O-linked N-Acetylglucosaminylation of Sp1 Inhibits the HIV-1 Promoter

The AIDS pandemic is caused by the Human Immunodeficiency Virus Type-1 (HIV-1). To date, there is neither a vaccine against HIV-1, nor a cure for AIDS available. HIV-1 gene expression and replication is regulated by the binding of cellular transcription factors to specific regulatory sites in the 5'-long terminal repeat (LTR) promoter. In this study it is demonstrated that the cell's glucose metabolism represses the replication of HIV- 1. This is based on the enzyme O-GlcNAc transferase (OGT), which is activated by increased glucose concentration and modifies proteins posttranslationally with the monosaccharide O- GlcNAc. OGT blocks the cellular transcription factor Sp1, which is essential for the replication of HIV-1 and thereby represses virus propagation. Hence, the establishment of a metabolic treatment might supplement the repertoire of antiretroviral therapies against AIDS.

Autorentext

Dr. Ramona Jochmann was born 1978 in Romania and lives since 1991 in Germany. She finished her study of biology in 2005 in Erlangen and received her PhD in 2009. During her doctorate within the Graduiertenkolleg Viruses of the Immune System she demonstrated that the cell s glucose metabolism represses the replication of HIV-1.