Increased expression of CDKN1A/p21 in HIV-1 controllers is correlated with upregulation of ZC3H12A/MCPIP1
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2020 |
| Outros Autores: | , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| DOI: | 10.1186/s12977-020-00522-4 |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/43100 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS & Imunologia Molecular. Rio de Janeiro, RJ, Brasil. |
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Azevedo, Suwellen S. D.Ribeiro-Alves, MarceloCôrtes, Fernanda H.Delatorre, EdsonSpangenberg, LuciaNaya, HugoSeito, Leonardo N.Hoagland, BrendaGrinsztejn, BeatrizVeloso, Valdiléa G.Morgado, Mariza G.Souza, Thiago Moreno L.Bello, Gonzalo2020-08-31T23:58:05Z2020-08-31T23:58:05Z2020Azevedo, Suwellen S. D. et al. Increased expression of CDKN1A/p21 in HIV-1 controllers is correlated with upregulation of ZC3H12A/MCPIP1. Retrovirology, v. 17, n. 1, p. 1-14, 2020.1742-4690https://www.arca.fiocruz.br/handle/icict/4310010.1186/s12977-020-00522-4engBMCIncreased expression of CDKN1A/p21 in HIV-1 controllers is correlated with upregulation of ZC3H12A/MCPIP1info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS & Imunologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS & Imunologia Molecular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Espírito Santo. Centro de Ciências Exatas, Naturais e da Saúde. Departamento de Biologia. Alegre, ES, Brasil.Institut Pasteur Montevideo. Unidad de Bioinformática. Montevideo, Uruguay / Universidad Católica del Uruguay. Facultad de Ingeniería y Tecnologías. Departamento de Informática y Ciencias de la Computación. Montevideo, Uruguay.Institut Pasteur Montevideo. Unidad de Bioinformática. Montevideo, Uruguay / Universidad de la República. Facultad de Agronomía. Departamento de Producción Animal y Pasturas. Montevideo, Uruguay.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos-Farmanguinhos. Laboratório de Farmacologia Aplicada. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS & Imunologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Inovação em Doenças de Populações Negligenciadas. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS & Imunologia Molecular. Rio de Janeiro, RJ, Brasil.Background: Some multifunctional cellular proteins, as the monocyte chemotactic protein-induced protein 1 (ZC3H12A/MCPIP1) and the cyclin-dependent kinase inhibitor CDKN1A/p21, are able to modulate the cellular susceptibility to the human immunodeficiency virus type 1 (HIV-1). Several studies showed that CDKN1A/p21 is expressed at high levels ex vivo in cells from individuals who naturally control HIV-1 replication (HIC) and a recent study supports a coordinate regulation of ZC3H12A/MCPIP1 and CDKN1A/p21 transcripts in a model of renal carcinoma cells. Here, we explored the potential associations between mRNA expression of ZC3H12A/MCPIP1 and CDKN1A/p21 in HIC sustaining undetectable (elite controllers-EC) or low (viremic controllers-VC) viral loads. Results: We found a selective upregulation of ZC3H12A/MCPIP1 and CDKN1A/p21 mRNA levels in PBMC from HIC compared with both ART-suppressed and HIV-negative control groups (P≤ 0.02) and higher MCPIP1 and p21 proteins levels in HIC than in HIV-1 negative subjects. There was a moderate positive correlation (r ≥ 0.57; P ≤ 0.014) between expressions of both transcripts in HIC and in HIC combined with control groups. We found positive correlations between the mRNA level of CDKN1A/p21 with activated CD4+ T cells levels in HIC (r ≥ 0.53; P ≤ 0.017) and between the mRNA levels of both CDKN1A/p21 (r = 0.74; P = 0.005) and ZC3H12A/MCPIP1 (r = 0.58; P = 0.040) with plasmatic levels of sCD14 in EC. Reanalysis of published transcriptomic data confirmed the positive association between ZC3H12A/MCPIP1 and CDKN1A/p21 mRNA levels in CD4+ T cells and monocytes from disparate cohorts of HIC and other HIV-positive control groups. Conclusions: These data show for the first time the simultaneous upregulation of ZC3H12A/MCPIP1 and