# Role of pannexin-1 hemichannels in NeuroAIDS

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2021 · $524,841

## Abstract

Project Abstract:
According to WHO and UN reports, in 2014 an estimated 34 million persons worldwide were living with
HIV. In addition to compromising the immune system, HIV can also infect the CNS early during the
disease, leading to devastating neurological consequences (NeuroAIDS). A growing body of evidence
indicates that neurological damage in NeuroAIDS is triggered not by the active viral replication but by the
transmigration of HIV-infected leukocytes into the brain and the associated neuroinflammation. While it is
well established that HIV uses host-encoded proteins to facilitate viral infection, replication and
transmigration into the CNS, specific host factors involved in the pathogenesis of NeuroAIDS are still
extremely poorly understood. Our laboratory recently identified pannexin-1 channels as essential
components of the HIV life cycle in immune cells as well as in the pathogenesis of NeuroAIDS. In
particular, we and others have demonstrated that pannexin-1 channel opening facilitates multiple steps of
HIV-mediated CNS compromise, including: (1) regulation of CCR5 surface aggregation and trafficking in
response to HIV infection; (2) HIV entry by direct regulation of the channel opening and subsequent
release of intracellular ATP, auto-activating purinergic receptors; (3) release of intracellular factors such
as ATP that promote inflammation; (4) monocyte differentiation and maturation in response to chemokines
and/or HIV; (5) increased expression of several adhesion molecules required for leukocytes to
transmigrate across the BBB; (6) neuroinflammation. We also found that ATP compromises BBB integrity
and function, and our analysis of a large number of patient samples suggests that circulating ATP may be
a biomarker of CNS disease. Our preliminary data indicate that different ethnic groups carry specific
pannexin-1 polymorphisms and have differential expression and opening of this channel, potentially
underlying, at least in part, the observed variation in susceptibility to HIV infection and NeuroAIDS among
different ethnicities. Our recent preliminary data indicate that circulating ATP concentrations and their
correlation with CNS compromise are also ethnicity related. Importantly, pannexin-1 channels have
excellent potential as a therapeutic target because (1) their opening can be effectively blocked in vivo
using several pannexin-1 channel blockers, including a specific mimetic peptide we recently designed;
and (2) these channels mostly exist in a closed state under physiological conditions, minimizing potential
side effects. This proposal is designed to define the mechanisms linking pannexin-1 channel opening to
HIV receptor expression, trafficking, and function (Aim 1), leukocyte differentiation and transmigration into
the CNS (Aim 2), and the role of neuroinflammatory factors released through the channel in BBB and
CNS function (Aim 3). Finally, in Aim 4 we will examine the role of pannexin-1 channels in two animal
models. Toge...

## Key facts

- **NIH application ID:** 10166965
- **Project number:** 5R01NS105584-06
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Eliseo A Eugenin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $524,841
- **Award type:** 5
- **Project period:** 2018-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10166965

## Citation

> US National Institutes of Health, RePORTER application 10166965, Role of pannexin-1 hemichannels in NeuroAIDS (5R01NS105584-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10166965. Licensed CC0.

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