Discrete partitioning of HIV-1 Env forms revealed by viral capture

• DOI: 10.1186/s12977-015-0207-z
• Publication Date: 2015-09-24T00:50:19Z
• Authors: Daniel J. Stieh; Deborah F. King; Katja Klein; Yoann Aldon; Paul F. McKay; Robin J. Shattock
• Keywords: Monoclonal antibody; 0301 basic medicine; Envelope glycoprotein; HIV Antibodies; HIV Envelope Protein gp120; HIV Envelope Protein gp160; 03 medical and health sciences; Virology; Humans; Immunoassay; Science & Technology; Research; Neutralizing anitboides; Virion; Antibodies, Monoclonal; Viral heterogeneity; Poten neutralization; Antibodies, Neutralizing; HIV Envelope Protein gp41; 3. Good health; Infectious Diseases; HIV-1; Nonneutralizing antibodies; Life Sciences & Biomedicine; Protein Binding

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.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.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.