CDKN1A/p21 transcripts in the setting of natural suppression of HIV-1 replication in vivo and the positive correlation of the expression of these cellular factors in disparate cohorts of HIV-positive individuals. The existence of a common regulatory pathway connecting ZC3H12A/MCPIP1 and CDKN1A/p21 could have a synergistic effect on HIV-1 replication control and pharmacological manipulation of these multifunctional host factors may open novel therapeutic perspectives to prevent HIV-1 replication and disease progression.HIV-1 controllersImmune activationMCPIP1Restriction factorsp21info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; 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| dc.title.pt_BR.fl_str_mv |
Increased expression of CDKN1A/p21 in HIV-1 controllers is correlated with upregulation of ZC3H12A/MCPIP1 |
| title |
Increased expression of CDKN1A/p21 in HIV-1 controllers is correlated with upregulation of ZC3H12A/MCPIP1 |
| spellingShingle |
Increased expression of CDKN1A/p21 in HIV-1 controllers is correlated with upregulation of ZC3H12A/MCPIP1 Azevedo, Suwellen S. D. HIV-1 controllers Immune activation MCPIP1 Restriction factors p21 |
| title_short |
Increased expression of CDKN1A/p21 in HIV-1 controllers is correlated with upregulation of ZC3H12A/MCPIP1 |
| title_full |
Increased expression of CDKN1A/p21 in HIV-1 controllers is correlated with upregulation of ZC3H12A/MCPIP1 |
| title_fullStr |
Increased expression of CDKN1A/p21 in HIV-1 controllers is correlated with upregulation of ZC3H12A/MCPIP1 |
| title_full_unstemmed |
Increased expression of CDKN1A/p21 in HIV-1 controllers is correlated with upregulation of ZC3H12A/MCPIP1 |
| title_sort |
Increased expression of CDKN1A/p21 in HIV-1 controllers is correlated with upregulation of ZC3H12A/MCPIP1 |
| author |
Azevedo, Suwellen S. D. |
| author_facet |
Azevedo, Suwellen S. D. Ribeiro-Alves, Marcelo Côrtes, Fernanda H. Delatorre, Edson Spangenberg, Lucia Naya, Hugo Seito, Leonardo N. Hoagland, Brenda Grinsztejn, Beatriz Veloso, Valdiléa G. Morgado, Mariza G. Souza, Thiago Moreno L. Bello, Gonzalo |
| author_role |
author |
| author2 |
Ribeiro-Alves, Marcelo Côrtes, Fernanda H. Delatorre, Edson Spangenberg, Lucia Naya, Hugo Seito, Leonardo N. Hoagland, Brenda Grinsztejn, Beatriz Veloso, Valdiléa G. Morgado, Mariza G. Souza, Thiago Moreno L. Bello, Gonzalo |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Azevedo, Suwellen S. D. Ribeiro-Alves, Marcelo Côrtes, Fernanda H. Delatorre, Edson Spangenberg, Lucia Naya, Hugo Seito, Leonardo N. Hoagland, Brenda Grinsztejn, Beatriz Veloso, Valdiléa G. Morgado, Mariza G. Souza, Thiago Moreno L. Bello, Gonzalo |
| dc.subject.en.pt_BR.fl_str_mv |
HIV-1 controllers Immune activation MCPIP1 Restriction factors p21 |
| topic |
HIV-1 controllers Immune activation MCPIP1 Restriction factors p21 |
| description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS & Imunologia Molecular. Rio de Janeiro, RJ, Brasil. |
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2020 |
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2020-08-31T23:58:05Z |
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2020-08-31T23:58:05Z |
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2020 |
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Azevedo, Suwellen S. D. et al. Increased expression of CDKN1A/p21 in HIV-1 controllers is correlated with upregulation of ZC3H12A/MCPIP1. Retrovirology, v. 17, n. 1, p. 1-14, 2020. |
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https://www.arca.fiocruz.br/handle/icict/43100 |
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1742-4690 |
| dc.identifier.doi.none.fl_str_mv |
10.1186/s12977-020-00522-4 |
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Azevedo, Suwellen S. D. et al. Increased expression of CDKN1A/p21 in HIV-1 controllers is correlated with upregulation of ZC3H12A/MCPIP1. Retrovirology, v. 17, n. 1, p. 1-14, 2020. 1742-4690 10.1186/s12977-020-00522-4 |
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