HIV-1 pathogenicity and virion production are dependent on the metabolic phenotype of activated CD4+ T cells

Retrovirology

Hendrik Huthoff¹  Maia Kavanagh Williamson¹  Andrea Hegedus¹ 

[1] Department of Infectious Diseases, King¿s College London, 2nd Floor Borough Wing, Guy¿s Hospital, Great Maze Pond, London SE1 9RT, UK

关键词: T lymphocytes;    Glucose;    Apoptosis;    Virion assembly;    Glycolysis;    Metabolism;    Human immunodeficiency virus;   

Others  :  1151991
DOI  :  10.1186/s12977-014-0098-4

 received in 2014-08-05, accepted in 2014-10-24,  发布年份 2014

【 摘 要 】

Background

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2014 Hegedus et al.; licensee BioMed Central Ltd.

【 图 表 】

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