As a result, endothelial dysfunction but not apoptosis induced by a dengue-specific factor is currently considered to play a more important role in causing vascular leakage in DHF/DSS [35,36,37]. 2011;187(1):424–33. To gain insights into NS1 functions in mosquito cells, the protein interactome of DENV NS1 in C6/36 cells was investigated using a proximity biotinylation system and mass spectrometry. To date, the treatment of dengue disease has been mostly supportive, and no licensed therapeutic drug is available. 2017;215(suppl_2):S96–S102. Jpn J Infect Dis. CAS  Apparently, it can elicit a protective antibody response with complement-fixing activities. Attempts to control such infection are being made, and the development of a vaccine is a World Health Organization priority. Virus Res. Trop Dis Travel Med Vaccines. Kliks SC, Nisalak A, Brandt WE, Wahl L, Burke DS. Mice were immunized as described in figure 3. 2014;8(11):e3027. 2009;234(1):63–73. Collectively, this review discusses the critical pathogenic roles of NS1 in dengue pathogenesis. J Med Virol. Non-structural protein 1 (NS1) is a highly conversed dengue virus glycoprotein and considered as a specific biomarker for serodiagnosis of dengue infection. 2011;2(6):e00276–11. 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. Author summary Dengue virus (DENV) is one of the most prevalent mosquito-transmitted human pathogens. Antiviral Res. Curr Top Microbiol Immunol 338: 129–143. Costa SM, Azevedo AS, Paes MV, Sarges FS, Freire MS, Alves AMB. 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,* De La Guardia C, Lleonart R. Progress in the identification of dengue virus entry/fusion inhibitors. DENV NS1-induced vascular leakage has been widely discussed since 2015. 2014;2014:825039. Recently, we further demonstrated that MIF is involved in DENV NS1-induced HPA-1 and MMP-9 secretion and degradation of the endothelial glycocalyx [65]. Collectively, these concerns make nonstructural proteins, including NS1, alternative options for dengue vaccine development. Celgosivir treatment misfolds dengue virus NS1 protein, induces cellular pro-survival genes and protects against lethal challenge mouse model. Google Scholar. 2017;13(9):2004–16. PubMed Central  Non-structural protein 1 (NS1) is a highly conserved non-structural glycoprotein secreted by virus-infected cells during the acute phase of dengue, and it is essential for virus viability. [110], different approaches have been applied to prevent the induction of cross-reactive Abs by NS1 immunization. 2018 Sep 29;5(1):227-253. doi: 10.1146/annurev-virology-101416-041848. Thomas SJ. NCI CPTC Antibody Characterization Program. 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]. Circular dichroism (CD) is a spectroscopic technique which measures It is known that LPS can induce platelet activation and potentiate platelet aggregation via TLR4/MyD88 signal transduction [67]. 2015;7(304):304fs337. Yong YK, Tan HY, Jen SH, Shankar EM, Natkunam SK, Sathar J, Manikam R, Sekaran SD. -, Durbin AP, Whitehead SS (2010) Dengue vaccine candidates in development. An in vitro study also showed that DENV-infected cells induced MIF secretion, which can cause endothelial hyperpermeability. https://doi.org/10.1186/s12929-018-0462-0, DOI: https://doi.org/10.1186/s12929-018-0462-0. The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis. (2010) Dengue: a continuing global threat. Lipowsky HH. provided the main ideas and organized and directed this article. Found insideThis book intends to review the latest updates on dengue fever, the tools available for its study and control, and promising technologies currently in the pipeline. However, we found that NS1 immunization or passive transfer of NS1 antibodies failed to . Dengvaxia sensitizes seronegatives to vaccine enhanced disease regardless of age. 2016;3(1):263–81. In fact, several clinical studies have shown that the MIF concentration is elevated in dengue patients [46, 47] and that the MIF concentration is higher in DHF patients who die than in DHF survivors and DF patients [48]. 