Genomic Basis of Dengue Virus: Drawing the Puzzle of Dengue Viral Infection

2016 ◽  
Vol 2 (2) ◽  
pp. 16
Author(s):  
Afeefa Kiran Ch
Author(s):  
Samir Casseb ◽  
Karla de Melo

Dengue is an acute febrile disease caused by a virus of the genus Flavivirus, family Flaviviridae, endemic in tropical regions of the globe. The agent is a virus with single-stranded RNA, classified into four distinct dengue virus (DENV) serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. The host’s innate and adaptive immune responses play an essential role in determining the natural history of viral infections, especially in dengue. In this context, it has observed in recent years that the presence of RNA interference (RNAi) in viral infection processes is increasing, as well as immune defense. The context microRNAs (miRNAs) go for stood out, as their presence during viral infection, both in the replication of the virus and in the defense against these infections, becomes increasingly noticeable, therefore, making it increasingly necessary to better understand the role of these small RNAs within viral infection by DENV and what their consequences are in aggravating the consequences of patients affected by this disease.


PeerJ ◽  
2018 ◽  
Vol 5 ◽  
pp. e3939 ◽  
Author(s):  
Wei-Lian Tan ◽  
Yean Kee Lee ◽  
Yen Fong Ho ◽  
Rohana Yusof ◽  
Noorsaadah Abdul Rahman ◽  
...  

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.


Virology ◽  
2010 ◽  
Vol 396 (1) ◽  
pp. 30-36 ◽  
Author(s):  
Ivonne Ceballos-Olvera ◽  
Salvador Chávez-Salinas ◽  
Fernando Medina ◽  
Juan E. Ludert ◽  
Rosa M. del Angel

2015 ◽  
Vol 3 (2) ◽  
Author(s):  
Ellisabeth M. Harahap ◽  
Arthur E. Mongan ◽  
Maya F. Memah

Abstract: Dengue is the most rapidly spreading mosquito-borne viral disease in the world. The decreasing leukocytes can be found between the third and eighth day with normal differential telling. The number of granulocytes decreases on the third until the eighth day. This study used a cross-sectional design. esearch. Samples were children with dengue virus infection at Wolter Mongisidi Hospital, Advent Hospital, and Pancaran Kasih Hospital in Manado from December 2014 until January 2015. There were 36 children as samples. The results showed that 48.6% of samples had increases of basophils, 54% had decreases of eosinophils, 64.8% had decreases of neutrophils, 54% had increases of lymphocytes, and 59.4% had increases of monocytes. Conclusion: In this study, most of the children with dengue viral infection had decreased number of neutrophil.Keywords: dengue viral infection, children, differential count, leukocyteAbstrak: Infeksi virus dengue adalah penyakit virus ditularkan oleh nyamuk dengan penyebaran paling cepat di dunia. Penurunan leukosit dapat dijumpai antara hari ke 1-3 demam dengan hitung jenis yang masih dalam batas normal. Jumlah granulosit menurun pada hari ke 3-8. Penelitian ini bertujuan untuk mengetahui hitung jenis leukosit pada anak terinfeksi virus dengue di Manado. bersifat potong lintang. Penelitian ini menggunakan desain potong lintang. Sampel penelitian ialah pasien anak yang terinfeksi virus dengue di RS Wolter Mongisidi Manado, RS Advent Manado, dan RS Pancaran Kasih Manado selama bulan Desember 2014 sampai Januari 2015. Jumlah sampel sebanyak 36 anak. Hasil penelitian menunjukkan 48,6% sampel mengalami peningkatan jumlah basofil, 54% penurunan eosinofil, 64,8% penurunan neutrofil, 54% peningkatan limfosit, dan 59,4% peningkatan monosit. Simpulan: Pada penelitian ini sebagian besar pasien anak terinfeksi virus dengue menunjukkan penurunan neutrofil.Kata kunci: infeksi virus dengue, anak, hitung jenis, leukosit


2018 ◽  
Vol 7 (1) ◽  
pp. 21
Author(s):  
Soegeng Soegijanto ◽  
Sufiandika Nuryandari ◽  
Siti Churrotin ◽  
Teguh Hari Sucipto

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 gain new prevention method before the occurrence of outbreak.


