HIV-1 Vpr-Induced Proinflammatory Response and Apoptosis Are Mediated through the Sur1-Trpm4 Channel in Astrocytes.
Animals
Apoptosis
Astrocytes
/ metabolism
Biomarkers
Brain
/ metabolism
Cell Line, Tumor
Cytokines
/ metabolism
Fluorescent Antibody Technique
HIV Infections
/ metabolism
HIV-1
/ physiology
Host-Pathogen Interactions
/ genetics
Humans
Immunity, Innate
Immunohistochemistry
Inflammation Mediators
/ metabolism
Mice
Protein Binding
Sulfonylurea Receptors
/ metabolism
TRPM Cation Channels
/ metabolism
vpr Gene Products, Human Immunodeficiency Virus
/ metabolism
HIV-associated neurocognitive disorders (HAND)
Human immunodeficiency virus type 1 (HIV-1)
NF-κB
Sur1-Trpm4 channel
TLR4
TNF-α
astrocytes
brain tissues
glibenclamide
host-pathogen interactions
human immunodeficiency virus
neuroinflammation
neurotoxicity
viral protein R (Vpr)
Journal
mBio
ISSN: 2150-7511
Titre abrégé: mBio
Pays: United States
ID NLM: 101519231
Informations de publication
Date de publication:
08 12 2020
08 12 2020
Historique:
entrez:
9
12
2020
pubmed:
10
12
2020
medline:
8
9
2021
Statut:
epublish
Résumé
Successful treatment of HIV-infected patients with combinational antiretroviral therapies (cART) can now prolong patients' lives to nearly normal life spans. However, the new challenge faced by many of those HIV-infected patients is chronic neuroinflammation and neurotoxicity that often leads to HIV-associated neurocognitive disorders (HAND). However, the mechanism of neuropathogenesis underlying HAND, especially in those who are under cART, is not well understood. HAND is typically characterized by HIV-mediated glial neuroinflammation and neurotoxicity. However, the severity of HAND does not always correlate with HIV-1 viral load but, rather, with the extent of glial activation, suggesting that other HIV-associated factors might contribute to HAND. HIV-1 viral protein R (Vpr) could be one of those viral factors because of its association with neuroinflammation and neurotoxicity. The objective of this study was to delineate the specific roles of HIV-1 infection and Vpr in the activation of neuroinflammation and neurotoxicity, and the possible relationships with the Sur1-Trpm4 channel that contributes to neuroinflammation and neuronal death. Here, we show that HIV-1 expression correlates with activation of proinflammatory markers (TLR4, TNF-α, and NF-κB) and the Sur1-Trpm4 channel in astrocytes of HIV-infected postmortem human and transgenic Tg26 mouse brain tissues. We further show that Vpr alone activates the same set of proinflammatory markers and Sur1 in a glioblastoma SNB19 cell line that is accompanied by apoptosis. The Sur1 inhibitor glibenclamide significantly reduced Vpr-induced apoptosis. Together, our data suggest that HIV-1 Vpr-induced proinflammatory response and apoptosis are mediated at least in part through the Sur1-Trpm4 channel in astrocytes.
Identifiants
pubmed: 33293383
pii: mBio.02939-20
doi: 10.1128/mBio.02939-20
pmc: PMC8534293
pii:
doi:
Substances chimiques
Biomarkers
0
Cytokines
0
Inflammation Mediators
0
Sulfonylurea Receptors
0
TRPM Cation Channels
0
TRPM4 protein, mouse
0
vpr Gene Products, Human Immunodeficiency Virus
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NINDS NIH HHS
ID : R01 NS061934
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS105633
Pays : United States
Organisme : BLRD VA
ID : I01 BX004652
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL082517
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS107262
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS060801
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS102589
Pays : United States
Informations de copyright
Copyright © 2020 Li et al.
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