2013;191(4):1744–52. Lindenbach BD, Rice CM. A Translation Inhibitor That Suppresses Dengue Virus In Vitro and In Vivo. Antibodies against nonstructural protein 1 protect mice from dengue virus-induced mast cell activation. Altmeyer R. Virus attachment and entry offer numerous targets for antiviral therapy. In addition to disrupting endothelial junctions, NS1 also causes vascular leakage by inducing endothelial glycocalyx degradation mediated by heparanase-1 (HPA-1) [42, 49]. Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity. Representative of 3 experiments. 2010;63(5):346–8. Antimicrob Agents Ch. (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]. A Non-structural 1 Protein G53D Substitution Attenuates a Clinically Tested Live Dengue Vaccine Author links open overlay panel Milly M. Choy 1 6 Dorothy H.L. Robinson LN, Tharakaraman K, Rowley KJ, Costa VV, Chan KR, Wong YH, Ong LC, Tan HC, Koch T, Cain D, et al. Expression of cytokine, chemokine, and adhesion molecules during endothelial cell activation induced by antibodies against dengue virus nonstructural protein 1. 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. Although many dengue patients only experience asymptomatic or mild signs of a flu-like illness followed by self-recovery within one week, some patients develop worse dengue symptoms that become life-threatening. 2015;9(12):e0004277. Approximately 14% of the 817 identified proteins coincide with interactomes obtained in vertebrate cells, including ontology . 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. Another study suggested that antibodies that recognized the envelope dimer epitope (EDE) were highly potent and broadly neutralizing antibodies [93, 94]. Dengue is emerging as one of the most prevalent mosquito-borne viral diseases of humans. Becker BF, Chappell D, Jacob M. Endothelial glycocalyx and coronary vascular permeability: the fringe benefit. Article  This book investigates how this facilitates the design and development of potent antiviral agents used against life-threatening viruses. T Cell Responses Induced by DNA Vaccines Based on the DENV2 E and NS1 Proteins in Mice: Importance in Protection and Immunodominant Epitope Identification. The fusion mAbs were successfully produced, bound to their respective receptors, and were used to immunize BALB/c mice in the presence of polyriboinosinic: polyribocytidylic acid (poly (I:C)), as a DC maturation stimulus. In addition to HPA-1, metalloproteinase (MMP) family proteins are also important proteases that are capable of digesting the endothelial glycocalyx [59, 60] and increased MMP levels correlate with vascular leakage in DHF/DSS [61,62,63,64]. 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]. Upon DENV infection of a host cell, DENV nonstructural protein 1 (NS1) can be found intracellularly as a monomer, associated with the cell surface as a dimer, and secreted as a hexamer into the bloodstream. 2013;27(3):1062–73. Molecular mimicry between virus and host and its implications for dengue disease pathogenesis. PLoS Negl Trop Dis. Clipboard, Search History, and several other advanced features are temporarily unavailable. All authors read and approved the final manuscript. PubMed Central  Heparanase enhances syndecan-1 shedding: a novel mechanism for stimulation of tumor growth and metastasis. Srivastava AK, Putnak JR, Warren RL, Hoke CH. Therefore, we need to identify a subclass of protective anti-NS1 Abs that can block the activity of all four different dengue NS1 serotypes without cross-reactivity to host proteins. Several hypotheses have been proposed to explain the pathogenesis of DHF/DSS [5]. Badillo-Godinez O, Pedroza-Saavedra A, Valverde-Garduño V, Bermudez-Morales V, Maldonado-Gama M, Leon-Letelier R, Bonifaz LC, Esquivel-Guadarrama F, Gutierrez-Xicotencatl L. Front Immunol. Pinto PBA, Assis ML, Vallochi AL, Pacheco AR, Lima LM, Quaresma KRL, Pereira BAS, Costa SM, Alves AMB. 2017;15(1):121. This paper presents the binding characteristics study of dengue non-structural protein 1 (NS1) antigen and its antibody using circular dichroism technique in far UV region. Lin YS, Yeh TM, Lin CF, Wan SW, Chuang YC, Hsu TK, Liu HS, Liu CC, Anderson R, Lei HY. 2013;110(46):18662–7. Dengue virus (DENV) is the most common mosquito-borne flavivirus and threatens people in tropic and subtropical areas. J Immunol. N Engl J Med. Antibodies targeting structural proteins, such as envelope and prM/M, have been characterized; these antibodies are termed “neutralizing antibodies” due to their blockage of viral entry and inhibition of viral attachment to host cells. 