HIV infection of T cells enhances production of proteins associated with cardiovascular and other metabolic disorders
Objective: The goal of this study is to delineate molecular mechanisms by which most chronically HIV infected individuals develop lipodystrophy and cardiovascular, neurological and other metabolic disorders despite the reduction of virus-load by antiviral drugs. Since HIV modulates cellular proteins to facilitate its own survival and replication, we studied genome-wide changes in protein profiles before and after HIV infection of human cells.
Methods: Proteomics technologies including 2-D-gel electrophoresis and mass spectrometry were used to study changes in cellular protein expression patterns after HIV infection of a human T cell line in vitro. By the use of various bioinformatics and statistical programs both the upregulated and downregulated proteins and protein-protein interaction pathways were analyzed in relation to their putative biological effects in various human diseases.
Results: Analyses of >250 differentially regulated proteins in HIV-infected T cells and those present in the counterpart uninfected cells revealed a set of about 40 proteins that included NOS2A, VLDLR, APOA-I, APOB-100, LRP1 and others that were upregulated after HIV infection or not detected in uninfected T cells. In non-HIV infected individuals, these proteins have been considered as risk factors for the development of lipid abnormalities, atherosclerosis and other metabolic disorders. In addition, several proteins that were downregulated post-HIV infection were found to increase the expression of genes involved in the fatty acid synthesis, enhanced calcium ion transport, augmentation of plaque formation, clogging of arteries and damage of blood vessels.
Conclusions: Our studies demonstrate that HIV infection alters the entire cellular milieu by inducing new proteins and upregulating or downregulating numerous existing proteins. We have identified proteins that may disrupt normal metabolic pathways and alter protein-protein interaction networks leading to enhanced fatty acid synthesis, lipodystrophy, oxidative stress, vessel damage, plaque formation and lipid abnormalities that can potentially lead to atherosclerosis and other cardiovascular-related disorders in chronically HIV-infected individuals.
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention
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HIV infection of T cells enhances production of proteins associated with cardiovascular and other metabolic disorders.
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention: