Regulatory T Cells Contribute to HIV-1 Reservoir Persistence in CD4+ T Cells Through Cyclic Adenosine Monophosphate-Dependent Mechanisms in Humanized Mice In Vivo.
J Infect Dis
; 216(12): 1579-1591, 2017 12 19.
Article
en En
| MEDLINE
| ID: mdl-29045701
ABSTRACT
Background:
Regulatory T cells (Tregs) suppress T-cell immune activation and human immunodeficiency virus type 1 (HIV-1) replication, but the role of Tregs in HIV-1 reservoir persistence is poorly defined.Methods:
Tregs were depleted by denileukin diftitox in humanized mice with chronic HIV-1 infection. Viral replication in lineage cells was determined by p24 expression. Levels of HIV-1 RNA and DNA in human cells, as well as replication-competent-virus-producing cells, were measured to quantified viral replication and reservoirs.Results:
Treg depletion resulted in a blip of HIV-1 replication in T cells but not in myeloid cells. The major activated reservoir cells were memory CD4+ T cells in vivo. Interestingly, the transient activation of viral replication led to HIV-1 reservoir reduction after viremia resuppression, as indicated by the quantity of HIV-1 DNA and replication-competent-virus-producing cells. Furthermore, we demonstrated that Tregs use cyclic adenosine monophosphate (cAMP)-dependent protein kinase A pathway to inhibit HIV-1 activation and replication in resting conventional T cells in vitro.Conclusion:
Tregs suppress HIV-1 replication in T cells and contribute to HIV-1 reservoir persistence. cAMP produced in Tregs is involved in their suppression of viral gene activation and expression. Treg depletion combined with combination antiretroviral therapy provides a novel strategy for HIV-1 cure.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Replicación Viral
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Infecciones por VIH
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VIH-1
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Linfocitos T Reguladores
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Linfocitos T Colaboradores-Inductores
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AMP Cíclico
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Infect Dis
Año:
2017
Tipo del documento:
Article