Author | Temerozo, Jairo R. | |
Author | Joaquim, Rafael | |
Author | Regis, Eduardo G. | |
Author | Savino, Wilson | |
Author | Bou-Habib, Dumith Chequer | |
Access date | 2015-09-28T13:02:39Z | |
Available date | 2015-09-28T13:02:39Z | |
Document date | 2013 | |
Citation | TEMEROZO, Jairo R.; et al. Macrophage Resistance to HIV-1 Infection Is Enhanced by the Neuropeptides VIP and PACAP. Plos One, v.8, n.6, e67701, 8p, June 2013. | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/11835 | |
Language | eng | pt_BR |
Publisher | Plos One | pt_BR |
Rights | open access | |
Title | Macrophage Resistance to HIV-1 Infection Is Enhanced by the Neuropeptides VIP and PACAP | pt_BR |
Type | Article | |
DOI | 10.1371/journal.pone.0067701 | pt_BR |
Abstract | It is well established that host factors can modulate HIV-1 replication in macrophages, critical cells in the pathogenesis of
HIV-1 infection due to their ability to continuously produce virus. The neuropeptides VIP and PACAP induce wellcharacterized
effects on macrophages through binding to the G protein-coupled receptors VPAC1, VPAC2 and PAC1, but
their influence on HIV-1 production by these cells has not been established. Here, we describe that VIP and PACAP reduce
macrophage production of HIV-1, acting in a synergistic or additive manner to decrease viral growth. Using receptor
antagonists, we detected that the HIV-1 inhibition promoted by VIP is dependent on its ligation to VPAC1/2, whereas
PACAP decreases HIV-1 growth via activation of the VPAC1/2 and PAC1 receptors. Specific agonists of VPAC2 or PAC1
decrease macrophage production of HIV-1, whereas sole activation of VPAC1 enhances viral growth. However, the
combination of specific agonists mimicking the receptor preference of the natural neuropeptides reproduces the ability of
VIP and PACAP to increase macrophage resistance to HIV-1 replication. VIP and PACAP up-regulated macrophage secretion
of the b-chemokines CCL3 and CCL5 and the cytokine IL-10, whose neutralization reversed the neuropeptide-induced
inhibition of HIV-1 replication. Our results suggest that VIP and PACAP and the receptors VPAC2 and PAC1 could be used as
targets for developing alternative therapeutic strategies for HIV-1 infection. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Central Hospital of Maputo. Laboratory of Microbiology. Maputo, Mozambique. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | HIV-1 Infection | pt_BR |
Subject | Macrophage | pt_BR |
Subject | PACAP | pt_BR |
Subject | VIP | pt_BR |
Subject | Neuropeptides | pt_BR |
DeCS | Neuropeptídeos | pt_BR |
DeCS | Macrófagos | pt_BR |
DeCS | Infecções por HIV | pt_BR |
DeCS | Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase | pt_BR |
DeCS | Receptores de Peptídeo Intestinal Vasoativo | pt_BR |