 ◽  
Vol 14 (4) ◽  
pp. 338
Author(s):  
Yen-Chen Chen ◽  
Jeng-Wei Lu ◽  
Chia-Tsui Yeh ◽  
Te-Yu Lin ◽  
Feng-Cheng Liu ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Dengue Fever ◽  
Early Stage ◽  
Quantitative Polymerase Chain Reaction ◽  
Enterovirus 71 ◽  
Denv Infection ◽  
Immunofluorescence Assay ◽  
Dependent Manner ◽  
Virus Binding ◽  
Virus Serotype

Dengue fever is an arbovirus disease caused by infection with the dengue virus (DENV). Half of the world’s population lives under the threat of dengue fever, however, researchers have yet to develop any drugs that are clinically applicable to this infection. Micafungin is a member of the echinocandins family of anti-fungal drugs, capable of blocking the synthesis of β-1,3-D-glucan in the walls of fungal cells. Previous studies have demonstrated the effectiveness of Micafungin against infections of enterovirus 71 (EV71) and chikungunya virus (CHIKV). This is the first study demonstrating the effectiveness of micafungin in inhibiting the cytopathic effects of dengue virus serotype 2 (DENV-2) in a dose-dependent manner. Time-of-addition assays verified the inhibitory effects of micafungin in pre-treated, co-treated, and full-treatment groups. Binding and entry assays also demonstrated the effectiveness of micafungin in the early stage of DENV-2 infection. The virucidal efficacy of micafungin appears to lie in its ability to destroy the virion. Molecular docking assays revealed the binding of micafungin to the envelope protein of DENV-2, thereby revealing the mechanism by which micafungin affects the early stage of DENV infection and the stability of DENV. Two other micafungin analogs, caspofungin and anidulafungin, were also shown to have the antiviral effects on DENV-2. Finally, immunofluorescence assay (IFA) and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) confirmed the broad anti-DENV ability of micafungin against dengue virus serotypes 1, 3, and 4 (DENV-1, DENV-3, and DENV-4). Taken together, these results demonstrate the potential of micafungin and its analogs as candidates for the development of broad-spectrum treatments for DENV infection.

scholarly journals Retrograde Axonal Transport: a Major Transmission Route of Enterovirus 71 in Mice

2007 ◽  
Vol 81 (17) ◽  
pp. 8996-9003 ◽  
Author(s):  
Che-Szu Chen ◽  
Yi-Chuan Yao ◽  
Shin-Chao Lin ◽  
Yi-Ping Lee ◽  
Ya-Fang Wang ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Early Stage ◽  
Clinical Signs ◽  
Enterovirus 71 ◽  
Severe Infection ◽  
Dependent Manner ◽  
Transmission Route ◽  
Brain Infection ◽  
Reverse Pattern ◽  
Clinical Illness

ABSTRACT Inoculation of enterovirus 71 (EV71) by the oral (p.o.), intramuscular (i.m.), or intracranial route resulted in brain infection, flaccid paralysis, pulmonary dysfunction, and death of 7-day-old mice. The lag time of disease progression indicated that neuroinvasion from the inoculation sites was a prerequisite for the development of the clinical signs. Although EV71 p.o. inoculation led to a persistent viremia and a transient increase in blood-brain barrier permeability at the early stage of the infection, only low levels of virus, which led to neither severe infection nor clinical illness, could be detected in the brain, suggesting that hematogenous transport might not represent a major transmission route. In the spinal cord, following both p.o. and hind limb i.m. inoculation, the virus first appeared and increased rapidly in the lower segments, especially at the anterior horn areas, and then spread to the upper segments and brain in the presence of viremia. A reverse pattern, with the virus being first detected in the upper segment, was observed when the virus was i.m. inoculated in the forelimb. Colchicine, a fast axonal transport inhibitor, but not sciatic nerve transection reduced EV71 neuroinvasion in a dose-dependent manner, indicating a neuronal transmission of the virus.

scholarly journals Dengue Fever and Severe Dengue in Barbados, 2008–2016

2020 ◽  
Vol 5 (2) ◽  
pp. 68
Author(s):  
Kirk Osmond Douglas ◽  
Sudip Kumar Dutta ◽  
Byron Martina ◽  
Fatih Anfasa ◽  
T. Alafia Samuels ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Dengue Fever ◽  
Small Sample Size ◽  
Health Planning ◽  
Case Fatality ◽  
Small Sample ◽  
Severe Dengue ◽  
Medical Attention ◽  
Enzyme Linked Immunosorbent Assay ◽  
Virus Serotype

