Discrete partitioning of HIV-1 Env forms revealed by viral capture
| Autor: | Deborah King, Yoann Aldon, Daniel J. Stieh, Paul F. McKay, Robin J. Shattock, Katja Klein |
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| Rok vydání: | 2015 |
| Předmět: |
Monoclonal antibody
medicine.drug_class viruses Heterologous Envelope glycoprotein Plasma protein binding HIV Antibodies HIV Envelope Protein gp120 Biology Gp41 Neutralization HIV Envelope Protein gp160 03 medical and health sciences Virology medicine Humans 030304 developmental biology Immunoassay chemistry.chemical_classification Infectivity 0303 health sciences Science & Technology Research Neutralizing anitboides 030302 biochemistry & molecular biology Virion Antibodies Monoclonal virus diseases Viral heterogeneity Poten neutralization Antibodies Neutralizing HIV Envelope Protein gp41 3. Good health Infectious Diseases chemistry HIV-1 biology.protein Antibody Nonneutralizing antibodies Glycoprotein Life Sciences & Biomedicine Protein Binding |
| Zdroj: | Retrovirology |
| ISSN: | 1742-4690 |
| DOI: | 10.1186/s12977-015-0207-z |
| Popis: | Background The structure of HIV-1 envelope glycoprotein (Env) is flexible and heterogeneous on whole virions. Although functional Env complexes are thought to require trimerization of cleaved gp41/gp120 heterodimers, variable processing can result in the potential incorporation of non-functional uncleaved proteins (gp160), non-trimeric arrangements of gp41/gp120 heterodimers, and gp120 depleted gp41 stumps. The potential distribution of functional and non-functional Env forms across replication-competent viral populations may have important implications for neutralizing and non-neutralizing antibody functions. This study applied an immuno-bead viral capture assay (VCA) to interrogate the potential distribution (heterologous vs homologous) of functional and non-functional forms of virion associated Env. Results The VCA revealed a significant association between depletion of infectious virions and virion Env incorporation, but not between infectivity and p24-gag. Three distinct subpopulations of virions were identified within pools of genetically homogenous viral particles. Critically, a significant subpopulation of infectious virions were exclusively captured by neutralizing antibodies (nAbs) indicative of a homologous distribution of functional trimeric Env forms. A second infectious subpopulation bound both neutralizing and non-neutralizing antibodies (nnAbs) representative of a heterologous distribution of Env forms, while a third non-infectious subpopulation was predominantly bound by nnAbs recognizing gp41 stumps. Conclusions The observation that a distinct and significant subpopulation of infectious virions is exclusively captured by neutralizing antibodies has important implications for understanding antibody binding and neutralization, as well as other antibody effector functions. Electronic supplementary material The online version of this article (doi:10.1186/s12977-015-0207-z) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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