Author | Temerozo, Jairo R. | |
Author | Azevedo, Suwellen S. D. de | |
Author | Insuela, Daniella B. R. | |
Author | Vieira, Rhaíssa C. | |
Author | Ferreira, Pedro L. C. | |
Author | Carvalho, Vinícius F. | |
Author | Bello, Gonzalo | |
Author | Bou-Habib, Dumith Chequer | |
Access date | 2018-10-04T13:41:00Z | |
Available date | 2018-10-04T13:41:00Z | |
Document date | 2018 | |
Citation | TEMEROZO, Jairo R. et al. The neuropeptides vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide control HIV-1 infection in macrophages through activation of protein kinases A and C. Frontiers in Immunology, v. 9, n. 1336, p. 1-16, June 2018. | |
ISSN | 1664-3224 | |
URI | https://www.arca.fiocruz.br/handle/icict/29332 | |
Description | Produção científica do Laboratório de Aids e Imunologia Molecular. | pt_BR |
Description | Produção científica do Laboratório de Pesquisa sobre o Timo. | pt_BR |
Language | eng | en_US |
Publisher | Frontiers Media | |
Rights | open access | |
Subject in Portuguese | HIV-1 | pt_BR |
Subject in Portuguese | Neuropeptídeos | pt_BR |
Subject in Portuguese | Proteína Quinase C | pt_BR |
Subject in Portuguese | Proteína Quinase A | pt_BR |
Subject in Portuguese | Macrófagos | pt_BR |
Subject in Portuguese | Peptídeo Intestinal Vasoativo | pt_BR |
Subject in Portuguese | Polipeptídeo Hipofisário Ativador de Adenilato Ciclase | pt_BR |
Title | The neuropeptides vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide control HIV-1 infection in macrophages through activation of protein kinases A and C | en_US |
Type | Article | |
DOI | 10.3389/fimmu.2018.01336 | |
Abstract | Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are highly similar neuropeptides present in several tissues, endowed with immunoregulatory functions and other systemic effects. We previously reported that both neuropeptides reduce viral production in HIV-1-infected primary macrophages, with the participation of β-chemokines and IL-10, and now we describe molecular mechanisms engaged in this activity. Macrophages exposed to VIP or PACAP before HIV-1 infection showed resistance to viral replication, comparable to that observed when the cells were treated after infection. Also, multiple treatments with a suboptimal dose of VIP or PACAP after macrophage infection resulted in a decline of virus production similar to the inhibition promoted by a single exposure to the optimal inhibitory concentration. Cellular signaling pathways involving cAMP production and activation of protein kinases A and C were critical components of the VIP and PACAP anti-HIV-1 effects. Analysis of the transcription factors and the transcriptional/cell cycle regulators showed that VIP and PACAP induced cAMP response element-binding protein activation, inhibited NF-kB, and reduced Cyclin D1 levels in HIV-1-infected cells. Remarkably, VIP and PACAP promoted G-to-A mutations in the HIV-1 provirus, matching those derived from the activity of the APOBEC family of viral restriction factors, and reduced viral infectivity. In conclusion, our findings strengthen the antiretroviral potential of VIP and PACAP and point to new therapeutic approaches to control the progression of HIV-1 infection. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil. | |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil. | |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil. | |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil. | |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil. | |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil. | |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil. | |
Subject | HIV-1 | en_US |
Subject | Vasoactive intestinal peptide | en_US |
Subject | Pituitary adenylate cyclase-activating polypeptide | en_US |
Subject | Neuropeptides | en_US |
Subject | Macrophages | en_US |
Subject | Protein kinase C | en_US |
Subject | Protein kinase A | en_US |
DeCS | Polipeptídeo Hipofisário Ativador de Adenilato Ciclase | pt_BR |
DeCS | Peptídeo Intestinal Vasoativo | pt_BR |
e-ISSN | 1664-3224 | |