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Human immunodeficiency virus type 1 (HIV-1) gene expression and replication are regulated by the promoter/enhancer located in the U3 region of the proviral 5′ long terminal repeat (LTR). The binding of cellular transcription factors to specific regulatory sites in the 5′ LTR is a key event in the replication cycle of HIV-1. Since transcriptional activity is regulated by the posttranslational modification of transcription factors with the monosaccharide O-linked N -acetyl- d -glucosamine ( O -GlcNAc), we evaluated whether increased O -GlcNAcylation affects HIV-1 transcription. In the present study we demonstrate that treatment of HIV-1-infected lymphocytes with the O -GlcNAcylation-enhancing agent glucosamine (GlcN) repressed viral transcription in a dose-dependent manner. Overexpression of O -GlcNAc transferase (OGT), the sole known enzyme catalyzing the addition of O -GlcNAc to proteins, specifically inhibited the activity of the HIV-1 LTR promoter in different T-cell lines and in primary CD4 + T lymphocytes. Inhibition of HIV-1 LTR activity in infected T cells was most efficient (>95%) when OGT was recombinantly overexpressed prior to infection. O -GlcNAcylation of the transcription factor Sp1 and the presence of Sp1-binding sites in the LTR were found to be crucial for this inhibitory effect. From this study, we conclude that O -GlcNAcylation of Sp1 inhibits the activity of the HIV-1 LTR promoter. Modulation of Sp1 O -GlcNAcylation may play a role in the regulation of HIV-1 latency and activation and links viral replication to the glucose metabolism of the host cell. Hence, the establishment of a metabolic treatment might supplement the repertoire of antiretroviral therapies against AIDS.

Mild alkaline degradation of the proteophosphomannan (PPM) under conditions that effect beta-elimination of the residues, O-glycosidically bound on serine and threonine, release mainly mannose, glucose, mannobioses and mannotrioses with the same structures as those obtained by acetolysis of the polysaccharide component of the PPM. Methylation analysis and paper chromatography demonstrated the structural heterogeneity of the tetra-, penta- and hexasaccharide fractions containing 1,2- and 1,6-linked and 1,2,6-branched manno-oligosaccharides. Methylation analysis and acetolysis, paper chromatography and analysis of the carbohydrate composition of the oligosaccharide fractions DP 7-12 and DP 15-19 demonstrated inner core region like structures containing 1,2- and 1,6-linked mannose, 1,2,6- and 1,3,6-branchpoints and N-acetyl-D-glucosamine.

The influence of aluminium administration both on the lysosomes and on the activity of DNA-dependent enzymes in rats with intact kidney function or following partial nephrectomy was investigated. The elevation in free N-acetyl-beta-D-glucosaminidase in connection with a decrease of latent beta-NAG-level in liver, spleen and kidneys may be supposed a dose dependent aluminium damage of the lysosomes. Moreover, the decrease of free and total beta-glucuronidase in the liver and spleen could be caused by a selective inhibition of synthesis of this enzyme.

Aspartylglucosaminuria was diagnosed for the first time in two german patients. First sign of the disease was retardation of speech at the age of two years. Later on, motor and mental retardation as well as a coarse face developed. Radiological examination revealed progressive changes of the thoracic and lumbar spine with wedge-shaped vertebral bodies as well as stubby metacarpalia and cystic changes of carpalia. Coarse face developed earlier than in the finnish patients described earlier. Thin cortex of long bones and cortical thickness of metacarpalia was not found in our patients.