Epigenetic reprogramming of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) in HIV-1-infected CEM T cells.
Sialylated glycoconjugates mediate several key lymphocyte functions. We previously reported that hyposialylation occurred in latently HIV-1-infected CEM T cells, despite the fully preserved catalytic activity of several sialyltransferases. We show now that these cells are affected by a down-regulation of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE), which leads to a dramatic decrease in the synthesis of CMP-sialic acid, the donor substrate of all sialyltransferases. The GNE gene promoter was found to be located in a CpG island with several regulatory motifs CREB, SP1, and AP-2. De novo hypermethylation of this promoter was observed in HIV-1-infected CEM cells. This phenomenon might explain some immunological disorders that persist in infected individuals despite long-term therapeutically controlled viral replication. Indeed, an overall decrease in sialic acid engraftment can affect glycoproteins, notably those in which the sialylation status is crucial to ensure homing, recirculation, and survival of lymphocytes.
INSERM U526, IFR 50, Laboratoire de Virologie, Faculté de Médecine, Nice, France.
Valerie
V
Giordanengo
Laurence
L
Ollier
Marion
M
Lanteri
Josette
J
Lesimple
Denise
D
March
Sylvain
S
Thyss
Jean-Claude
JC
Lefebvre
D002460:Cell Line; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015971:Gene Expression Regulation, Enzymologic; D020868:Gene Silencing; D015497:HIV-1 / Q000502:physiology*; D006595:Hexosamines / Q000378:metabolism; D006801:Humans; D009097:Multienzyme Complexes / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012794:Sialic Acids / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology* / Q000821:virology*
D006595:Hexosamines; D009097:Multienzyme Complexes; D012794:Sialic Acids; C482901:UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase; C002022:N-acetylmannosamine