Evidence for Altered Glutamine Metabolism in Human Immunodeficiency Virus Type 1 Infected Primary Human CD4(+) T Cells.
Evidence for Altered Glutamine Metabolism in Human Immunodeficiency Virus Type 1 Infected Primary Human CD4(+) T Cells.
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DOI：
10.1089/aid.2017.0165
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发表时间：
2017-12
影响因子：
1.5
通讯作者：
Huthoff H
中科院分区：
文献类型：
--
作者：
Hegedus A;Kavanagh Williamson M;Khan MB;Dias Zeidler J;Da Poian AT;El-Bacha T;Struys EA;Huthoff H
谷氨酰胺是一种条件必需氨基酸，其通过充当蛋白质氨基酸、生物合成反应的氮供体以及柠檬酸或三羧酸循环的底物而成为增殖组织的重要代谢资源。人类免疫缺陷病毒1型（HIV-1）有效感染活化的CD 4 + T细胞，已知活化的CD 4 + T细胞需要谷氨酰胺进行增殖和执行效应子功能。作为一种病毒，HIV-1完全依赖于宿主的新陈代谢来支持其复制。在这项研究中，我们比较了HIV-1感染与未感染的活化原代人CD 4 + T细胞的谷氨酰胺代谢。我们报告说，谷氨酰胺浓度升高，在HIV-1感染的细胞，谷氨酰胺是重要的，以支持HIV-1的复制，虽然后者是密切相关的谷氨酰胺依赖的细胞存活。代谢示踪实验表明，谷氨酰胺衍生的碳进入柠檬酸循环不受HIV-1感染的影响，但HIV-1感染的细胞中谷氨酰胺衍生的谷氨酸的分泌增加。代谢谷氨酰胺的关键酶的蛋白质印迹法显示，谷氨酰胺酶亚型、KGA和CAG以及靶向谷氨酰胺衍生的氮朝向核苷酸合成的PPAT酶的表达存在显著差异。总之，这表明HIV-1感染CD 4 + T细胞导致细胞谷氨酰胺代谢的显著变化。
Glutamine is a conditionally essential amino acid that is an important metabolic resource for proliferating tissues by acting as a proteinogenic amino acid, a nitrogen donor for biosynthetic reactions and as a substrate for the citric acid or tricarboxylic acid cycle. The human immunodeficiency virus type 1 (HIV-1) productively infects activated CD4+ T cells that are known to require glutamine for proliferation and for carrying out effector functions. As a virus, HIV-1 is furthermore entirely dependent on host metabolism to support its replication. In this study, we compared HIV-1 infected with uninfected activated primary human CD4+ T cells with regard to glutamine metabolism. We report that glutamine concentrations are elevated in HIV-1-infected cells and that glutamine is important to support HIV-1 replication, although the latter is closely linked to the glutamine dependency of cell survival. Metabolic tracer experiments showed that entry of glutamine-derived carbon into the citric acid cycle is unaffected by HIV-1 infection, but that there is an increase in the secretion of glutamine-derived glutamic acid from HIV-1-infected cells. Western blotting of key enzymes that metabolize glutamine revealed marked differences in the expression of glutaminase isoforms, KGA and CAG, as well as the PPAT enzyme that targets glutamine-derived nitrogen toward nucleotide synthesis. Altogether, this demonstrates that infection of CD4+ T cells with HIV-1 leads to considerable changes in the cellular glutamine metabolism.