Thymic HIV-2 infection uncovers posttranscriptional control of viral replication in human thymocytes

Detalhes bibliográficos
Autor(a) principal: Nunes-Cabaço, H.
Data de Publicação: 2015
Outros Autores: Matoso, P., Foxall, R. B., Tendeiro, R., Pires, A. R., Carvalho, Tânia, Pinheiro, A. I., Soares, R. S., Sousa, A. E.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/18447
Resumo: © 2015, American Society for Microbiology. All Rights Reserved.
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spelling Thymic HIV-2 infection uncovers posttranscriptional control of viral replication in human thymocytes© 2015, American Society for Microbiology. All Rights Reserved.A unique HIV-host equilibrium exists in untreated HIV-2-infected individuals. This equilibrium is characterized by low to undetectable levels of viremia throughout the disease course, despite the establishment of disseminated HIV-2 reservoirs at levels comparable to those observed in untreated HIV-1 infection. Although the clinical spectrum is similar in the two infections, HIV-2 infection is associated with a much lower rate of CD4 T-cell decline and has a limited impact on the mortality of infected adults. Here we investigated HIV-2 infection of the human thymus, the primary organ for T-cell production. Human thymic tissue and suspensions of total or purified CD4 single-positive thymocytes were infected with HIV-2 or HIV-1 primary isolates using either CCR5 or CXCR4 coreceptors. We found that HIV-2 infected both thymic organ cultures and thymocyte suspensions, as attested to by the total HIV DNA and cell-associated viral mRNA levels. Nevertheless, thymocytes featured reduced levels of intracellular Gag viral protein, irrespective of HIV-2 coreceptor tropism and cell differentiation stage, in agreement with the low viral load in culture supernatants. Our data show that HIV-2 is able to infect the human thymus, but the HIV-2 replication cycle in thymocytes is impaired, providing a new model to identify therapeutic targets for viral replication control. IMPORTANCE: HIV-1 infects the thymus, leading to a decrease in CD4 T-cell production that contributes to the characteristic CD4 T-cell loss. HIV-2 infection is associated with a very low rate of progression to AIDS and is therefore considered a unique naturally occurring model of attenuated HIV disease. HIV-2-infected individuals feature low to undetectable plasma viral loads, in spite of the numbers of circulating infected T cells being similar to those found in patients infected with HIV-1. We assessed, for the first time, the direct impact of HIV-2 infection on the human thymus. We show that HIV-2 is able to infect the thymus but that the HIV-2 replication cycle in thymocytes is impaired. We propose that this system will be important to devise immunotherapies that target viral production, aiding the design of future therapeutic strategies for HIV control.This work was supported by the Fundação para a Ciência e a Tecnologia (FCT) and by the Programa Operacional Ciência e Inovação 2010 (POCI2010), grant PTDC/SAU-MII/66248/2006 to A.E.S. H.N.-C., R.B.F., R.T., and R.S.S. received scholarships from FCT cofinanced by POCI2010.American Society for MicrobiologyRepositório da Universidade de LisboaNunes-Cabaço, H.Matoso, P.Foxall, R. B.Tendeiro, R.Pires, A. R.Carvalho, TâniaPinheiro, A. I.Soares, R. S.Sousa, A. E.2015-07-14T15:37:19Z20152015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/18447engJournal of Virology February 2015 Volume 89 Number 40022-538Xhttp://dx.doi.org/ 10.1128/JVI.03047-14info: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:RCAAP2023-11-08T16:04:43Zoai:repositorio.ul.pt:10451/18447Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:37:59.218956Repositório 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 Thymic HIV-2 infection uncovers posttranscriptional control of viral replication in human thymocytes
title Thymic HIV-2 infection uncovers posttranscriptional control of viral replication in human thymocytes
spellingShingle Thymic HIV-2 infection uncovers posttranscriptional control of viral replication in human thymocytes
Nunes-Cabaço, H.
title_short Thymic HIV-2 infection uncovers posttranscriptional control of viral replication in human thymocytes
title_full Thymic HIV-2 infection uncovers posttranscriptional control of viral replication in human thymocytes
title_fullStr Thymic HIV-2 infection uncovers posttranscriptional control of viral replication in human thymocytes
title_full_unstemmed Thymic HIV-2 infection uncovers posttranscriptional control of viral replication in human thymocytes
title_sort Thymic HIV-2 infection uncovers posttranscriptional control of viral replication in human thymocytes
author Nunes-Cabaço, H.
author_facet Nunes-Cabaço, H.
Matoso, P.
Foxall, R. B.
Tendeiro, R.
Pires, A. R.
Carvalho, Tânia
Pinheiro, A. I.
Soares, R. S.
Sousa, A. E.
author_role author
author2 Matoso, P.
Foxall, R. B.
Tendeiro, R.
Pires, A. R.
Carvalho, Tânia
Pinheiro, A. I.
Soares, R. S.
Sousa, A. E.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Nunes-Cabaço, H.
Matoso, P.
Foxall, R. B.
Tendeiro, R.
Pires, A. R.
Carvalho, Tânia
Pinheiro, A. I.
Soares, R. S.
Sousa, A. E.
description © 2015, American Society for Microbiology. All Rights Reserved.
publishDate 2015
dc.date.none.fl_str_mv 2015-07-14T15:37:19Z
2015
2015-01-01T00:00:00Z
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/10451/18447
url http://hdl.handle.net/10451/18447
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Journal of Virology February 2015 Volume 89 Number 4
0022-538X
http://dx.doi.org/ 10.1128/JVI.03047-14
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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