Resistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropism

Detalhes bibliográficos
Autor(a) principal: Marcelino, José Maria
Data de Publicação: 2012
Outros Autores: Borrego, Pedro, Nilsson, Charlotta, Família, Carlos, Barroso, Helena, Maltez, Fernando, Doroana, Manuela, Antunes, Francisco, Quintas, Alexandre, Taveira, Nuno
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.26/4941
Resumo: This is a non-final version of an article published in final form in AIDS. 28 November 2012 - Volume 26 - Issue 18 - p 2275–2284
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spelling Resistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropismHIV-2X4 TropismAntibody neutralizationThis is a non-final version of an article published in final form in AIDS. 28 November 2012 - Volume 26 - Issue 18 - p 2275–2284Objectives: To characterize the nature and dynamics of the neutralizing antibody (NAb) response and escape in chronically HIV-2 infected patients.Methods: Twenty-eight chronically infected adults were studied over a period of 1-4 years. The neutralizing activity of plasma IgG antibodies against autologous and heterologous primary isolates was analyzed using a standard assay in TZM-bl cells. Coreceptor usage was determined in GHOST cells. The sequence and predicted 3Dstructure of the C2V3C3 Env region were determined for all isolates.Results: Only 50% of the patients consistently produced IgG NAbs to autologous and contemporaneous virus isolates. In contrast, 96% of the patients produced IgG antibodies that neutralized at least two isolates of a panel of six heterologous R5 isolates. Breadth and potency of the neutralizing antibodies were positively associated with the number of CD4+ T cells and with the titer and avidity of C2V3C3-specific binding IgG antibodies. X4 isolates were obtained only from late stage disease patients and were fully resistant to neutralization. The V3 loop of X4 viruses was longer, had a higher net charge and differed markedly in secondary structure compared to R5 viruses.Conclusions: Most HIV-2 patients infected with R5 isolates produce C2V3C3-specific neutralizing antibodies whose potency and breadth decreases as the disease progresses. Resistance to antibody neutralization occurs in late stage disease and is usually associated with X4 viral tropism and major changes in V3 sequence and conformation. Our studies support a model of HIV-2 pathogenesis in which the neutralizing antibodies play a central role and have clear implications for the vaccine field.Fundação para a Ciência e Tecnologia, PortugalLippincott Williams & WilkinsRepositório ComumMarcelino, José MariaBorrego, PedroNilsson, CharlottaFamília, CarlosBarroso, HelenaMaltez, FernandoDoroana, ManuelaAntunes, FranciscoQuintas, AlexandreTaveira, Nuno2013-11-25T09:54:53Z2012-11-28T00:00:00Z2012-11-28T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.26/4941engAIDS. 28 November 2012 - Volume 26 - Issue 18 - p 2275–2284doi: 10.1097/QAD.0b013e328359a89dinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-10-06T14:51:24Zoai:comum.rcaap.pt:10400.26/4941Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T15:06:01.120723Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Resistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropism
title Resistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropism
spellingShingle Resistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropism
Marcelino, José Maria
HIV-2
X4 Tropism
Antibody neutralization
title_short Resistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropism
title_full Resistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropism
title_fullStr Resistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropism
title_full_unstemmed Resistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropism
title_sort Resistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropism
author Marcelino, José Maria
author_facet Marcelino, José Maria
Borrego, Pedro
Nilsson, Charlotta
Família, Carlos
Barroso, Helena
Maltez, Fernando
Doroana, Manuela
Antunes, Francisco
Quintas, Alexandre
Taveira, Nuno
author_role author
author2 Borrego, Pedro
Nilsson, Charlotta
Família, Carlos
Barroso, Helena
Maltez, Fernando
Doroana, Manuela
Antunes, Francisco
Quintas, Alexandre
Taveira, Nuno
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Comum
dc.contributor.author.fl_str_mv Marcelino, José Maria
Borrego, Pedro
Nilsson, Charlotta
Família, Carlos
Barroso, Helena
Maltez, Fernando
Doroana, Manuela
Antunes, Francisco
Quintas, Alexandre
Taveira, Nuno
dc.subject.por.fl_str_mv HIV-2
X4 Tropism
Antibody neutralization
topic HIV-2
X4 Tropism
Antibody neutralization
description This is a non-final version of an article published in final form in AIDS. 28 November 2012 - Volume 26 - Issue 18 - p 2275–2284
publishDate 2012
dc.date.none.fl_str_mv 2012-11-28T00:00:00Z
2012-11-28T00:00:00Z
2013-11-25T09:54:53Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.26/4941
url http://hdl.handle.net/10400.26/4941
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv AIDS. 28 November 2012 - Volume 26 - Issue 18 - p 2275–2284
doi: 10.1097/QAD.0b013e328359a89d
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv Lippincott Williams & Wilkins
publisher.none.fl_str_mv Lippincott Williams & Wilkins
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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