Cargando…
Extensive complement-dependent enhancement of HIV-1 by autologous non-neutralising antibodies at early stages of infection
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,...
Autores principales: | , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065417/ https://www.ncbi.nlm.nih.gov/pubmed/21401915 http://dx.doi.org/10.1186/1742-4690-8-16 |
_version_ | 1782200976941252608 |
---|---|
author | Willey, Suzanne Aasa-Chapman, Marlén MI O'Farrell, Stephen Pellegrino, Pierre Williams, Ian Weiss, Robin A Neil, Stuart JD |
author_facet | Willey, Suzanne Aasa-Chapman, Marlén MI O'Farrell, Stephen Pellegrino, Pierre Williams, Ian Weiss, Robin A Neil, Stuart JD |
author_sort | Willey, Suzanne |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-3065417 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-30654172011-03-29 Extensive complement-dependent enhancement of HIV-1 by autologous non-neutralising antibodies at early stages of infection Willey, Suzanne Aasa-Chapman, Marlén MI O'Farrell, Stephen Pellegrino, Pierre Williams, Ian Weiss, Robin A Neil, Stuart JD Retrovirology Research 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. BioMed Central 2011-03-14 /pmc/articles/PMC3065417/ /pubmed/21401915 http://dx.doi.org/10.1186/1742-4690-8-16 Text en Copyright ©2011 Willey et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Willey, Suzanne Aasa-Chapman, Marlén MI O'Farrell, Stephen Pellegrino, Pierre Williams, Ian Weiss, Robin A Neil, Stuart JD Extensive complement-dependent enhancement of HIV-1 by autologous non-neutralising antibodies at early stages of infection |
title | Extensive complement-dependent enhancement of HIV-1 by autologous non-neutralising antibodies at early stages of infection |
title_full | Extensive complement-dependent enhancement of HIV-1 by autologous non-neutralising antibodies at early stages of infection |
title_fullStr | Extensive complement-dependent enhancement of HIV-1 by autologous non-neutralising antibodies at early stages of infection |
title_full_unstemmed | Extensive complement-dependent enhancement of HIV-1 by autologous non-neutralising antibodies at early stages of infection |
title_short | Extensive complement-dependent enhancement of HIV-1 by autologous non-neutralising antibodies at early stages of infection |
title_sort | extensive complement-dependent enhancement of hiv-1 by autologous non-neutralising antibodies at early stages of infection |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065417/ https://www.ncbi.nlm.nih.gov/pubmed/21401915 http://dx.doi.org/10.1186/1742-4690-8-16 |
work_keys_str_mv | AT willeysuzanne extensivecomplementdependentenhancementofhiv1byautologousnonneutralisingantibodiesatearlystagesofinfection AT aasachapmanmarlenmi extensivecomplementdependentenhancementofhiv1byautologousnonneutralisingantibodiesatearlystagesofinfection AT ofarrellstephen extensivecomplementdependentenhancementofhiv1byautologousnonneutralisingantibodiesatearlystagesofinfection AT pellegrinopierre extensivecomplementdependentenhancementofhiv1byautologousnonneutralisingantibodiesatearlystagesofinfection AT williamsian extensivecomplementdependentenhancementofhiv1byautologousnonneutralisingantibodiesatearlystagesofinfection AT weissrobina extensivecomplementdependentenhancementofhiv1byautologousnonneutralisingantibodiesatearlystagesofinfection AT neilstuartjd extensivecomplementdependentenhancementofhiv1byautologousnonneutralisingantibodiesatearlystagesofinfection |