دورية أكاديمية
Natural strain variation and antibody neutralization of dengue serotype 3 viruses.
| العنوان: | Natural strain variation and antibody neutralization of dengue serotype 3 viruses. |
|---|---|
| المؤلفون: | Wahala WM; Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America., Donaldson EF, de Alwis R, Accavitti-Loper MA, Baric RS, de Silva AM |
| المصدر: | PLoS pathogens [PLoS Pathog] 2010 Mar 19; Vol. 6 (3), pp. e1000821. Date of Electronic Publication: 2010 Mar 19. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: Electronic Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: San Francisco, CA : Public Library of Science, c2005- |
| مواضيع طبية MeSH: | Antibodies, Monoclonal/*immunology , Antibodies, Monoclonal/*pharmacology , Dengue/*immunology , Dengue/*virology , Dengue Virus/*genetics , Dengue Virus/*immunology, Aedes/cytology ; Animals ; Antibodies, Monoclonal/metabolism ; Chlorocebus aethiops ; Dengue Virus/classification ; Epitope Mapping ; Epitopes/immunology ; Genotype ; Humans ; Mice ; Mutagenesis, Site-Directed ; Neutralization Tests ; Protein Binding/immunology ; U937 Cells ; Vero Cells ; Viral Proteins/genetics ; Viral Proteins/immunology |
| مستخلص: | Dengue viruses (DENVs) are emerging, mosquito-borne flaviviruses which cause dengue fever and dengue hemorrhagic fever. The DENV complex consists of 4 serotypes designated DENV1-DENV4. Following natural infection with DENV, individuals develop serotype specific, neutralizing antibody responses. Monoclonal antibodies (MAbs) have been used to map neutralizing epitopes on dengue and other flaviviruses. Most serotype-specific, neutralizing MAbs bind to the lateral ridge of domain III of E protein (EDIII). It has been widely assumed that the EDIII lateral ridge epitope is conserved within each DENV serotype and a good target for vaccines. Using phylogenetic methods, we compared the amino acid sequence of 175 E proteins representing the different genotypes of DENV3 and identified a panel of surface exposed amino acids, including residues in EDIII, that are highly variant across the four DENV3 genotypes. The variable amino acids include six residues at the lateral ridge of EDIII. We used a panel of DENV3 mouse MAbs to assess the functional significance of naturally occurring amino acid variation. From the panel of antibodies, we identified three neutralizing MAbs that bound to EDIII of DENV3. Recombinant proteins and naturally occurring variant viruses were used to map the binding sites of the three MAbs. The three MAbs bound to overlapping but distinct epitopes on EDIII. Our empirical studies clearly demonstrate that the antibody binding and neutralization capacity of two MAbs was strongly influenced by naturally occurring mutations in DENV3. Our data demonstrate that the lateral ridge "type specific" epitope is not conserved between strains of DENV3. This variability should be considered when designing and evaluating DENV vaccines, especially those targeting EDIII. |
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| معلومات مُعتمدة: | U54 AI057157 United States AI NIAID NIH HHS |
| المشرفين على المادة: | 0 (Antibodies, Monoclonal) 0 (Epitopes) 0 (Viral Proteins) |
| تواريخ الأحداث: | Date Created: 20100325 Date Completed: 20100624 Latest Revision: 20211020 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC2841629 |
| DOI: | 10.1371/journal.ppat.1000821 |
| PMID: | 20333252 |
| قاعدة البيانات: | MEDLINE |
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