The Alpha 7-Nicotinic Receptor Is Upregulated In Immune Cells From Hiv-Seropositive Women: Consequences To The Cholinergic Anti-Inflammatory Response

Antiretroviral therapy partially restores the immune system and markedly increases life expectancy of HIV-infected patients. However, antiretroviral therapy does not restore full health. These patients suffer from poorly understood chronic inflammation that causes a number of AIDS and non-AIDS complications. Here we show that chronic inflammation in HIV+ patients may be due to the disruption of the cholinergic anti-inflammatory pathway by HIV envelope protein gp120(IIIB). Our results demonstrate that HIV gp120(IIIB) induces alpha 7 nicotinic acetylcholine receptor (alpha 7) upregulation and a paradoxical proinflammatory phenotype in macrophages, as activation of the upregulated a7 is no longer capable of inhibiting the release of proinflammatory cytokines. Our results demonstrate that disruption of the cholinergic-mediated anti-inflammatory response can result from an HIV protein. Collectively, these findings suggest that HIV tampering with a natural strategy to control inflammation could contribute to a crucial, unresolved problem of HIV infection: chronic inflammation.