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";s:4:"text";s:21964:"Interferons exert diverse antiviral functions against viral replication, which can activate interferon-stimulated genes and related mechanisms. Wang WK, Chao DY, Kao CL, Wu HC, Liu YC, Li CM, Lin SC, Ho ST, Huang JH, King CC. 2002;108(5):717–25. Dengue is a major public health concern in the tropical and sub-tropical world with no effective treatment. CAS  Halstead SB. Total binding (100%) corresponds to the sera binding in the absence of ammonium thiocyanate. 2006;193(8):1078–88. HPA-1 is synthesized as a 65-kDa non-active precursor that subsequently undergoes proteolytic cleavage to yield 8-kDa and 50-kDa subunits that heterodimerize to form an active enzyme. Keywords: dengue virus, non-structural protein-1, NS1, phage display, monoclonal antibody, human single-chain variable fragment antibody, HuScFv Introduction Dengue virus (DENV) is the etiologic agent of dengue fever (DF) in humans, which is an important public health problem. Antivir Res. The It exists as four antigenically different serotypes that are further classified into genotypes with varying degrees of pathogenicity. 2018;14(4):e1007033. Protein names i: Submitted name: Non-structural protein 1 Imported. This site needs JavaScript to work properly. Article A Non-structural 1 Protein G53D Substitution Attenuates a Clinically Tested Live Dengue Vaccine Milly M. Choy,1,6 Dorothy H.L. Therefore, minocycline may modulate both virus replication and the host immune response. J Biomed Sci 25, 58 (2018). Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Dengue virus non-structural Protein-1 expression and associated risk factors among febrile Patients attending University of Abuja Teaching Hospital, Nigeria. When we tested the induction of cellular immune responses, the number of IFN-γ producing cells was higher in αDEC-NS1 immunized animals. Antibody-dependent enhancement of dengue virus growth in human monocytes as a risk factor for dengue hemorrhagic fever. Only when we better understand the molecular mechanisms of DENV pathogenesis can a more effective and specific therapy or vaccine against DHF/DSS be developed. 2020 Oct 14;19:240-252. doi: 10.1016/j.omto.2020.10.007. However, due to the limited understanding of dengue pathogenesis, no satisfactory therapies to treat nor vaccine to prevent dengue infection are available, and the mortality of DHF/DSS is still high. J Gen Virol. Circulating cytokines and chemokines associated with plasma leakage and hepatic dysfunction in Brazilian children with dengue fever. Therefore, the vaccination of seronegative individuals with Dengvaxia may enhance dengue disease severity but not protection due to ADE [104]. NS1 antigen (Ag) circulates uniformly in all serotypes of DENV and it circulates at high level during the first few days of illness. H-R.C. In addition, mice immunized with the αDEC-NS1 mAb were significantly protected from a lethal intracranial challenge with the DENV2 NGC strain when compared to mice immunized with αDCIR2-NS1 mAb. Google Scholar. This site needs JavaScript to work properly. 1989;40(41):444–51. https://doi.org/10.1186/s12929-018-0462-0, DOI: https://doi.org/10.1186/s12929-018-0462-0. Based on ADE, antibodies that are generated by a single DENV infection contribute to lasting homotypic immunity but may permit heterotypic DENV infection. The numbers indicate the same order as in (A). J Infect Dis. Savidis G, McDougall WM, Meraner P, Perreira JM, Portmann JM, Trincucci G, John SP, Aker AM, Renzette N, Robbins DR, et al. PubMed  Journal of Biomedical Science Activated HPA-1 enhances shedding of the transmembrane heparan sulfate proteoglycan syndecan-1 (CD138) and elevates the CD138 level in the bloodstream [57, 58]. eCollection 2021 Jul. Avirutnan P, Zhang L, Punyadee N, Manuyakorn A, Puttikhunt C, Kasinrerk W, Malasit P, Atkinson JP, Diamond MS. Secreted NS1 of dengue virus attaches to the surface of cells via interactions with heparan sulfate and chondroitin sulfate E. PLoS Pathog. Lin CF, Chiu SC, Hsiao YL, Wan SW, Lei HY, Shiau AL, Liu HS, Yeh TM, Chen SH, Liu CC, et al. 2012;30(5):837–45. PubMed Central  However, another study demonstrated that NS1-activated TNF-α and IL-1β mRNA expression and IL-6 secretion were attenuated by blocking TLR4 in PBMCs [40]. diagnosis, treatment, prevention and control. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. 2014;6(2):683–708. volume 25, Article number: 58 (2018) Dengue haemorrhagic fever. This book investigates how this facilitates the design and development of potent antiviral agents used against life-threatening viruses. Modhiran N, Watterson D, Muller DA, Panetta AK, Sester DP, Liu L, Hume DA, Stacey KJ, Young PR. [1-5] The other 7 non-structural (NS) proteins are NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5. NCI CPTC Antibody Characterization Program. An effective drug against DENV infection is in great demand until a satisfactory vaccine becomes available. 2015;520(7545):109–13. J Thromb Haemost. P-value indicators * and *** refer to p<0.05 and p<0.01, respectively, while ns = not significant. Chan,1 Menchie Manuel,1 R. Manjunatha Kini,3 Kuan Rong Chan,1 Subhash G. Vasudevan,1,5 and Eng Eong Ooi1,4,5,7,* 2015;149:138–47. Evaluation of protective efficacy and immune mechanisms of using a non-structural protein NS1 in DNA vaccine against dengue 2 virus in mice. Kliks SC, Nimmanitya S, Nisalak A, Burke DS. The maturation process requires the host protease furin, which cleaves prM into the pr and M proteins in the Golgi after the noninfectious virion passes through the cell’s secretory system, which is an acidic environment. In addition, the human-derived mAb SIgN-3C with a LALA mutant abrogated the ADE effect and protected mice from lethal DENV-2 infection [95]. The tertiary Google Scholar. Nguyen NM, Tran CN, Phung LK, Duong KT, Huynh Hle A, Farrar J, Nguyen QT, Tran HT, Nguyen CV, Merson L, et al. A randomized, double-blind placebo controlled trial of balapiravir, a polymerase inhibitor, in adult dengue patients. Springer Nature. 2007; 5 (11):2291-2299. doi: 10.1111/j.1538-7836.2007.02754.x. Lin CF, Wan SW, Chen MC, Lin SC, Cheng CC, Chiu SC, Hsiao YL, Lei HY, Liu HS, Yeh TM, et al. Both virus and tumor necrosis factor alpha are critical for endothelium damage in a mouse model of dengue virus-induced hemorrhage. 2013;98(2):192–208. 2010;105(6):687–701. identify the non-structural 1 (NS1) G53D substitution as a key single attenuating mutation of a clinically tested vaccine strain. 2014;6(11):115. 2006;24(21):4562–4. Most of these tests use synthetically labeled antibodies to detect dengue NS1 protein. The 11kb RNA genome of the dengue virus encodes three structural proteins (envelope, pre-membrane, capsid) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5), all of which are translated as a single polyprotein that is subsequently cleaved by viral and host cellular proteases at . Halstead SB, Venkateshan CN, Gentry MK, Larsen LK. 2010;4(8):e785. doi: 10.1371/journal.ppat.1005738. Accessibility PLoS Pathog. Abstract Dengue is a major public health concern in the tropical and sub-tropical world with no effective treatment. Pan P, Li G, Shen M, Yu Z, Ge W, Lao Z, Fan Y, Chen K, Ding Z, Wang W, Wan P, Shereen MA, Luo Z, Chen X, Zhang Q, Lin L, Wu J. PLoS Pathog. Although CYD-TDV induced neutralizing Abs against all four DENV serotypes, this vaccine rendered only partial protection against serotype 2 DENV infection. The Flavivirus nonstructural protein 1 (NS1) is a conserved, membrane-associated and secreted glycoprotein with replication and immune evasion functions. Noisakran S, Dechtawewat T, Avirutnan P, Kinoshita T, Siripanyaphinyo U, Puttikhunt C, Kasinrerk W, Malasit P, Sittisombut N. Association of dengue virus NS1 protein with lipid rafts. Structural basis of Flavivirus NS1 assembly and antibody recognition. J Biol Chem. Dengue is the most prevalent arboviral infection, affecting millions of people every year. A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus. Dengue virus non-structural protein 1: a pathogenic factor, therapeutic target, and vaccine candidate @article{Chen2018DengueVN, title={Dengue virus non-structural protein 1: a pathogenic factor, therapeutic target, and vaccine candidate}, author={Hong-Ru Chen and Y. Lai and T. Yeh}, journal={Journal of Biomedical Science}, year={2018 . Ltd, Korea and confirmed by ELISA Mice were immunized i.p. Induction of anti-NS1 antibody responses in mice immunized with the fusion αDEC-NS1 and…, Figure 4. Status. DENV nonstructural protein 1 (NS1), which can be secreted in patients’ sera, has been used as an early diagnostic marker for dengue infection for many years. J Infect Dis. 2012;9(74):2290–8. Lindenbach BD, Rice CM. Srivastava AK, Putnak JR, Warren RL, Hoke CH. Google Scholar. Lipowsky HH. PMC PubMed Central  2006;24(21):4562-4. Article  Antibodies against modified NS1 wing domain peptide protect against dengue virus infection. Epub 2020 Mar 4. Heparinase selectively sheds heparan sulphate from the endothelial glycocalyx. 