title: Extensive complement-dependent enhancement of HIV-1 by autologous non-neutralising antibodies at early stages of infection.
abstract: BACKGROUND
  Non-neutralising antibodies to the envelope glycoprotein are elicited during acute HIV-1 infection and are abundant throughout the course of disease progression. Although these antibodies appear to have negligible effects on HIV-1 infection when assayed in standard neutralisation assays, they have the potential to exert either inhibitory or enhancing effects through interactions with complement and/or Fc receptors. Here we report that non-neutralising antibodies produced early in response to HIV-1 infection can enhance viral infectivity.
  
  
  RESULTS
  We investigated this complement-mediated antibody-dependent enhancement (C'-ADE) of early HIV infection by carrying out longitudinal studies with primary viruses and autologous sera derived sequentially from recently infected individuals, using a T cell line naturally expressing the complement receptor 2 (CR2; CD21). The C'-ADE was consistently observed and in some cases achieved infection-enhancing levels of greater than 350-fold, converting a low-level infection to a highly destructive one. C'-ADE activity declined as a neutralising response to the early virus emerged, but later virus isolates that had escaped the neutralising response demonstrated an increased capacity for enhanced infection by autologous antibodies. Moreover, sera with autologous enhancing activity were capable of C'ADE of heterologous viral isolates, suggesting the targeting of conserved epitopes on the envelope glycoprotein. Ectopic expression of CR2 on cell lines expressing HIV-1 receptors was sufficient to render them sensitive to C'ADE.
  
  
  CONCLUSIONS
  Taken together, these results suggest that non-neutralising antibodies to the HIV-1 envelope that arise during acute infection are not 'passive', but in concert with complement and complement receptors may have consequences for HIV-1 dissemination and pathogenesis.
authors.affiliation: Division of Infection and Immunity, University College London, MRC/UCL Centre for Medical Molecular Virology, 46 Cleveland Street, London W1T 4JF, UK.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Willey
authors.forename: Marlén M I
authors.initials: MM
authors.lastname: Aasa-Chapman
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Farrell
authors.forename: Pierre
authors.initials: P
authors.lastname: Pellegrino
authors.forename: Ian
authors.initials: I
authors.lastname: Williams
authors.forename: Robin A
authors.initials: RA
authors.lastname: Weiss
authors.forename: Stuart J D
authors.initials: SJ
authors.lastname: Neil
mesh_terms: D057134:Antibodies, Neutralizing / Q000097:blood* / Q000276:immunology; D019067:Antibody-Dependent Enhancement; D002460:Cell Line; D003167:Complement Activation; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism*; D015483:HIV Antibodies / Q000097:blood* / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009500:Neutralization Tests; D017464:Receptors, Complement 3d / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D017464:Receptors, Complement 3d; D003165:Complement System Proteins