Evidence for Altered Glutamine Metabolism in Human Immunodeficiency Virus Type 1 Infected Primary Human CD4+ T Cells

Andrea Hegedus, Maia Kavanagh Williamson, Mariam B. Khan, Julianna Dias Zeidler, Andrea T. Da Poian, Tatiana El-Bacha, Eduard A. Struys, Hendrik Huthoff*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1236-1247
Number of pages12
JournalAIDS Research and Human Retroviruses
Volume33
Issue number12
DOIs
Publication statusPublished - 1 Dec 2017

Cite this