Analysis of the temporal, seasonal and demographic distribution of dengue virus (DENV) infections in Barbados was conducted using national surveillance data from a total of 3994 confirmed dengue cases. Diagnosis was confirmed either by DENV–specific real time reverse transcriptase polymerase chain reaction (rRT–PCR), or non–structural protein 1 (NS1) antigen or enzyme linked immunosorbent assay (ELISA) tests; a case fatality rate of 0.4% (10/3994) was observed. The dengue fever (DF) prevalence varied from 27.5 to 453.9 cases per 100,000 population among febrile patients who sought medical attention annually. DF cases occurred throughout the year with low level of transmission observed during the dry season (December to June), then increased transmission during rainy season (July to November) peaking in October. Three major dengue epidemics occurred in Barbados during 2010, 2013 and possibly 2016 with an emerging three–year interval. DF prevalence among febrile patients who sought medical attention overall was highest among the 10–19 years old age group. The highest DF hospitalisation prevalence was observed in 2013. Multiple serotypes circulated during the study period and Dengue virus serotype 2 (DENV–2) was the most prevalent serotype during 2010, whilst DENV–1 was the most prevalent serotype in 2013. Two DENV–1 strains from the 2013 DENV epidemic were genetically more closely related to South East Asian strains, than Caribbean or South American strains, and represent the first ever sequencing of DENV strains in Barbados. However, the small sample size (n = 2) limits any meaningful conclusions. DF prevalence was not significantly different between females and males. Public health planning should consider DENV inter–epidemic periodicity, the current COVID–19 pandemic and similar clinical symptomology between DF and COVID–19. The implementation of routine sequencing of DENV strains to obtain critical data can aid in battling DENV epidemics in Barbados.

scholarly journals Dengue virus infection in people residing in Africa: a systematic review and meta-analysis of prevalence studies

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Fredy Brice N. Simo ◽  
Jean Joel Bigna ◽  
Sebastien Kenmoe ◽  
Marie S. Ndangang ◽  
Elvis Temfack ◽  
...  
Keyword(s):  
Systematic Review ◽  
Dengue Virus ◽  
Dengue Fever ◽  
Meta Analysis ◽  
Denv Infection ◽  
Risk Of Bias ◽  
Prevalence Studies ◽  
Language Restriction ◽  
The Face ◽  
Apparently Healthy

Abstract Better knowledge of the face of the current dengue virus (DENV) epidemiology in Africa can help to implement efficient strategies to curb the burden of dengue fever. We conducted this systematic review and meta-analysis to determine the prevalence of DENV infection in Africa. We searched PubMed, EMBASE, African Journals Online, and Africa Index Medicus from January 1st, 2000 to June 10th, 2019 without any language restriction. We used a random-effects model to pool studies. A total of 76 studies (80,977 participants; 24 countries) were included. No study had high risk of bias. Twenty-two (29%) had moderate and 54 (71%) had low risk of bias. In apparently healthy individuals, the pooled prevalence of DENV was 15.6% (95% confidence interval 9.9–22.2), 3.5% (0.8–7.8), and 0.0% (0.0–0.5) respectively for immunoglobulins (Ig) G, IgM, and for ribonucleic acid (RNA) in apparently healthy populations. In populations presenting with fever, the prevalence was 24.8% (13.8–37.8), 10.8% (3.8–20.6k) and 8.4% (3.7–14.4) for IgG, IgM, and for RNA respectively. There was heterogeneity in the distribution between different regions of Africa. The prevalence of DENV infection is high in the African continent. Dengue fever therefore deserves more attention from healthcare workers, researchers, and health policy makers.

scholarly journals Development of a Dengue Virus Serotype-Specific Non-Structural Protein 1 Capture Immunochromatography Method

Sensors ◽  
2021 ◽  
Vol 21 (23) ◽  
pp. 7809
Author(s):  
Kanaporn Poltep ◽  
Emi E. Nakayama ◽  
Tadahiro Sasaki ◽  
Takeshi Kurosu ◽  
Yoshiki Takashima ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Pcr Amplification ◽  
Denv Infection ◽  
Epidemiologic Studies ◽  
Cross Reaction ◽  
Structural Protein ◽  
Current Standard ◽  
Denv Serotypes ◽  
Detection Systems ◽  
Virus Serotype

Four serotypes of dengue virus (DENV), type 1 to 4 (DENV-1 to DENV-4), exhibit approximately 25–40% of the difference in the encoded amino acid residues of viral proteins. Reverse transcription of RNA extracted from specimens followed by PCR amplification is the current standard method of DENV serotype determination. However, since this method is time-consuming, rapid detection systems are desirable. We established several mouse monoclonal antibodies directed against DENV non-structural protein 1 and integrated them into rapid DENV detection systems. We successfully developed serotype-specific immunochromatography systems for all four DENV serotypes. Each system can detect 104 copies/mL in 15 min using laboratory and clinical isolates of DENV. No cross-reaction between DENV serotypes was observed in these DENV isolates. We also confirmed that there was no cross-reaction with chikungunya, Japanese encephalitis, Sindbis, and Zika viruses. Evaluation of these systems using serum from DENV-infected individuals indicated a serotype specificity of almost 100%. These assay systems could accelerate both DENV infection diagnosis and epidemiologic studies in DENV-endemic areas.

