scholarly journals Monoclonal Antibodies That Bind to Common Epitopes on the Dengue Virus Type 2 Nonstructural-1 and Envelope Glycoproteins Display Weak Neutralizing Activity and Differentiated Responses to Virulent Strains: Implications for Pathogenesis and Vaccines

2007 ◽  
Vol 15 (3) ◽  
pp. 549-561 ◽  
Author(s):  
Andrew K. I. Falconar
Keyword(s):  
Monoclonal Antibodies ◽  
Dengue Virus ◽  
Neutralizing Activity ◽  
Denv Serotypes ◽  
Cross Reactions ◽  
Virulent Strains ◽  
Highly Virulent ◽  
Dengue Virus Type 2

ABSTRACT The abilities of monoclonal antibodies (MAbs) that bind to defined sequential epitopes on the dengue virus (DENV) nonstructural-1 (NS1) glycoproteins to cross-react with epitopes on the DENV envelope (E) glycoproteins were investigated. In this study, some of these MAbs cross-reacted with the DENV type 2 (DENV-2) E glycoprotein and with synthetic peptides representing X-ray crystallographically confirmed surface-exposed regions on this glycoprotein. MAb 1G5.3 cross-reacted with the flavivirus-conserved 101-WGNGCGLFG-109 fusion sequence, the 273-SSGNL-277 DENV-2 hinge region sequence, and the 156-GKHGKEIKIT-165 sequence of virulent DENV-2 strains. MAb 1G5.4-A1-C3 cross-reacted with the 67-NTTT ESR CPT-76 and 156-GKHGK EIK IT-165 sequences of virulent DENV-2 strains, the 338-EIMDL DNR HV-347 sequence from a highly virulent DENV-2 (M2) strain, and two epitopes on a virulent DENV-3 strain (288-KMD KLELK G-296 and 323- RVEYRGE DAP-332), which all contained target ELK/KLE-type motifs (underlined). These MAbs showed reduced cross-reactions with the corresponding sequences from weakly pathogenic strains of all four DENV serotypes and had either no (MAb 1G5.4-A1-C3) or weak (MAb 1G5.3) neutralizing activity against them. MAb 1G5.3 more strongly neutralized DENV-2 strains with higher pathogenic capacities, while MAb 1G5.4-A1-C3 showed increasing neutralizing titers against the virulent DENV-3 strain and the moderately virulent and highly virulent (M2) DENV-2 strains. These cross-reactions with the E glycoprotein accord with the observation that MAb 1G5.3 caused dramatic and lethal antibody-enhanced replication (AER) of a DENV-2 strain in vivo. Together with in vivo AER studies of these DENV strains using MAb 1G5.4-A1-C3, these results may account for the increased pathogenic capacities of such strains, which is likely to have important implications for pathogenesis and vaccines.

scholarly journals Development of VHH Antibodies against Dengue Virus Type 2 NS1 and Comparison with Monoclonal Antibodies for Use in Immunological Diagnosis

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e95263 ◽  
Author(s):  
Aneela Fatima ◽  
Haiying Wang ◽  
Keren Kang ◽  
Liliang Xia ◽  
Ying Wang ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Dengue Virus ◽  
Virus Type ◽  
Immunological Diagnosis ◽  
Vhh Antibodies ◽  
Dengue Virus Type 2

scholarly journals Infectious clone construction of dengue virus type 2, strain Jamaican 1409, and characterization of a conditional E6 mutation

2006 ◽  
Vol 87 (8) ◽  
pp. 2263-2268 ◽  
Author(s):  
Dennis J. Pierro ◽  
Ma Isabel Salazar ◽  
Barry J. Beaty ◽  
Ken E. Olson
Keyword(s):  
Cell Culture ◽  
Dengue Virus ◽  
Virus Type ◽  
Mammalian Cells ◽  
Infectious Clone ◽  
Cell Types ◽  
Dengue Virus Type 2

A full-length infectious cDNA clone (ic) was constructed from the genome of the dengue virus type 2 (DENV-2) Jamaica83 1409 strain, pBAC1409ic, by using a bacterial artifical chromosome plasmid system. Infectious virus was generated and characterized for growth in cell culture and for infection in Aedes aegypti mosquitoes. During construction, an isoleucine to methionine (Ile→Met) change was found at position 6 in the envelope glycoprotein sequence between low- and high-passage DENV-2 1409 strains. In vitro-transcribed genomic RNA of 1409ic with E6-Ile produced infectious virions following electroporation in mosquito cells, but not mammalian cells, while 1409ic RNA with an E6-Met mutation produced virus in both cell types. Moreover, DENV-2 1409 with the E6-Ile residue produced syncytia in C6/36 cell culture, whereas viruses with E6-Met did not. However, in vitro cell culture-derived growth-curve data and in vivo mosquito-infection rates revealed that none of the analysed DENV-2 strains differed from each other.

scholarly journals Type- and Subcomplex-Specific Neutralizing Antibodies against Domain III of Dengue Virus Type 2 Envelope Protein Recognize Adjacent Epitopes

2007 ◽  
Vol 81 (23) ◽  
pp. 12816-12826 ◽  
Author(s):  
Soila Sukupolvi-Petty ◽  
S. Kyle Austin ◽  
Whitney E. Purtha ◽  
Theodore Oliphant ◽  
Grant E. Nybakken ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Surface Display ◽  
Viral Envelope ◽  
Yeast Surface Display ◽  
Neutralizing Activity ◽  
Denv Serotypes ◽  
E Protein ◽  
Lateral Ridge ◽  
Domain Iii

