Identification of B-Cell Epitope of Dengue Virus Type 1 and Its Application in Diagnosis of Patients

ABSTRACTCross-species transmission of simian foamy viruses (SFVs) from nonhuman primates (NHPs) to humans is currently ongoing. These zoonotic retroviruses establish lifelong persistent infection in their human hosts. SFV are apparently nonpathogenicin vivo, with ubiquitousin vitrotropism. Here, we aimed to identify envelope B-cell epitopes that are recognized following a zoonotic SFV infection. We screened a library of 169 peptides covering the external portion of the envelope from the prototype foamy virus (SFVpsc_huHSRV.13) for recognition by samples from 52 Central African hunters (16 uninfected and 36 infected with chimpanzee, gorilla, orCercopithecusSFV). We demonstrate the specific recognition of peptide N96-V110located in the leader peptide, gp18LP. Forty-three variant peptides with truncations, alanine substitutions, or amino acid changes found in other SFV species were tested. We mapped the epitope between positions 98 and 108 and defined six amino acids essential for recognition. Most plasma samples from SFV-infected humans cross-reacted with sequences from apes and Old World monkey SFV species. The magnitude of binding to peptide N96-V110was significantly higher for samples of individuals infected with a chimpanzee or gorilla SFV than those infected with aCercopithecusSFV. In conclusion, we have been the first to define an immunodominant B-cell epitope recognized by humans following zoonotic SFV infection.IMPORTANCEFoamy viruses are the oldest known retroviruses and have been mostly described to be nonpathogenic in their natural animal hosts. SFVs can be transmitted to humans, in whom they establish persistent infection, like the simian lenti- and deltaviruses that led to the emergence of two major human pathogens, human immunodeficiency virus type 1 and human T-lymphotropic virus type 1. This is the first identification of an SFV-specific B-cell epitope recognized by human plasma samples. The immunodominant epitope lies in gp18LP, probably at the base of the envelope trimers. The NHP species the most genetically related to humans transmitted SFV strains that induced the strongest antibody responses. Importantly, this epitope is well conserved across SFV species that infect African and Asian NHPs.

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Identification of a conserved neutralizing linear B-cell epitope in the VP1 proteins of duck hepatitis A virus type 1 and 3

Veterinary Microbiology ◽

10.1016/j.vetmic.2015.09.008 ◽

2015 ◽

Vol 180 (3-4) ◽

pp. 196-204 ◽

Cited By ~ 20

Author(s):

Ruihua Zhang ◽

Guomei Zhou ◽

Yinghao Xin ◽

Junhao Chen ◽

Shaoli Lin ◽

...

Keyword(s):

B Cell ◽

Virus Type ◽

Hepatitis A ◽

Hepatitis A Virus ◽

Cell Epitope ◽

Duck Hepatitis ◽

B Cell Epitope ◽

Linear B

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Identification of a dengue virus type 2 (DEN-2) serotype-specific B-cell epitope and detection of DEN-2-immunized animal serum samples using an epitope-based peptide antigen

Journal of General Virology ◽

10.1099/vir.0.19228-0 ◽

2003 ◽

Vol 84 (10) ◽

pp. 2771-2779 ◽

Cited By ~ 29

Author(s):

Han-Chung Wu ◽

Mei-Ying Jung ◽

Chien-Yu Chiu ◽

Ting-Ting Chao ◽

Szu-Chia Lai ◽

...

Keyword(s):

Dengue Virus ◽

B Cell ◽

Virus Type ◽

Synthetic Peptide ◽

Cell Epitope ◽

Serum Samples ◽

Peptide Antigen ◽

B Cell Epitope ◽

Dengue Virus Type 2

In this study, a serotype-specific monoclonal antibody (mAb), D2 16-1 (Ab4), against dengue virus type 2 (DEN-2) was generated. The specificity of Ab4, which recognized DEN-2 non-structural protein 1, was determined by ELISA, immunofluorescence and immunoblotting analyses. The serotype-specific B-cell epitope of Ab4 was identified further from a random phage-displayed peptide library; selected phage clones reacted specifically with Ab4 and did not react with other mAbs. Immunopositive phage clones displayed a consensus motif, His–Arg/Lys–Leu/Ile, and a synthetic peptide corresponding to the phage-displayed peptide bound specifically to Ab4. The His and Arg residues in this epitope were found to be crucial for peptide binding to Ab4 and binding activity decreased dramatically when these residues were changed to Leu. The epitope-based synthetic peptide not only identified serum samples from DEN-2-immunized mice and rabbits by ELISA but also differentiated clearly between serum samples from DEN-2- and Japanese encephalitis virus-immunized mice. This mAb and its epitope-based peptide antigen will be useful for serologic diagnosis of DEN-2 infection. Furthermore, DEN-2 epitope identification makes it feasible to dissect antibody responses to DEN and to address the role of antibodies in the pathogenesis of primary and secondary DEN-2 infections.