scholarly journals Addition of Partial Envelope Domain II into Envelope Domain III of Dengue Virus Antigen Potentiates the Induction of Virus-Neutralizing Antibodies and Induces Protective Immunity

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 88 ◽  
Author(s):  
Jisang Park ◽  
Hyun-Young Lee ◽  
Ly Tuan Khai ◽  
Nguyen Thi Thu Thuy ◽  
Le Quynh Mai ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Dengue Fever ◽  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Secondary Infection ◽  
Febrile Illness ◽  
Hemorrhagic Fever ◽  
Denv Infection ◽  
Severe Dengue ◽  
Domain Iii

Dengue virus (DENV) comprises four serotypes in the family Flaviviridae and is a causative agent of dengue-related diseases, including dengue fever. Dengue fever is generally a self-limited febrile illness. However, secondary infection of patients with a suboptimal antibody (Ab) response provokes life-threatening severe dengue hemorrhagic fever or dengue shock syndrome. To develop a potent candidate subunit vaccine against DENV infection, we developed the EDII-cEDIII antigen, which contains partial envelope domain II (EDII) including the fusion loop and BC loop epitopes together with consensus envelope domain III (cEDIII) of all four serotypes of DENV. We purified Ab from mice after immunization with EDII-cEDIII or cEDIII and compared their virus neutralization and Ab-dependent enhancement of DENV infection. Anti-EDII-cEDIII Ab showed stronger neutralizing activity and lower Ab-dependent peak enhancement of DENV infection compared with anti-cEDIII Ab. Following injection of Ab-treated DENV into AG129 mice, anti-EDII-cEDIII Ab ameliorated DENV infection in tissues with primary and secondary infection more effectively than anti-cEDIII Ab. In addition, anti-EDII-cEDIII Ab protected against DENV1, 2, and 4 challenge. We conclude that EDII-cEDIII induces neutralizing and protective Abs, and thus, shows promise as a candidate subunit vaccine for DENV infection.

scholarly journals Receptor-activated human α2-macroglobulin interacts with the envelope protein of dengue virus and protects virions from temperature-induced inactivation through multivalent binding

2014 ◽  
Vol 95 (12) ◽  
pp. 2668-2676 ◽  
Author(s):  
Vivian Huerta ◽  
Patricia Toledo ◽  
Noralvis Fleitas ◽  
Alejandro Martín ◽  
Dianne Pupo ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Specific Binding ◽  
Interaction Network ◽  
Denv Infection ◽  
Virus Binding ◽  
Denv Serotypes ◽  
Α2 Macroglobulin ◽  
Multivalent Binding ◽  
Domain Iii ◽  
Amyloid P

Based on the hypothesis that interactions between virions and serum components may influence the outcome of dengue virus (DENV) infections, we decided to use affinity chromatography with domain III from the envelope (E) protein of DENV2 (DIIIE2) as a ligand to isolate virus-binding proteins from human plasma. This approach yielded serum amyloid P (SAP) and α2-macroglobulin (α2M) as novel viral interactors. After confirming the specific binding of both SAP and α2M to DIIIE2 by ELISA, the latter interaction was examined in greater detail. We obtain evidence suggesting that the binding species was actually the receptor-activated form of α2M (α2M*), that α2M* could bind monovalently to recombinant domain III from all four DENV serotypes with affinities in the micromolar range ranking as DENV4>DENV1~DENV2>DENV3 and that this interaction exhibited a strong avidity effect when multivalent binding was favoured (K D 8×10−8 M for DIIIE2). We also showed that α2M* bound to DENV virions of the four serotypes, protecting the virus from temperature-induced inactivation in the absence of serum and enhancing infectivity. The latter effect exhibited an ED50 of 2.9×10−8 M, also suggesting an avidity effect due to multivalent binding. These results will further contribute to the characterization of the virus–host factor interaction network during human DENV infection.

scholarly journals Ficus septicaplant extracts for treating Dengue virusin vitro

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3448 ◽  
Author(s):  
Nan-Chieh Huang ◽  
Wan-Ting Hung ◽  
Wei-Lun Tsai ◽  
Feng-Yi Lai ◽  
You-Sheng Lin ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Rna Viruses ◽  
Antiviral Drug ◽  
Denv Infection ◽  
Immunofluorescence Assay ◽  
Aichi Virus ◽  
Specific Therapy ◽  
Enveloped Virus ◽  
Positive Strand Rna

