High prevalence of cigarette smoking in HIV patients is associated with increased HIV pathogenesis and
disease progression. While the effect of smoking on the occurrence of
lung cancer has been studied extensively, the association between smoking and HIV pathogenesis is poorly studied. We have recently shown the possible role of
cytochrome P450 (CYP) in smoking/
nicotine-mediated viral replication. In this review, we focus on the potential role of CYP pathway in
polycyclic aromatic hydrocarbons (PAH), important constituents of cigarette
smoke, mediated HIV pathogenesis. More specifically, we will discuss the role of
CYP1A1 and CYP1B1, which are the major PAH-activating CYP
enzymes. Our results have shown that treatment with cigarette
smoke condensate (CSC) increases viral replication in HIV-infected macrophages. CSC contains PAH, which are known to be activated by
CYP1A1 and CYP1B1 into procarcinogens/toxic metabolites. The expression of these CYPs is regulated by
aryl hydrocarbon receptors (AHR), the cellular target of PAH, and an important player in various diseases including
cancer. We propose that PAH/AHR-mediated CYP pathway is a novel target to develop new interventions for HIV positive smokers.