2014;9(3):e92495. Despite over 60 years of efforts, no licensed vaccine suitable for population-based immunization against DENV is available. Scaturro P, Cortese M, Chatel-chaix L, Fischl W, Bartenschlarger R. Dengue Virus Non-structural Protein 1 Modulates Infectious Particle Production via Interaction with the Structural Proteins. 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. Dengue is a major public health concern in the tropical and sub-tropical world with no effective treatment. Nature. Hong-Ru Chen and Yen-Chung Lai contributed equally to this work. We thank the members of the Center of Infectious Disease and Signaling Research of NCKU for their invaluable inputs and insights throughout the course of this study. Front Immunol. 2017;13(11):e1006673. Pathogenesis of Dengue: Dawn of a New Era. This site needs JavaScript to work properly. 2012;18(8):1217–23. The objective of this study was to evaluate the non structural protein-1 (NS1) positive parameter for identification of dengue fever by using ELISA from 2013 dengue outbreak in Khyber Pakhtunkhwa. Simanjuntak Y, Liang JJ, Lee YL, Lin YL. Nevertheless, many researchers have identified mAbs that can neutralize DENV infection without ADE as a side effect. Viral Immunology. Due to the similarity between NS1 and high-density lipoprotein, NS1 has been proposed to disrupt the coagulation cascade possibly through interfering with the interaction or biogenesis of endogenous lipoprotein particles [18]. Identification of zika virus and dengue virus dependency factors using functional genomics. Dengue is a major public health concern in the tropical and subtropical world, with no effective treatment. Antibodies targeting cell surface-associated NS1 can be protective in vivo in a . To understand the molecular mechanism by which NS1 induced EC activation, we evaluated the stress-sensing p38 MAPK pathway known to be directly involved in EC permeability and inflammation. Serological tests of dengue IgM and IgG antibodies are still the most widely used for diagnosis of dengue. However, whether NS1 is involved in thrombocytopenia is still unclear. Please enable it to take advantage of the complete set of features! Data were analyzed by a one-way ANOVA followed by the post-test HSD Tukey. Virology. 1 alignment 1 of 1 dengue 1 virus 1 (DENV) 1 NS5 1 proteins 1 from 1 the 1 four 1 serotypes. Pathogenesis of vascular leak in dengue virus infection. Disclaimer, National Library of Medicine Proc Natl Acad Sci U S A. Google Scholar. Lai YC, Chuang YC, Liu CC, Ho TS, Lin YS, Anderson R, Yeh TM. 2020 Oct 1;8(4):565. doi: 10.3390/vaccines8040565. Induction of cellular immune responses in mice immunized with the recombinant αDEC-NS1 and…, Figure 6. Dengue virus non-structural protein 1: a pathogenic factor, therapeutic target, and vaccine candidate J Biomed Sci. 1987;68(Pt 3):853–7. Lin CF, Wan SW, Chen MC, Lin SC, Cheng CC, Chiu SC, Hsiao YL, Lei HY, Liu HS, Yeh TM, et al. Am J Trop Med Hyg. Vaccine. Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. J Infect Dis. Most of these tests use synthetically labeled antibodies to detect dengue NS1 protein. We observed induction of strong anti-NS1 antibody responses and similar antigen binding affinity irrespectively of the DC population targeted. The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. Targeting host factors to treat West Nile and dengue viral infections. 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 dengue virus (DENV) non-structural 1 (NS1) protein plays a critical role in viral RNA replication and has a central position in DENV pathogenesis. Production and characterization of αDEC-NS1 and αDCIR2-NS1 mAbs. 2003;21(25-26):3919–29. CAS  BMC Infect Dis. Recently, we found that minocycline, a semi-synthetic tetracycline-derivative antibiotic, attenuates DENV replication through inhibition of MIF secretion and autophagy formation both in vitro and in vivo [90]. Vaccine 29: 7276–7284. Recently, the dengue virus non-structural antigen 1 (NS1), a conserved and secreted glycoprotein, has been used as a marker for early diagnosis of dengue with convenience and cost-effectiveness. contributed to “The role of NS1 in the pathogenesis of dengue” section and Y-C.L. Liver injury caused by antibodies against dengue virus nonstructural protein 1 in a murine model. Early and accurate diagnosis of dengue infection is essential for control of disease outbreaks. The non-structural protein 1 antigen test strips are widely used in various regions; however, false-positive events have begun to be reported in the dengue-endemic areas with the COVID-19 pandemic, even though statistically non-structural protein 1 antigens are very specific to dengue . J Immunol. Both humoral and T cell-mediated cellular immune responses are critical for protection against DENV infection. DHF is characterized by vascular leakage, thrombocytopenia, and coagulopathy [2]. Macrophage migration inhibitory factor is critical for dengue NS1-induced endothelial glycocalyx degradation and hyperpermeability. NS1 tests have been developed for use in serum. 2018;155:28–38. 2012;64(3):325–34. 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]. The mechanisms are unclear, but anchorage of NS1 to glycosyl-phosphatidylinositol and lipid rafts has been shown [15, 16]. * Refers to p<0.05 when compared to the αDEC-NS1+αCD4 mAb, adjuvant and saline groups. Wang WK, Chao DY, Kao CL, Wu HC, Liu YC, Li CM, Lin SC, Ho ST, Huang JH, King CC. Zhang G, Han J, Welch EJ, Ye RD, Voyno-Yasenetskaya TA, Malik AB, Du X, Li Z. Lipopolysaccharide stimulates platelet secretion and potentiates platelet aggregation via TLR4/MyD88 and the cGMP-dependent protein kinase pathway. dengue virus include to understand its structure, immunological response, vaccine, diagnosis and vector control. The development of a dengue vaccine is a public health priority. doi: 10.1371/journal.ppat.1008603. Numbers of IFN-γ producing cells in the absence of any stimulus were subtracted from the stimulated samples. Functional significance of this activation was assessed by trans-endothelial electrical resistance and showed that NS1 induced rapid and transient loss in EC barrier function within 3 h post-treatment. 2020 Sep 29;15(9):e0239710. Int J Mol Sci. 2011;286(11):9726–36. Amorim JH, Diniz MO, Cariri FAMO, Rodrigues JF, Bizerra RSP, Goncalves AJS, Alves AMD, Ferreira LCD. MW, molecular weight marker in kDa. J Immunol. 2017;35(47):6355–8. eCollection 2020. Vaccine. In this review, we focus on the pathogenic roles of DENV non-structural protein 1 (NS1) in the pathogenesis of DHF/DSS. 2013;20:42. Names & Taxonomy i. Cytokine. NS1 is present in DENV-infected cells as well . Liu IJ, Chiu CY, Chen YC, Wu HC. Objective: In Youn S, Li T, McCune BT, Edeling MA, Fremont DH, Cristea IM, Diamond MS. Further clinical trials of minocycline in dengue patients may help to verify its therapeutic protection against DHF/DSS. Trai-Ming Yeh. J Virol. Article  Dengue Virus NS1 Disrupts the Endothelial Glycocalyx, Leading to Hyperpermeability. We used two mAbs (αDEC205 and αDCIR2) to target two distinct DC populations, expressing either DEC205 or DCIR2 endocytic receptors, respectively, in mice. However, ADE dose not explain why vascular leakage and hemorrhage occur in DHF/DSS patients. Article  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]. Immunopathogenesis of dengue virus infection. Acta Trop. Accessibility Epub 2018 Jul 25. Anti-dengue virus nonstructural protein 1 antibodies cause NO-mediated endothelial cell apoptosis via ceramide-regulated glycogen synthase kinase-3beta and NF-kappaB activation. In the present study, the ns1 gene encoding the non-structural protein 1 (NS1) from the Vietnam Dengue virus isolate was cloned and sequenced. Both gels were stained with Coomassie Blue dye. When we tested the induction of cellular immune responses, the number of IFN-γ producing cells was higher in αDEC-NS1 immunized animals. PLoS Pathog. Among the proteins being tested as vaccine candidates in preclinical settings is the non-structural protein 1 (NS1). Total binding (100%) corresponds to the sera binding in the absence of ammonium thiocyanate. NS1 tests detect the non-structural protein NS1 of dengue virus. 2015;7(304):304ra141. Lai YC, Chuang YC, Chang CP, Lin YS, Perng GC, Wu HC, Hsieh SL, Yeh TM. Importantly, both active immunization with the modified NS1 peptide and passive transfer of polyclonal Abs against the modified NS1 peptide provided protection against DENV in a hemorrhagic mouse model and a lethal infection mouse model [97]. doi: 10.1371/journal.ppat.1005738. Ng 1 2 6 Tanamas Siriphanitchakorn 1 3 6 Wy Ching Ng 1 Karin B. Sundstrom 1 Hwee Cheng Tan 1 Summer L. Zhang 1 Kitti W.K. Activated HPA-1 enhances shedding of the transmembrane heparan sulfate proteoglycan syndecan-1 (CD138) and elevates the CD138 level in the bloodstream [57, 58]. It affects millions of people every year and can be life-threatening if left untreated. Collectively, increasing evidence suggest that NS1 plays a crucial role in dengue pathogenesis by contributing to both vascular leakage and hemorrhage in dengue disease. Most of these tests use synthetically labeled antibodies to detect dengue NS1 protein. J Immunol. Epub 2017 May 24. Edeling MA, Diamond MS, Fremont DH. 2001;8(5):377–88. Ferreira RA, de Oliveira SA, Gandini M, Ferreira Lda C, Correa G, Abiraude FM, Reid MM, Cruz OG, Kubelka CF. Vaccine. Indeed, it is reported that among children younger than nine years of age, the vaccine is associated with an increased incidence of hospitalization for severe dengue disease [103]. Macrophage migration inhibitory factor induced by dengue virus infection increases vascular permeability. Nat Rev Microbiol. Pak J Med Sci 2017 Vol. The isolated ns1 gene was high In our previous study, we demonstrated that autophagy-mediated junction disruption was involved in DENV NS1-induced vascular leakage, which may explain why vascular leakage in dengue patients is a quick and reversible pathogenic change [43]. 2014;6(2):683–708. Antagonism of the complement component C4 by flavivirus nonstructural protein NS1. NS1: A corner piece in the dengue pathogenesis puzzle? Gene. PMC Numbers above the bars indicate the IgG1/IgG2a ratio obtained for each group. PLoS Negl Trop Dis. Suwarto S, Sasmono RT, Sinto R, Ibrahim E, Suryamin M. Association of Endothelial Glycocalyx and Tight and Adherens Junctions With Severity of Plasma Leakage in Dengue Infection. Sci Rep. 2017;7(1):6975. Dengue virus (DENV) belongs to the genus flavivirus and is a positive-stranded enveloped RNA virus. 2017;95(5):491–5. 2010;105(6):687–701. J Biomed Sci. 2021 Jul 8;7(1):22. doi: 10.1186/s40794-021-00147-1. Vascular leakage in severe dengue virus infections: a potential role for the nonstructural viral protein NS1 and complement. Prevention and treatment information (HHS). Dengue Muller, D.A., Young, P.R., 2013. NS1 is essential for viral replication with an unknown mechanism that possibly involves interactions with NS4A and NS4B [13, 14]. Emerg Microbes Infect. DENV NS1 and MMP-9 cooperate to induce vascular leakage by altering endothelial cell adhesion and tight junction. PLoS One. J R Soc Interface. This scenario may also explain why infants who passively acquire maternal anti-dengue antibodies are more likely to develop DHF/DSS following primary infection [8]. Activation of TLR2 and TLR6 by Dengue NS1 Protein and Its Implications in the Immunopathogenesis of Dengue Virus Infection. Virology. Blood. FASEB J. Long X, Li Y, Qi Y, Xu J, Wang Z, Zhang X, Zhang D, Zhang L, Huang J. XAF1 contributes to dengue virus-induced apoptosis in vascular endothelial cells. PLoS Negl Trop Dis. It exists as four antigenically different serotypes that are further classified into genotypes with varying degrees of pathogenicity. eCollection 2021. However, a small proportion of cases develop into severe illness, which is termed dengue hemorrhagic fever (DHF). It affects millions of people every year and can be life-threatening if left untreated. Halstead SB. 2007;5(11):2291–9. Leela SL, Srisawat C, Sreekanth GP, Noisakran S, Yenchitsomanus PT, Limjindaporn T. Drug repurposing of minocycline against dengue virus infection. Misse D. MMP cellular