Dengue virus types 1-4 (DENV-1-4) are positive-strand RNA viruses with an envelope that belongs to theFlaviviridae. 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 plantsin vitro; immunofluorescence assay revealed that the methanol extracts of fruit, heartwood, leaves and stem fromFicus septicaBurm. f. had a promising anti-DENV-1 and DENV-2 effect. However, infection with the non-envelopepicornavirus, Aichi virus, was not inhibited by treatment withF. septicaextracts.F. septicamay be a candidate antiviral drug against an enveloped virus such as DENV.

scholarly journals Fatal and mild primary dengue virus infections imported to Norway from Africa and south-east Asia, 2008-2010

2010 ◽  
Vol 15 (38) ◽  
Author(s):  
K Vainio ◽  
S Noraas ◽  
M Holmberg ◽  
H Fremstad ◽  
M Wahlstrøm ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Dengue Fever ◽  
Fatal Case ◽  
Fatal Outcome ◽  
Dengue Shock Syndrome ◽  
Virus Infections ◽  
Virus Serotype ◽  
Serotype 1 ◽  
Type 3

Between 2008 and 2010, eight cases of viraemic dengue fever in travellers were diagnosed in Norway. They had returned from Eritrea, Thailand and Indonesia. All cases were primary dengue infections, seven non-complicated dengue fever and one dengue shock syndrome with a fatal outcome. Four patients were infected with dengue virus serotype 1, one with type 2 and three with type 3. Two cases from Thailand, the fatal case and the two imported from Eritrea were infected with type 1.

scholarly journals Mammalian animal models for dengue virus infection: a recent overview

2021 ◽  
Author(s):  
Mohammad Enamul Hoque Kayesh ◽  
Kyoko Tsukiyama-Kohara
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Dengue Virus ◽  
Dengue Fever ◽  
Vaccine Development ◽  
Wide Spectrum ◽  
Tree Shrew ◽  
Clinical Signs ◽  
Denv Infection ◽  
Health Concern

AbstractDengue, a rapidly spreading mosquito-borne human viral disease caused by dengue virus (DENV), is a public health concern in tropical and subtropical areas due to its expanding geographical range. DENV can cause a wide spectrum of illnesses in humans, ranging from asymptomatic infection or mild dengue fever (DF) to life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Dengue is caused by four DENV serotypes; however, dengue pathogenesis is complex and poorly understood. Establishing a useful animal model that can exhibit dengue-fever-like signs similar to those in humans is essential to improve our understanding of the host response and pathogenesis of DENV. Although several animal models, including mouse models, non-human primate models, and a recently reported tree shrew model, have been investigated for DENV infection, animal models with clinical signs that are similar to those of DF in humans have not yet been established. Although animal models are essential for understanding the pathogenesis of DENV infection and for drug and vaccine development, each animal model has its own strengths and limitations. Therefore, in this review, we provide a recent overview of animal models for DENV infection and pathogenesis, focusing on studies of the antibody-dependent enhancement (ADE) effect in animal models.

scholarly journals Dengue Virus Dysregulates Master Transcription Factors and PI3K/AKT/mTOR Signaling Pathway in Megakaryocytes

2021 ◽  
Vol 11 ◽  
Author(s):  
Anismrita Lahon ◽  
Ravi P. Arya ◽  
Akhil C. Banerjea
Keyword(s):  
Transcription Factors ◽  
Dengue Virus ◽  
Dengue Fever ◽  
Denv Infection ◽  
Mtor Pathway ◽  
Mtor Signaling Pathway ◽  
Low Platelet Count ◽  
Pharmacologic Inhibition ◽  
Specific Inhibitors

Dengue virus (DENV) infection can cause either self-limited dengue fever or hemorrhagic complications. Low platelet count is one of the manifestations of dengue fever. Megakaryocytes are the sole producers of platelets. However, the role of both host and viral factors in megakaryocyte development, maturation, and platelet production is largely unknown in DENV infection. PI3K/AKT/mTOR pathway plays a significant role in cell survival, maturation, and megakaryocyte development. We were interested to check whether pathogenic insult can impact this pathway. We observed decreased expression of most of the major key molecules associated with the PI3K/AKT/mTOR pathway in DENV infected MEG-01 cells. In this study, the involvement of PI3K/AKT/mTOR pathway in megakaryocyte development and maturation was confirmed with the use of specific inhibitors in infected MEG-01 cells. Our results showed that direct pharmacologic inhibition of this pathway greatly impacted megakaryopoiesis associated molecule CD61 and some essential transcription factors (GATA-1, GATA-2, and NF-E2). Additionally, we observed apoptosis in megakaryocytes due to DENV infection. Our results may suggest that DENV impairs PI3K/AKT/mTOR axis and molecules involved in the development and maturation of megakaryocytes. It is imperative to investigate the role of these molecules in the context of megakaryopoiesis during DENV infection to better understand the pathways and mechanisms, which in turn might provide insights into the development of antiviral strategies.

Sign in / Sign up

Export Citation Format

Share Document