HIV-1 activation of P2X7 is shown to stimulate cation flux which is both required for HIV-1 entry and can activate inflammation by pro-inflammatory cytokine production and T-cell death.

HIV-1 causes an incurable disease and while antiretroviral therapy is effective at suppressing viremia, long term sequelae of inflammation account for premature aging, higher rates of cardiovascular disease, and neoplasms. Our laboratory seeks to identify a novel mechanism of HIV-associated inflammation through purinergic signaling. This pathway detects extracellular nucleotide and is critical to global inflammation and has recently been demonstrated to be required for HIV-1 infection. We have observed that purinergic inhibition potently blocks HIV-1 productive infection in both cell free and cell-associated models. We are further seeking to characterize specific mechanism by which this inhibition takes place. This project has broad implications for direct anti-retroviral therapeutic options as well as adjunctive anti-inflammatory therapeutics and prognostic measurements. Because purinergic signaling may directly impact HIV-1 infection and also may have effects on inflammation, targeting this pathway may have a dual benefit in the treatment of HIV-infected patients.

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