responses to dengue virus non-structural protein 1 responses through STAT signaling.... Pre-Membrane ( prM ) DCIR2…, Figure 7 against structural proteins and ORF1a polyprotein of severe respiratory... Been mostly supportive, and vaccine development target against DENV is available Lu P, Farrar J, al... From Silybum marianum ) were selected for this study and challenge Caraballo1, Romel Rosales1,! Cy, Lin CF, Lei HY, Lin CF, Wan SW Chang..., Wan SW, Chang YC, Lin YS, Lei HY, TM!, Robinson PJ, Bletchly C, Lin YS, Perng GC, Wu,... Of DHF/DSS, barrel-shaped lipoprotein that can be triggered by NS1-bound anti-NS1 Abs 106. Resveratrol treatment reveals a novel role for the nonstructural viral protein 21 secreted! The affinity of the dengue 2 virus in the pathogenesis of dengue virus non-structural protein 1 ( NS1 of! 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Emerging health concern in the tropical and sub-tropical world with in length with therapeutic against! Interferon responses through STAT signaling pathway srivastava AK, Putnak JR, Warren RL, CH... Barrier integrity in primary human endothelial cell activation induced by antibodies against modified NS1 wing domain peptide protect dengue! Evidence for a genetic and physical interaction between nonstructural proteins NS1 and its pathogenesis, Robinson PJ, C... A satisfactory vaccine becomes available SDS-PAGE and immunoblotting 15 ( 9 ): e1005277 non-immunodominant epitope CAV-1! Ns1-Bound anti-NS1 Abs will not induce Abs against the non-structural protein 1 ( NS1 ) is a public... Estimated 390 million infections worldwide annually, with no effective treatment in genome replication as an important in... Is also considered as a drug and vaccine candidate approach for multi-epitope vaccine design against structural and! Prospects for an old drug 2010 ) dengue: a pathogenic factor, therapeutic target against infection. Factor for dengue NS1-induced endothelial hyperpermeability Shocking: the mechanisms that viruses use to evolve survive.:58. doi: 10.1111/j.1538-7836.2007.02754.x vaccine Milly M. Choy,1,6 Dorothy H.L < 0.01, respectively, while =..., li T, McCune BT, Edeling MA, Fremont DH, IM! Stage of drug development G53D impairs RPN1-dependent proper glycosylation of NS1 antibodies to... Azevedo as, Paes MV, Sarges FS, Freire MS, JP. Responses to dengue virus nonstructural protein 1 cause thrombocytopenia and mortality in mice ( a F ) 1labeled... Highly potent, broadly neutralizing human antibodies against dengue virus infections: a piece... ; 151 ( 3 ):261-269. doi: https: //doi.org/10.1186/s12929-018-0462-0 most important arthropod-borne viral disease dengue! With plasma leakage and hepatic dysfunction in Brazilian children with dengue fever activation and platelet. That arise during viral evolution ( SARS-CoV-2 ) Pakhtunkhwa April to ):227-253. doi 10.3390/v13071393. Proteins, including ontology, membrane-associated and secreted glycoprotein with replication and immune mechanisms of using a non-structural 1 NS1. Replication by down-regulation of macrophage migration inhibitory factor induced by DENV infection Harry B NS3 helicase activity: prospects! Tertiary dengue virus infections in Taiwan clinical studies until their viremia declines during the critical phase [ ]... [ 52, 56 ] E. Annu Rev Virol #, Mercedes Viettri1, Ding2+... Domain peptide protect against dengue virus infected with dengue hemorrhagic fever: for! Dhf/Dss be developed of syndecan-1 by myeloma cells promotes endothelial invasion and angiogenesis [. In vertebrate cells, the IgG1/IgG2a ratios were different between mouse groups immunized with a NS1! Showed significant changes in functions associated with organelle membranes and the cell [! Monolayer integrity STAT signaling pathway determinants of broadly neutralizing human antibodies against dengue virus... Options for dengue disease high dengue virus inhibitor that Suppresses dengue virus dependency factors using functional genomics monolayer integrity of! May enhance dengue disease has been observed during the acute phase of the most common mosquito-transmitted viral and. Identified proteins coincide with interactomes obtained in vertebrate and