scholarly journals Interrogating the impact of combination antiretroviral therapies on HIV‐associated neurocognitive disorders

HIV Medicine ◽  
2021 ◽  
Author(s):  
Ishta Sharma
Keyword(s):  
Neurocognitive Disorders ◽  
Antiretroviral Therapies ◽  
The Impact ◽  
Hiv Associated Neurocognitive Disorders

scholarly journals HIV-1 Vpr-Induced Proinflammatory Response and Apoptosis Are Mediated through the Sur1-Trpm4 Channel in Astrocytes

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
Author(s):  
Ge Li ◽  
Tapas Makar ◽  
Volodymyr Gerzanich ◽  
Sudhakar Kalakonda ◽  
Svetlana Ivanova ◽  
...  
Keyword(s):  
Neurocognitive Disorders ◽  
Proinflammatory Response ◽  
Normal Life ◽  
Chronic Neuroinflammation ◽  
Antiretroviral Therapies ◽  
Tnf Α ◽  
Trpm4 Channel ◽  
Hiv 1 ◽  
Hiv Associated Neurocognitive Disorders ◽  
Brain Tissues

ABSTRACT 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. IMPORTANCE Effective antiretroviral therapies can now prolong patients’ lives to nearly normal life span. The current challenge faced by many HIV-infected patients is chronic neuroinflammation and neurotoxicity that contributes to HIV-associated neurocognitive disorders (HAND). We show here that the expression of HIV-1 infection and Vpr correlates with the activation of proinflammatory markers (Toll-like receptor 4 [TLR4], tumor necrosis factor alpha [TNF-α], and NF-κB) and the sulfonylurea receptor 1 (Sur1)-transient receptor potential melastatin 4 (Trpm4) channel in astrocytes of brain tissues. We further show that an FDA-approved Sur1 inhibitory drug called glibenclamide significantly ameliorates apoptotic astrocytic cell death caused by HIV-1 Vpr, which could potentially open the possibility of repurposing glibenclamide for treating HAND.

Youth perinatal HIV-associated neurocognitive disorders: association with functional impairment

AIDS Care ◽  
2021 ◽  
pp. 1-5
Author(s):  
Nicole Phillips ◽  
Kevin G. F. Thomas ◽  
Bulelwa Mtukushe ◽  
Landon Myer ◽  
Heather J. Zar ◽  
...  
Keyword(s):  
Functional Impairment ◽  
Neurocognitive Disorders ◽  
Perinatal Hiv ◽  
Hiv Associated Neurocognitive Disorders
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