Evidence for altered glutamine metabolism in HIV-1 infected primary human CD4+ T cells

TY - JOUR

T1 - Evidence for altered glutamine metabolism in HIV-1 infected primary human CD4+ T cells

AU - Hegedus, Andrea

AU - Kavanagh Williamson, Maia

AU - Khan, Mariam Bibi

AU - Dias Zeidler, Juliana

AU - Da Poian, Andrea

AU - El Bacha, Tatiana

AU - Struys, Eduard

AU - Huthoff, Hendrik

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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 (TCA), 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 regards 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, though 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 metabolise glutamine revealed marked differences in the expression of glutaminase isoforms KGA and CAG as well as the PPAT enzyme that targets glutamine-derived nitrogen towards nucleotide synthesis. Together, this demonstrates that infection of CD4+ T cells with HIV-1 leads to considerable changes in the cellular glutamine metabolism.

AB - 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 (TCA), 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 regards 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, though 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 metabolise glutamine revealed marked differences in the expression of glutaminase isoforms KGA and CAG as well as the PPAT enzyme that targets glutamine-derived nitrogen towards nucleotide synthesis. Together, this demonstrates that infection of CD4+ T cells with HIV-1 leads to considerable changes in the cellular glutamine metabolism.

KW - Journal Article

U2 - 10.1089/AID.2017.0165

DO - 10.1089/AID.2017.0165

M3 - Article

C2 - 28844150

SN - 0889-2229

JO - Aids Research and Human Retroviruses

JF - Aids Research and Human Retroviruses

ER -