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The PEVKEK Region of the Pyridoxal Phosphate Binding Domain of GAD65 Expresses a Dominant B Cell Epitope for Type 1 Diabetes Sera

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.2002.tb02966.x ◽

2006 ◽

Vol 958 (1) ◽

pp. 182-189 ◽

Cited By ~ 6

Author(s):

JONATHAN C. TONG ◽

MARK A. MYERS ◽

IAN R. MACKAY ◽

PAUL Z. ZIMMET ◽

MERRILL J. ROWLEY

Keyword(s):

Type 1 Diabetes ◽

B Cell ◽

Pyridoxal Phosphate ◽

Cell Epitope ◽

Binding Domain ◽

Phosphate Binding ◽

B Cell Epitope

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Comprehensive mapping of immunodominant and conserved serotype- and group-specific B-cell epitopes of nonstructural protein 1 from dengue virus type 1

Virology ◽

10.1016/j.virol.2009.12.010 ◽

2010 ◽

Vol 398 (2) ◽

pp. 290-298 ◽

Cited By ~ 23

Author(s):

Yue Chen ◽

Yuxian Pan ◽

Yonghui Guo ◽

Liwen Qiu ◽

Xixia Ding ◽

...

Keyword(s):

Dengue Virus ◽

B Cell ◽

Virus Type ◽

Nonstructural Protein ◽

B Cell Epitopes ◽

Nonstructural Protein 1 ◽

Comprehensive Mapping

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Identification and characterization of a linearized B-cell epitope on the pr protein of dengue virus

Journal of General Virology ◽

10.1099/vir.0.052084-0 ◽

2013 ◽

Vol 94 (7) ◽

pp. 1510-1516 ◽

Cited By ~ 5

Author(s):

Ke-Yu Song ◽

Hui Zhao ◽

Shi-Hua Li ◽

Xiao-Feng Li ◽

Yong-Qiang Deng ◽

...

Keyword(s):

Dengue Virus ◽

B Cell ◽

Cell Epitope ◽

Denv Infection ◽

Site Directed Mutagenesis ◽

B Cell Epitopes ◽

Virion Assembly ◽

Pr Protein ◽

B Cell Epitope ◽

Hyperimmune Antiserum

The four serotypes of dengue virus (DENV) represent one of the major mosquito-borne pathogens globally; so far no vaccine or specific antiviral is available. During virion maturation, the pr protein is cleaved from its precursor form the prM protein on the surface of immature DENV by host protease. Recent findings have demonstrated that the pr protein not only played critical roles in virion assembly and maturation, but was also involved in antibody-dependent enhancement of DENV infection. However, the B-cell epitopes on the pr protein of DENV have not been well characterized. In this study, a set of 11 partially overlapping peptides spanning the entire pr protein of DENV-2 were fused with glutathione S-transferase and expressed in Escherichia coli. ELISA screening with murine hyperimmune antiserum against immature DENV identified the P8 peptide (57KQNEPEDIDCWCNST71) in the pr protein as the major immunodominant epitope. Fine mapping by truncated protein assays confirmed the 8-e peptide 57KQNEPEDI64 was the smallest unit capable of antibody binding. Importantly, the 8-e epitope reacted with sera from dengue fever patients. Site-directed mutagenesis revealed the asparagine residue at position 59 was important for epitope recognition. The 8-e epitope coincided well with the B-cell epitopes predicted by Immune Epitope Database analysis, and 3D structural modelling mapped the 8-e peptide on the surface of prM-E heterodimers. Overall, our findings characterized a linearized B-cell epitope on the pr protein of DENV, which will help to understand the life cycle of DENV and pathogenesis of dengue infections in human.

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Construction of a novel vaccine by conjugating a B-cell epitope of DPP4 to peptide IA2(5)-P2-1 to significantly control type 1 diabetes in NOD mice

Vaccine ◽

10.1016/j.vaccine.2017.10.035 ◽

2017 ◽

Vol 35 (51) ◽

pp. 7187-7197 ◽

Cited By ~ 1

Author(s):

Ya Li ◽

Huimin Cao ◽

Yiping Li ◽

Zhixin Li ◽

Xiaomin Wei ◽

...

Keyword(s):

Type 1 Diabetes ◽

B Cell ◽

Cell Epitope ◽

Nod Mice ◽

B Cell Epitope

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Identification of a Type-Specific Epitope in the ORF2 Protein of Duck Astrovirus Type 1

Animals ◽

10.3390/ani9121069 ◽

2019 ◽

Vol 9 (12) ◽

pp. 1069 ◽

Cited By ~ 2

Author(s):

Lan ◽

Zhang ◽

Li ◽

Chen ◽

Xie ◽

...

Keyword(s):

B Cell ◽

Cell Epitope ◽

Cross Reactivity ◽

Protein Sequence Analysis ◽

Dot Blot ◽

Reading Frame ◽

B Cell Epitope ◽

Orf2 Protein ◽

Linear B

Duck astrovirus type 1 (DAstV-1) infection constitutes a cause of viral hepatitis in ducklings and little is known about the B-cell epitope of DAstV-1. In this study, a monoclonal antibody (mAb) 3D2 against open reading frame 2 (ORF2) protein of DAstV-1 was used to identify the possible epitope in the four serotypes of DAstV. The mAb 3D2 showed no neutralization activity to DAstV-1, and reacted with the conserved linear B-cell epitopes of 454STTESA459 in DAstV-1 ORF2 protein. Sequence analysis, dot blot assay, and cross-reactivity test indicated that the epitope peptide was highly conserved in DAstV-1 sequence and mAb 3D2 had no cross-reactivity with other DAstV serotypes. To the best of our knowledge, this is the first report about identification of the specific conserved linear B-cell epitope of DAstV-1, which will facilitate the serologic diagnosis of DAstV-1 infection.

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