title: Discrete partitioning of HIV-1 Env forms revealed by viral capture.
abstract: 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.
authors.affiliation: Department of Cellular and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA. dstieh@northwestern.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Stieh
authors.affiliation: Mucosal Infection and Immunity Group, Section of Infectious Diseases, Imperial College London, St Mary's Campus, London, W2 1PG, UK. d.king@imperial.ac.uk.
authors.forename: Deborah F
authors.initials: DF
authors.lastname: King
authors.affiliation: Mucosal Infection and Immunity Group, Section of Infectious Diseases, Imperial College London, St Mary's Campus, London, W2 1PG, UK. kklein5@uwo.ca.
authors.forename: Katja
authors.initials: K
authors.lastname: Klein
authors.affiliation: Mucosal Infection and Immunity Group, Section of Infectious Diseases, Imperial College London, St Mary's Campus, London, W2 1PG, UK. y.aldon@imperial.ac.uk.
authors.forename: Yoann
authors.initials: Y
authors.lastname: Aldon
authors.affiliation: Mucosal Infection and Immunity Group, Section of Infectious Diseases, Imperial College London, St Mary's Campus, London, W2 1PG, UK. p.mckay@imperial.ac.uk.
authors.forename: Paul F
authors.initials: PF
authors.lastname: McKay
authors.affiliation: Mucosal Infection and Immunity Group, Section of Infectious Diseases, Imperial College London, St Mary's Campus, London, W2 1PG, UK. r.shattock@imperial.ac.uk.
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Shattock
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D019302:HIV Envelope Protein gp160 / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology / Q000502:physiology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007118:Immunoassay; D011485:Protein Binding; D014771:Virion / Q000276:immunology / Q000302:isolation & purification* / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41