Estudio del papel de Galectina1 en la modulación de la replicación y dinámica de reservorios de VIH-1
Antiretroviral therapy (ART) efficiently decreases circulating HIV levels but does not eradicate the virus, which persists in a small pool of long-lived latently infected cells. The maintenance of this viral reservoir is associated with persistent inflammation during ART. Galectin-1 (Gal1) is an end...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
| Publicado: |
Facultad de Farmacia y Bioquímica
2020
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_6298 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_6298.dir/6298.PDF |
| Aporte de: |
| Sumario: | Antiretroviral therapy (ART) efficiently decreases circulating HIV levels but does not
eradicate the virus, which persists in a small pool of long-lived latently infected cells. The
maintenance of this viral reservoir is associated with persistent inflammation during ART.
Galectin-1 (Gal1) is an endogenous lectin with important immunomodulatory functions. We
show that Gal1 reverses HIV-1 latency in J-LAT cells in a glycan-dependent manner and
through the activation of the NF-?B signaling pathway. Moreover, Gal1 promotes viral production
in productively HIV-1-infected primary CD4+ T cells. Analysis of plasma samples from HIV-1
infected individuals revealed an increase in Gal1 levels, as compared to uninfected donors,
independently of both viral load and CD4+ T cell numbers. Remarkably, we observed a positive
correlation between circulating Gal1 levels and HIV reservoir size suggesting that Gal1 could be
modulating the transcriptional activity of latently infected cells in vivo. Finally, we show that
extracellular vesicles isolated from the blood of HIV-1 infected individuals induce the secretion
of Gal1 by macrophages. In conclusion, we propose that the increased levels of Gal1 promote
HIV-1 transcription. Thus, by modulating reservoir dynamics, Gal1 and EVs link inflammation
with HIV-1 persistence in ART-treated individuals. |
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