Cerebral endothelial cell response to HIV challenge is affected by exposure to protease inhibitors

• Published in: Journal of neurovirology Vol. 12; p. 12
• Main Authors: Chao, Y S, Grigorian, A, Hurford, R, Patel, N, Langford, D T
• Format: Journal Article
• Language: English
• Published: 01-05-2006
• Subjects: Human immunodeficiency virus
• ISSN: 1355-0284

To maintain viral suppression, HIV patients adherent to anti-retroviral (ART) medications experience fairly consistent plasma levels of the drug(s). In this scenario, the cerebral endothelial cells (CEC) of the blood-brain interface (BBI) are bathed regularly in ART drugs. Our hypothesis, based on the fact that many components of the highly active ART regimen are not benign, is that chronic exposure of CEC to ART drugs will alter signaling among components of the BBI, and ultimately contribute to changes in cellular responses to viral challenge at rebound. While reported deleterious effects of ART on host cells are diverse and drug and cell type specific, commonalities such as mitochondrial toxicity and dysfunction are observed. Numerous studies describe mechanistically the effects of ART on host cell fitness and signaling, however, relatively few studies consider the impact of chronic exposure to components of ART on the host's response to viral challenge. Studies show that while fibroblast growth factor 2 (FGF2) can protect CEC from the toxic effects of HIV gp120 (1), chronic exposure of CEC to some HIV protease inhibitors abolishes the ability of FGF2 to protect from gp120. Likewise, autopsy studies in HIV encephalitic patients indicate that individuals with low levels of astrocyte-derived FGF2 expression have markedly increased CEC apoptosis (2). To address the potential effects that exposure to ART may have on CEC signaling and fitness, we investigated changes in gene expression patterns in CEC treated with PIs and exposed to HIV. Our results indicate that exposure to HIV PIs induces changes in the expression of gene families important in maintaining CEC fitness and that the cell's signaling response to HIV exposure is affected by exposure to PIs.