How Does HIV Lower HDL Cholesterol Levels?
The pathogenesis of low HDL cholesterol levels in untreated HIV infection is unknown. In a study recently published in PLoS Biology, Mujawar et al. investigated whether these lower levels might be due to impaired cholesterol efflux from macrophages [10], a process mediated by the ABCA1 cell-surface cholesterol transporter. ABCA1 lipidates apoA-I, the major apolipoprotein in HDL, and thus plays a central role in formation of nascent HDL. Mutations in ABCA1 cause Tangier disease, which is associated with low HDL cholesterol and accelerated atherosclerosis [11]. The researchers found that expression of HIV nef, a protein that enhances HIV replication and infectivity, specifically inhibited ABCA1-dependent cholesterol efflux from macrophages (the precursors of foam cells in atherosclerotic plaque) and re-localized ABCA1 to an exclusive plasma membrane distribution. While nef-transfected cells exhibited increased apoA-I binding, apoA-I internalization was blocked, suggesting that nef at the
