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The Metabolism of the HIV-1 Infected CD4+ T Cell

Maia Kavanagh Williamson

出版	King's College London, 2018
URL	http://books.google.com.hk/books?id=JmaL0AEACAAJ&hl=&source=gbs_api

註釋

As obligate intracellular pathogens that have no metabolism of their own, viruses rely on their host cell for the provision of bioenergetic and biosynthetic precursors to support their replication. Metabolic perturbations have now been documented for a number of viruses including Human Cytomegalovirus, Hepatitis C and Dengue Virus. We here report that HIV-1 infection of primary CD4+ T cells is manifested by a marked increase in glucose uptake and its downstream metabolism. The prevention of glycolysis significantly reduces HIV-1 virion production and infectivity. Throughout these analyses, we found inconstancies between the metabolic programmes of primary CD4+ T cells and immortalised T cell lines, thereby demonstrating that these cell lines do not represent suitable models for metabolic analysis of HIV-1 infection. Building on observations of enhanced glucose uptake in HIV-1 infected cells, we performed the first comprehensive analysis of the expression of glucose transporters in human CD4+ T cells and demonstrated that GLUT1, 3, 4 and 6 are upregulated in response to antigenic stimulation and are further enhanced by active HIV-1 replication. Using small molecular inhibitors, we demonstrated redundancy in the contribution of GLUTl,3, 4 and 6 proteins to CD4+ T cell glucose uptake and identified a potential role for glucose metabolism in supporting HIV-1 Env glycoprotein biosynthesis. Increased glycolytic activity in HIV-1 infected cells correlated with increased activity of Hexokinase and overexpression of Hexokinase 1but not Hexokinase 2. The increased expression of Hexokinase 1is also dependent on active HIV-1 replication but is not mediated by the activity of any of the viral accessory proteins in isolation.