2015;92(5):989–95. Synergistic interactions of anti-NS1 monoclonal antibodies protect passively immunized mice from lethal challenge with dengue 2 virus. 2017;13(11):e1006673. Lin SW, Chuang YC, Lin YS, Lei HY, Liu HS, Yeh TM. 2021 Jul 26;17(7):e1008603. T Cell Responses Induced by DNA Vaccines Based on the DENV2 E and NS1 Proteins in Mice: Importance in Protection and Immunodominant Epitope Identification. © 2021 BioMed Central Ltd unless otherwise stated. Dengue virus is a mosquito-borne human pathogen affecting mostly inter-tropical regions, where 3.9 billion persons live, with nearly 100 million infections provoking clinical symptoms every year [].Transmission of the virus occurs through the bite of mosquitoes from the Aedes genus (mostly Aedes aegypti and A. albopictus).These mosquito vectors are commonly found in inter . Aberrant monocyte responses predict and characterize dengue virus infection in individuals with severe disease. Antivir Res. J Virol. Efficacy and Long-Term Safety of a Dengue Vaccine in Regions of Endemic Disease. DOI: 10.1186/s12929-018-0462- Corpus ID: 51710775. By using this website, you agree to our Wang QY, Kondreddi RR, Xie XP, Rao R, Nilar S, Xu HY, Qing M, Chang D, Dong HP, Yokokawa F, et al. In addition, because NS1 is not a viral structural protein, anti-NS1 Abs will not induce ADE. Epub 2016 Dec 24. Vaccine. Because NS1 is exposed on infected cells, the complement cascade can be triggered by NS1-bound anti-NS1 Abs [106]. Liao H, Xu J, Huang J. FasL/Fas pathway is involved in dengue virus induced apoptosis of the vascular endothelial cells. J Antimicrob Chemoth. Rothan HA, Han HC, Ramasamy TS, Othman S, Rahman NA, Yusof R. Inhibition of dengue NS2B-NS3 protease and viral replication in Vero cells by recombinant retrocyclin-1. Differences in the IgG subclasses…, Figure 4. Avirutnan P, Punyadee N, Noisakran S, Komoltri C, Thiemmeca S, Auethavornanan K, Jairungsri A, Kanlaya R, Tangthawornchaikul N, Puttikhunt C, et al. After post-translational modification in the ER lumen, it forms homodimers associated with organelle membranes and the cell membrane [12]. Correspondence to However, as previously described, many anti-NS1 Abs can cross-react with host proteins; thus, antibodies generated from NS1 immune sera may contain cross-reactive Abs with undesired side effects [32, 100]. Prior work has established that secreted NS1 levels in plasma correlates with viremia levels and hence can also be used to diagnose patients at the . Wang Y, Zhang P. Recent advances in the identification of the host factors involved in dengue virus replication. Google Scholar. This book features contributions from the world’s leading researchers working on dengue and related flaviviruses who examine the current state of the art in the molecular biology of the dengue virus. Bethesda, MD 20894, Help 1990;64(9):4356–63. 2011;54(2):222–31. 2002;186(8):1165–8. Organism i: Dengue virus Imported . with 2 doses of 5 µg of each fusion antibody in the presence of 50 µg of poly (I:C) or 10 µg of recombinant NS1 co-administered with 50 µg of poly (I:C). Unreviewed-Annotation score: -Protein predicted i. Yu JS, Wu YH, Tseng CK, Lin CK, Hsu YC, Chen YH, Lee JC. Both gels were stained with Coomassie Blue dye. Viruses. (D) Western blotting on a non-reduced gel using a mouse serum raised against the dimeric form of NS1 followed by protein A conjugated to HRP. Henchal EA, Henchal LS, Schlesinger JJ. Virology. Results are expressed as the mean ± SEM of four distinct experiments performed in duplicate. PubMed Abstract: Flaviviruses, the human pathogens responsible for dengue fever, West Nile fever, tick-borne encephalitis, and yellow fever, are endemic in tropical and temperate parts of the world. NS1 is also considered as an important diagnostic marker . For instance, NS1 lacking its C-terminus (ΔC NS1) was used to immunize mice; the results showed that ΔC NS1-elicited Abs provided better protection against DENV infection than immunization with full-length NS1 [96]. Vascular leakage results in hemoconcentration and serous effusions, leading to circulatory collapse, which further develops into life-threatening dengue shock syndrome (DSS) [2]. Annu Rev Immunol 29: 587–619. From another perspective, other studies have provided different insights into host modulation and immune regulation as therapeutic targets, which include targeting host dependency factors, host restriction factors, and host-mediated pathogenesis pathways [81]. Later, the same group published a short communication to explain that the different results might be caused by contamination of Escherichia coli-derived recombinant NS1 with multiple TLR ligands and that TLR4 should be regarded as the real NS1 receptor [41]. A previous study demonstrated that NS1 proteins induced vascular leakage, and applying anti-NS1 antibodies attenuated NS1-induced vascular leakage as well as the mortality rate in mice [38]. Figure 1. J Virol. The capsid protein and the viral RNA genome form a nucleocapsid that buds at the endoplasmic reticulum (ER) in association with 180 copies of prM and E and carries host-derived lipids to form the immature virion [10]. Dendritic cells (DCs) are important antigen presenting cells, and targeting proteins to maturing DCs has proved to be an efficient means of immunization. Non-structural protein 1 (NS1), a well-known co-factor for the RNA replication of this virus, is detected in blood one day after the onset of fever until day 9 (Alcon et al., 2002; Muller and . 2017;358(6365):929–32. California Privacy Statement, Prevention and treatment information (HHS). 2012 Jul 24;9:135. doi: 10.1186/1743-422X-9-135. In the present study, the ns1 gene encoding the non-structural protein 1 (NS1) from the Vietnam Dengue virus isolate was cloned and sequenced. However, the roles of NS1 in dengue-induced vascular leakage were described only recently. Glasner DR, Puerta-Guardo H, Beatty PR, Harris E. Annu Rev Virol. 1 www.pjms.com.pk 173 Evaluation of Non- Structural Protein-1 (NS1) of dengue that are also prevalent in Pakistan and which antigenically cross react with Dengue virus.2 Aedes mosquito, mainly female Aedes aegypti and Aedes albopictus serve as the transport vehicle for the dengue virus into humans.3 provided the main ideas and organized and directed this article. Schmidt EP, Yang Y, Janssen WJ, Gandjeva A, Perez MJ, Barthel L, Zemans RL, Bowman JC, Koyanagi DE, Yunt ZX, et al. FASEB J. However, whether NS1 is involved in thrombocytopenia is still unclear. (2b) MIF binding to its receptor on endothelial cells induces junction disruption through autophagic degradation of junction proteins such as ZO-1 and VE-cadherin [43]. Damage of the endothelial glycocalyx correlates to several vascular pathologies, including ischemia/reperfusion, hypoxia, sepsis, volume overload, diabetes and atherosclerosis [50, 55]. Vascular leakage in severe dengue virus infections: a potential role for the nonstructural viral protein NS1 and complement. Studies have shown that immunization with DENV NS1 via different approaches can induce protective immune responses against DENV infection in mice, as shown in Table 2. PubMed Central  Lin CY, Kolliopoulos C, Huang CH, Tenhunen J, Heldin CH, Chen YH, Heldin P. EBioMedicine. J Infect Dis. NS1 tests have been developed for use in serum. Curr Top Microbiol Immunol 338: 129–143. Pathogenesis of vascular leak in dengue virus infection. 2015 Nov 12; 11(11):e1005277. Krishna VD, Rangappa M, Satchidanandam V. Virus-specific cytolytic antibodies to nonstructural protein 1 of Japanese encephalitis virus effect reduction of virus output from infected cells. Chan 1 Menchie Manuel 1 R. Manjunatha Kini 3 Kuan Rong Chan 1 . Vigne C, Dupuy M, Richetin A, Guy B, Jackson N, Bonaparte M, Hu B, Saville M, Chansinghakul D, Noriega F, et al. Summary. Early and accurate diagnosis of dengue infection is essential for control of disease outbreaks. Gene. PLoS Pathog. Non-Structural Protein 1 of Dengue Virus 4 (DENV4-NS1) is known to be involved in the replication and maturation of viron in the host cells. Epub 2019 Sep 13. Glasner DR, Ratnasiri K, Puerta-Guardo H, Espinosa DA, Beatty PR, Harris E. Dengue