Review Article

The Roles of Genetic Polymorphisms and Human Immunodeficiency Virus Infection in Lipid Metabolism

Figure 1

At tissues, human immunodeficiency virus type 1 (HIV-1) infects macrophages using the CD4 as receptor and the CCR5 as coreceptor and induces the local immune response. At peripheral circulation, HIV-1 infects Th1 CD4+ cells, particularly by the coreceptor CXCR4 that persists latently infected or becomes a productively infected cell. The viral proteins induce an proinflammatory response in peripheral circulation and in the tissues and decrease plasma high-density lipoprotein cholesterol (HDL-C) by impairing the cholesterol-dependent efflux transporter ATP-binding cassette protein A1 (ABCA1) in human macrophages, a condition that is highly atherogenic. Additionally, the viral proteins and the proinflammatory cytokines interleukin 1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor α (TN-Fα), and interferon α (IFN-α) stimulate endothelial lipase and certain acute phase proteins, such as serum amyloid A. The viral proteins also exert effects on the adipocytes resulting mitochondrial dysfunction, reactive oxygen species (ROS) production, and insulin resistance and decrease adiponectin. The chronic inflammatory processes increase the production of these proinflammatory cytokines, resulting in the impaired clearance of triglyceride-rich lipoproteins (TG-RLP) and insulin resistance. All these mechanisms increase the risk of cardiovascular diseases in the HIV-1-infected individuals.
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