ABSTRACT Neutralization of flaviviruses in vivo correlates with the development of an antibody response against the viral envelope (E) protein. Previous studies demonstrated that monoclonal antibodies (MAbs) against an epitope on the lateral ridge of domain III (DIII) of the West Nile virus (WNV) E protein strongly protect against infection in animals. Based on X-ray crystallography and sequence analysis, an analogous type-specific neutralizing epitope for individual serotypes of the related flavivirus dengue virus (DENV) was hypothesized. Using yeast surface display of DIII variants, we defined contact residues of a panel of type-specific, subcomplex-specific, and cross-reactive MAbs that recognize DIII of DENV type 2 (DENV-2) and have different neutralizing potentials. Type-specific MAbs with neutralizing activity against DENV-2 localized to a sequence-unique epitope on the lateral ridge of DIII, centered at the FG loop near residues E383 and P384, analogous in position to that observed with WNV-specific strongly neutralizing MAbs. Subcomplex-specific MAbs that bound some but not all DENV serotypes and neutralized DENV-2 infection recognized an adjacent epitope centered on the connecting A strand of DIII at residues K305, K307, and K310. In contrast, several MAbs that had poor neutralizing activity against DENV-2 and cross-reacted with all DENV serotypes and other flaviviruses recognized an epitope with residues in the AB loop of DIII, a conserved region that is predicted to have limited accessibility on the mature virion. Overall, our experiments define adjacent and structurally distinct epitopes on DIII of DENV-2 which elicit type-specific, subcomplex-specific, and cross-reactive antibodies with different neutralizing potentials.

scholarly journals Reduced sphingosine kinase 1 activity in dengue virus type-2 infected cells can be mediated by the 3′ untranslated region of dengue virus type-2 RNA

2013 ◽  
Vol 94 (11) ◽  
pp. 2437-2448 ◽  
Author(s):  
J. M. Carr ◽  
T. Kua ◽  
J. N. Clarke ◽  
J. K Calvert ◽  
J. R. Zebol ◽  
...  
Keyword(s):  
Cell Death ◽  
Dengue Virus ◽  
Virus Type ◽  
Elongation Factor ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
Diarrhea Virus ◽  
Infected Cells ◽  
Dengue Virus Type 2

Sphingosine kinase 1 (SphK1) is a lipid kinase with important roles including regulation of cell survival. We have previously shown reduced SphK1 activity in cells with an established dengue virus type-2 (DENV-2) infection. In this study, we examined the effect of alterations in SphK1 activity on DENV-2 replication and cell death and determined the mechanisms of the reduction in SphK1 activity. Chemical inhibition or overexpression of SphK1 after established DENV-2 infection had no effect on infectious DENV-2 production, although inhibition of SphK1 resulted in enhanced DENV-2-induced cell death. Reduced SphK1 activity was observed in multiple cell types, regardless of the ability of DENV-2 infection to be cytopathic, and was mediated by a post-translational mechanism. Unlike bovine viral diarrhea virus, where SphK1 activity is decreased by the NS3 protein, SphK1 activity was not affected by DENV-2 NS3 but, instead, was reduced by expression of the terminal 396 bases of the 3′ UTR of DENV-2 RNA. We have previously shown that eukaryotic elongation factor 1A (eEF1A) is a direct activator of SphK1 and here DENV-2 RNA co-localized and co-precipitated with eEF1A from infected cells. We propose that the reduction in SphK1 activity late in DENV-2-infected cells is a consequence of DENV-2 out-competing SphK1 for eEF1A binding and hijacking cellular eEF1A for its own replication strategy, rather than a specific host or virus-induced change in SphK1 to modulate viral replication. Nonetheless, reduced SphK1 activity may have important consequences for survival or death of the infected cell.

scholarly journals In VitroEvaluation of Antiprotozoal and Antiviral Activities of Extracts from ArgentineanMikaniaSpecies

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Laura C. Laurella ◽  
Fernanda M. Frank ◽  
Andrea Sarquiz ◽  
María R. Alonso ◽  
Gustavo Giberti ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Virus Type ◽  
Sesquiterpene Lactones ◽  
Infrared Analysis ◽  
Leishmania Braziliensis ◽  
Organic Extract ◽  
Chromatographic Profile ◽  
Antiviral Activities ◽  
Dengue Virus Type 2

The aim of this study was to investigate the antiprotozoal and antiviral activities of four ArgentineanMikaniaspecies. The organic and aqueous extracts ofMikania micrantha, M. parodii, M. periplocifolia,andM. cordifoliawere tested onTrypanosoma cruziepimastigotes,Leishmania braziliensispromastigotes, and dengue virus type 2. The organic extract ofM. micranthawas the most active againstT. cruziandL. braziliensisexhibiting a growth inhibition of77.6±4.5% and84.9±6.1%, respectively, at a concentration of 10 μg/ml. The bioguided fractionation ofM. micranthaorganic extract led to the identification of two active fractions. The chromatographic profile and infrared analysis of these fractions revealed the presence of sesquiterpene lactones. None of the tested extracts were active against dengue virus type 2.

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