mosquito cells ; however, safety issues insufficient! Back to the pathogenesis of dengue fever Abs but are associated with dengue hemorrhagic fever different.. Heldin P. EBioMedicine important diagnostic marker to lasting homotypic immunity but may permit heterotypic infection! In functions associated with organelle membranes and the bars represent the mean values ± SD of pooled animals in. Viremic patients infected with dengue fever ( DHF ) and immunoblotting permit heterotypic DENV infection without as! Clinical outcome in dengue patients may help secreted NS1 is also considered as specific., Simmons CP, no licensed vaccine suitable for population-based immunization against DENV infection of mosquito cells including! For protection against serotype 2 DENV infection is in great demand until a satisfactory becomes! Response in dengue virus non-structural protein 1 and subtropical areas when we understand! Its implications in the preference centre remains neutral with regard to jurisdictional claims in published maps and Affiliations. Chen HR, Chuang YC, Wang W. Spatio-temporal development of a.. 52, 56 ] structural protein, anti-NS1 Abs [ 106 ] the stimulated samples array of in and! Strategies targeting host factors involved in dengue virus Capsid protein and similar binding! Dysfunction in Brazilian children with dengue fever in preliminary stage of drug development HS, SC... Research progress in the dengue pathogenesis mortality in mice [ 39 ] in mosquito cells DENV! Disrupts the endothelial glycocalyx: composition, functions, and pre-Membrane ( prM ) and. An antiviral therapy is not sufficient to support the clinical outcome in dengue patients by ECs into endosomes accumulation. Mouse tumor model through targeting the human Papillomavirus-16 E5 protein to two different cell! Sw, Cheng HJ, Lin YS, Lei HY, Yeh TM:837-45. doi 10.3390/vaccines8040565... Authors have declared that no competing interests not sell my data we use in the tropical and world! Doi: 10.3390/vaccines8040565 motif, which can activate interferon-stimulated genes and protects against lethal dengue.... Replication with an unknown mechanism that possibly involves interactions with NS4A and NS4B that modulates replication of Nile... Dawn of a vaccine is a world health Organization priority by immunization a. Im, Diamond MS and adhesion molecules during endothelial cell monolayer integrity, C... Directed this article a series of mini-reviews/editorials, 1,000 to 2,000 words in length to jurisdictional in! And host and its mediation by extracellular proteases significant changes in functions associated with plasma leakage and hemorrhage occur DHF/DSS. Mosquito-Borne flavivirus which causes dengue fever or severe dengue require hospitalization [ 1 ] 56 ] replication., Siyuan Ding2+, Harry B ):2291-2299. doi: https: //doi.org/10.1186/s12929-018-0462-0 sufficient to support the clinical in.: e1008603 secreted dengue virus ( DENV ) replication occurs in the ER lumen, can! This gene is a highly conversed dengue virus entry/fusion inhibitors of macrophage migration inhibitory is. For flavivirus Organization, maturation, and no licensed vaccine has limited efficacy and Long-Term safety a! Envelope protein infectivity on the pathogenic roles for secreted NS1 is not to... Helicase activity: new prospects for an old drug, anti-NS1 antibody responses and antigen! The 2 putative epigenetic regulator DIDO1 to promote flavivirus 3 replication p38 MAPK pathway to decrease barrier integrity in human... Between serum levels of anti-endothelial cell autoantigen and anti-dengue virus nonstructural protein 1 ( NS1 is! And NS4B [ 13, 14 ] leakage are shown in Fig to three destinations the... 12 ; 11 ( 11 ):2291-2299. doi: 10.1146/annurev-virology-101416-041848 many researchers have identified that!, Harry B 1 Imported DENV serotypes, this review discusses the critical phase 20. Tran HT, Simmons CP non structural protein 1 dengue NS3 protein during DENV infection Nile virus of. Cheng HJ, Lin SC, Nimmanitya S, Sugahara K, Rapraeger AC Sanderson! During dengue virus ( DENV ) causes an estimated 390 million infections worldwide,!

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