Author(s):  
Alok Kumar Moharana ◽  
Rudra Narayan Dash ◽  
Bharat Bhusan Subudhi

: The challenges of viral infection have increased in recent decades due to the emergence of resistance, crossresistance and drying up of antiviral drug discovery. Many neglected tropical viruses including the chikungunya virus, dengue virus & Japanese encephalitis virus have gradually become global pathogens. This has further increased the burden of viral infection which necessitates the continuous development of antiviral therapy. The antiviral chemistry began with the development of thiosemicarbazide derived thiosemicarbazones as antiviral. Although very few thiosemicarbazides have progressed into clinical application, it still inspires antiviral development. During last 3 decades (1990-2020), several efforts have been made to develop suitable antiviral by using thiosemicarbazide scaffold. Its hybridization with other pharmacophores has been used as a strategy to enhance safety and efficacy. Cyclization and substitution of thiosemicarbazides have also been used to develop potent antiviral. With the ability to form coordinate bonds, thiosemicarbazides have been used either as metal complex or chelator against viruses. This work is an attempt to systematically review the research on the use of thiosemicarbazides as an antiviral scaffold. It also reviews the structureactivity relationship and translational suitability of thiosemicarbazide derived compounds.


mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
David L. Lin ◽  
Natalia A. Cherepanova ◽  
Leonia Bozzacco ◽  
Margaret R. MacDonald ◽  
Reid Gilmore ◽  
...  

ABSTRACT Dengue virus (DENV) is the most common arboviral infection globally, infecting an estimated 390 million people each year. We employed a genome-wide clustered regularly interspaced short palindromic repeat (CRISPR) screen to identify host dependency factors required for DENV propagation and identified the oligosaccharyltransferase (OST) complex as an essential host factor for DENV infection. Mammalian cells express two OSTs containing either STT3A or STT3B. We found that the canonical catalytic function of the OSTs as oligosaccharyltransferases is not necessary for DENV infection, as cells expressing catalytically inactive STT3A or STT3B are able to support DENV propagation. However, the OST subunit MAGT1, which associates with STT3B, is also required for DENV propagation. MAGT1 expression requires STT3B, and a catalytically inactive STT3B also rescues MAGT1 expression, supporting the hypothesis that STT3B serves to stabilize MAGT1 in the context of DENV infection. We found that the oxidoreductase CXXC active site motif of MAGT1 was necessary for DENV propagation, as cells expressing an AXXA MAGT1 mutant were unable to support DENV infection. Interestingly, cells expressing single-cysteine CXXA or AXXC mutants of MAGT1 were able to support DENV propagation. Utilizing the engineered peroxidase APEX2, we demonstrate the close proximity between MAGT1 and NS1 or NS4B during DENV infection. These results reveal that the oxidoreductase activity of the STT3B-containing OST is necessary for DENV infection, which may guide the development of antiviral agents targeting DENV. IMPORTANCE The host oligosaccharyltransferase (OST) complexes have been identified as essential host factors for dengue virus (DENV) replication; however, their functions during DENV infection are unclear. A previous study showed that the canonical OST activity was dispensable for DENV replication, suggesting that the OST complexes serve as scaffolds for DENV replication. However, our work demonstrates that one function of the OST complex during DENV infection is to provide oxidoreductase activity via the OST subunit MAGT1. We also show that MAGT1 associates with DENV NS1 and NS4B during viral infection, suggesting that these nonstructural proteins may be targets of MAGT1 oxidoreductase activity. These results provide insight into the cell biology of DENV infection, which may guide the development of antivirals against DENV. IMPORTANCE The host oligosaccharyltransferase (OST) complexes have been identified as essential host factors for dengue virus (DENV) replication; however, their functions during DENV infection are unclear. A previous study showed that the canonical OST activity was dispensable for DENV replication, suggesting that the OST complexes serve as scaffolds for DENV replication. However, our work demonstrates that one function of the OST complex during DENV infection is to provide oxidoreductase activity via the OST subunit MAGT1. We also show that MAGT1 associates with DENV NS1 and NS4B during viral infection, suggesting that these nonstructural proteins may be targets of MAGT1 oxidoreductase activity. These results provide insight into the cell biology of DENV infection, which may guide the development of antivirals against DENV.


Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 395
Author(s):  
Chih-Chieh Cheng ◽  
Eny Sofiyatun ◽  
Wei-June Chen ◽  
Lian-Chen Wang

Dengue fever is a mosquito-borne viral disease of increasing global importance. The disease has caused heavy burdens due to frequent outbreaks in tropical and subtropical areas of the world. The dengue virus (DENV) is generally transmitted between human hosts via the bite of a mosquito vector, primarily Aedes aegypti and Ae. albopictus as a minor species. It is known that the virus needs to alternately infect mosquito and human cells. DENV-induced cell death is relevant to the pathogenesis in humans as infected cells undergo apoptosis. In contrast, mosquito cells mostly survive the infection; this allows infected mosquitoes to remain healthy enough to serve as an efficient vector in nature. Overexpression of antioxidant genes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutaredoxin (Grx), thioredoxin (Trx), and protein disulfide isomerase (PDI) have been detected in DENV2-infected mosquito cells. Additional antioxidants, including GST, eukaryotic translation initiation factor 5A (eIF5a), and p53 isoform 2 (p53-2), and perhaps some others, are also involved in creating an intracellular environment suitable for cell replication and viral infection. Antiapoptotic effects involving inhibitor of apoptosis (IAP) upregulation and subsequent elevation of caspase-9 and caspase-3 activities also play crucial roles in the ability of mosquito cells to survive DENV infection. This article focused on the effects of intracellular responses in mosquito cells to infection primarily by DENVs. It may provide more information to better understand virus/cell interactions that can possibly elucidate the evolutionary pathway that led to the mosquito becoming a vector.


Author(s):  
Kavithambigai Ellan ◽  
Ravindran Thayan ◽  
Jegadeesh Raman ◽  
Kazuya I. P. J. Hidari ◽  
Norizah Ismail ◽  
...  

Abstract Background Dengue is a mosquito-borne viral infection that has become a major public health concern worldwide. Presently, there is no specific vaccine or treatment available for dengue viral infection. Methods Lignosus rhinocerotis, Pleurotus giganteus, Hericium erinaceus, Schizophyllum commune and Ganoderma lucidium were selected for evaluation of their in-vitro anti-dengue virus serotype 2 (DENV-2) activities. Hot aqueous extracts (HAEs), ethanol extracts (EEs), hexane soluble extracts (HSEs), ethyl acetate soluble extracts (ESEs) and aqueous soluble extracts (ASEs) were prepared from the selected mushrooms. The cytotoxic effects of the extracts were evaluated by the MTT assay. The anti-DENV-2 activities of the extracts were evaluated in three different assays: simultaneous, attachment and penetration assays were perfomed using plaque reduction assays and RT-qPCR assays. The effect of the addition time on viral replication was assessed by the time of addition assay, and a virucidal assay was carried out to evaluate the direct effect of each mushroom extract on DENV-2. The chemical composition of glucans, and the protein and phenolic acid contents in the extracts were estimated. Results We found that the HAEs and ASEs of L. rhinocerotis, P. giganteus, H. erinaceus and S. commune were the least toxic to Vero cells and showed very prominent anti-DENV2 activity. The 50% inhibitory concentration (IC50) values of the ASEs ranged between 399.2–637.9 μg/ml, while for the HAEs the range was 312.9–680.6 μg/ml during simultaneous treatment. Significant anti-dengue activity was also detected in the penetration assay of ASEs (IC50: 226.3–315.4 μg/ml) and HAEs (IC50: 943.1–2080.2 μg/ml). Similarly, we observed a marked reduction in the expression levels of the ENV and NS5 genes in the simultaneous and penetration assays of the ASEs and HAEs. Time-of-addition experiments showed that the highest percent of anti-DENV2 activity was observed when the mushroom extracts were added immediately after virus adsorption. None of the extracts exhibited virucidal effect. Chemical composition analysis showed that the major components in the mushroom HAEs and ASEs were glucan (beta D-glucan) and proteins, however, there was no significant correlation between the anti-dengue activity and the concentration of glucans and proteins. Conclusion These findings demonstrated the potential of mushroom extracts as anti-dengue therapeutic agents with less toxic effects.


2016 ◽  
Vol 18 (44) ◽  
pp. 30288-30296 ◽  
Author(s):  
M. C. P. Lima ◽  
G. M. Seabra

The dengue virus (DENV) is the causative agent of the viral infection dengue fever. It utilizes the NS2B-NS3pro serine protease to cleave the viral polyprotein into its constituents. We present here a QM/MM to study of the first step (acylation) of the reaction catalyzed by NS2B-NS3pro, using PDDG/PM3 for the QM subsystem, and Amber ff99SB for the MM subsystem.


Sign in / Sign up

Export Citation Format

Share Document