HIV-1 pathogenicity and virion production are dependent on the metabolic phenotype of activated CD4+ T cells.
HIV-1 pathogenicity and virion production are dependent on the metabolic phenotype of activated CD4+ T cells.
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DOI：
10.1186/s12977-014-0098-4
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发表时间：
2014-11-25
期刊：
影响因子：
3.3
通讯作者：
Huthoff H
中科院分区：
文献类型：
--
作者：
Hegedus A;Kavanagh Williamson M;Huthoff H
与所有病毒一样，HIV-1完全依赖于宿主细胞提供完成病毒复制周期和产生病毒体的代谢资源。已经确定，HIV-1在活化的CD 4 + T细胞中有效复制，而静息的CD 4 + T细胞对HIV-1感染是难治的。T细胞活化的标志是糖酵解的上调以满足细胞增殖的生物合成和生物能量需求以及通过分泌细胞因子执行效应子功能。迄今为止，HIV-1是否需要活化T细胞的高糖酵解活性来支持其复制仍然是未知的。我们报告说，在原代CD 4 + T细胞，通过糖酵解途径的流量增加后，感染HIV-1。这种糖酵解活性的增加在感染HIV-1的T细胞系中不发生。通过向细胞提供半乳糖而不是葡萄糖，前者是糖酵解的不良底物，我们监测了阻止CD 4 + T细胞中糖酵解对病毒复制周期和细胞命运的影响。我们观察到，在半乳糖中培养的HIV-1感染的原代CD 4 + T细胞比在葡萄糖中培养的细胞具有存活优势，这与半乳糖培养物中半胱天冬酶3活化和凋亡减少相一致。T细胞系不能概括这种细胞死亡的差异。最后，我们证明了病毒体的产生依赖于糖酵解，因为与含有葡萄糖的培养物相比，含有半乳糖的培养物产生的HIV-1病毒体的量减少。HIV-1在原代CD 4 + T细胞中的复制导致细胞糖酵解通量的增加。糖酵解对于病毒体产生是特别需要的，并且另外增加了感染细胞对病毒诱导的细胞死亡的敏感性。本文的在线版本（doi：10.1186/s12977-014-0098-4）包含补充材料，可供授权用户使用。
HIV-1, like all viruses, is entirely dependent on the host cell for providing the metabolic resources for completion of the viral replication cycle and the production of virions. It is well established that HIV-1 replicates efficiently in activated CD4+ T cells, whereas resting CD4+ T cells are refractory to infection with HIV-1. A hallmark of T cell activation is the upregulation of glycolysis to meet the biosynthetic and bioenergetic needs of cell proliferation and the execution of effector functions by the secretion of cytokines. To date, it has remained unknown if HIV-1 requires the high glycolytic activity of activated T cells to support its replication. We report that in primary CD4+ T cells, the flux through the glycolytic pathway is increased upon infection with HIV-1. This increase in glycolytic activity does not occur in T cell lines when infected with HIV-1. By providing cells with galactose instead of glucose, the former being a poor substrate for glycolysis, we monitored the effect of preventing glycolysis in CD4+ T cells on virus replication cycle and cell fate. We observed that HIV-1 infected primary CD4+ T cells cultured in galactose have a survival advantage over those cultured in glucose and this coincides with reduced caspase 3 activation and apoptosis in cultures with galactose. T cell lines do not recapitulate this difference in cell death. Finally, we demonstrate that virion production is dependent on glycolysis as cultures containing galactose yield reduced amounts of HIV-1 virions compared with cultures containing glucose. The replication of HIV-1 in primary CD4+ T cells causes an increase in glycolytic flux of the cell. Glycolysis is particularly required for virion production and additionally increases the sensitivity of the infected cell to virus-induced cell death. The online version of this article (doi:10.1186/s12977-014-0098-4) contains supplementary material, which is available to authorized users.
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影响因子：
64.5
作者：
Chang CH;Curtis JD;Maggi LB Jr;Faubert B;Villarino AV;O'Sullivan D;Huang SC;van der Windt GJ;Blagih J;Qiu J;Weber JD;Pearce EJ;Jones RG;Pearce EL
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影响因子：
5.5
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影响因子：
3.3
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Gelderblom, Huub C.;Vatakis, Dimitrios N.;Burke, Sean A.;Lawrie, Steven D.;Bristol, Gregory C.;Levy, David N.
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