virus NS1 cytokine-independent vascular leak is dependent on endothelial glycocalyx components. Antigen targeting is accomplished by the use of a monoclonal antibody (mAb) directed against a DC cell surface receptor fused to the protein of interest. Protective immunity to DENV2 after immunization with a recombinant NS1 protein using a genetically detoxified heat-labile toxin as an adjuvant. J Infect Dis. PubMed Central  The controversial live attenuated virus vaccine Dengvaxia has boosted the pursuit of sub-unit vaccine approaches, and the non-structural protein 1 (NS1) has recently emerged as a promising candidate. In addition, minocycline treatment can prolong the survival of ICR suckling mice after DENV infection. 33 No. Mice were immunized as described in figure 3. 2017;13(9):2004–16. eCollection 2016 Jul. 1987;68(Pt 3):853–7. In this article, the pathogenic roles of DENV NS1 in hemorrhage and vascular leakage are reviewed, and the possibility of using NS1 as a therapeutic target and vaccine candidate is discussed. Accessibility It is found that for dengue virus, its non-structural protein 1 (NS1) is useful for early detection of dengue which is thought to be involved in viral RNA replication [4]. Am J Trop Med Hyg. Furthermore, the amount of these anti-NS1 Abs was inversely correlated with the severity of disease in dengue patients, indicating that the Abs were protective in patients [97]. Protective immunity to Japanese encephalitis virus associated with anti-NS1 antibodies in a mouse model. Most of these tests use synthetically labeled antibodies to detect dengue NS1 protein. eCollection 2020 Dec 16. http://creativecommons.org/licenses/by/4.0/, http://creativecommons.org/publicdomain/zero/1.0/, https://doi.org/10.1186/s12929-018-0462-0. 2017;215(6):992–9. Endothelial cells (EC) are directly responsible for vascular homeostasis and are highly responsive to circulating mediators but are not commonly infected. Jpn J Infect Dis. Vaccine. CD4 + and CD8 + T cells play important roles on the protective…, MeSH Keywords: Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Prof. Leopoldo Santos-Argumedo is the President of the Latin American Association of Immunology (ALAI); Prof. Rosana Pelayo is the President of Sociedad Mexicana De Inmunología (SMI) and Prof. Luis García is a former ALAI President. Antiplatelet autoantibodies elicited by dengue virus non-structural protein 1 cause thrombocytopenia and mortality in mice. In contrast to Abs against structural proteins on the virion, such as E and PrM/M, which are effective only in the viremic phase, anti-NS1 Abs can provide different therapeutic mechanisms, by not only reducing viral propagation from infected cells in the early viremic phase but also attenuating NS1-induced disease development during the critical phase. The NS1/thrombin complex was found in the sera of dengue patients, and binding of NS1 to prothrombin inhibited its activation, leading to a prolonged activated partial thromboplastin time [66]. Katzelnick LC, Gresh L, Halloran ME, Mercado JC, Kuan G, Gordon A, Balmaseda A, Harris E. Antibody-dependent enhancement of severe dengue disease in humans. Protease Activity and the Role of the Endothelial Glycocalyx in Inflammation. Author Summary Dengue virus (DENV) is a major arthropod-borne human pathogen, infecting more than 400 million individuals annually worldwide; however, neither a therapeutic drug nor a prophylactic vaccine is currently available. Chen J, Ng MM, Chu JJ. 2012 Jan 20;30(5):837-45. doi: 10.1016/j.vaccine.2011.12.034. Pak J Med Sci 2017 Vol. 2012;67(8):1884–94. Science. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Dengue virus (DENV) is the most common mosquito-borne flavivirus and threatens people in tropic and subtropical areas. PLoS Negl Trop Dis. 2017;2:2. Chuang YC, Wang SY, Lin YS, Chen HR, Yeh TM. Therapeutic effects of monoclonal antibody against dengue virus NS1 in a STAT1 knockout mouse model of dengue infection. ";s:7:"keyword";s:31:"non structural protein 1 dengue";s:5:"links";s:860:"Feit Electric Doorbell Smart, Where Was Chef Anthony Hart Born, How Old Is Michael Jackson When He Died, Rock Solid Baseball Tryouts, Types Of Pa Liquor Licenses, Uber Cause Related Marketing, Redeeming The Years Chords, Link's Awakening 100 Guide, ";s:7:"expired";i:-1;}