hiv-1 virion accumulation and atp-induced release in human primary monocyte-derived macrophages aids...
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HIV-1 virion accumulation and ATP-induced release in human
primary monocyte-derived macrophages
AIDS Immunopathogenesis UnitVita-Salute San Raffaele University, Milan, Italy
Francesca GrazianoPhD Student
Poster n°WEPDA0103
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Macrophage
Virion synthesis & accumulation
CD4+ T cell
Cell Death
What is the nature of HIV-containing vacuoles?
What else is contained in addition to HIV virions?
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ATPP2X7
Receptor
Permeabilized
plasma membrane
Pyroptotic/NecroticPathway
Exosome Pathway
Microvesicles Pathway
Autophagic Pathway
HIV-1
Hypothesis:Are the intracellular HIV-1 virions released by extracellular ATP stimulation, like IL-1b?
IL-1 β ?
The IL-1b Release Pathway. A potential model for HIV-1 infection of Mø?
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MODEL (I): Chronically infected promonocytic cell line U1 (2 copies of integrated virus/cell).
N=8
* *** ***oxATP
ATP
HIV-1
1 min. 5 min. 10 min.
Untreated
oxATP
ATP
N=3
**
IL-1b
N=8
uPA prevents virion release from PMA stimulated U1 cells
uPA: urokinase-type Plasminogen Activator
ATP induces a release pathway in stimulated U1 cells
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Alternatively Activated M2-MDM
Classically Activated M1-MDM
IL-4IFN-MDM
N=18
MODEL (II)HIV-1 Infection of primary monocyte-derived macrophages (MDM)
N=25MDM
10’ 20’ 30’
M1-MDM M2-MDM
10’ 20’ 30’ 10’ 20’ 30’
Untreated
ATP
ATP induces the release of HIV virions from HIV-1 infected MDM
p24
UN 1 mM ATP
FSC
MDMUN 1 mM ATP
M2-MDM
ATP reduces the intracellular amount
of HIV-1 virions16,7 9,63 20,2 6,78
1 representative of 7
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Conclusions
HIV-1 virions accumulate in intracellular vacuoles in differentiated U1 cells and primary MDM.
ATP promotes the release of IL-1b and HIV-1 virions in both cell types.
These results suggest that HIV-1 exploits the microvesicle pathway to be released from infected macrophages.
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Acknowledgements
AIDS Immunopathogenesis Unit
Guido Poli
Massimo Alfano
Elisa Vicenzi
INSPE Division of Neuroscience
Roberto Furlan
Livia Garzetti
Humanitas Clinical and Research Center
Massimo Locati
Poster N° WEPDA0103