Background: Nucleoside transporter proteins (NTs) encoded by members of the SLC28 and SLC29 gene families contribute to nucleoside and nucleobase recycling but also modulate extracellular adenosine levels and thus adenosine-regulated metabolic targets.
Methods: We have examined the expression pattern of NT-encoding genes in human adipose tissue and we have further analysed whether the mRNA related to these genes show changes in their amounts associated with either HIV-1 infection, highly active antiretroviral therapy (HAART) or development of HIV-1-associated lipodystrophy syndrome (HALS).
Results: Human adipocytes express SLC28A1, SLC28A2 and SLC28A3 (encoding hCNT1, hCNT2 and hCNT3, respectively) and SLC29A1 and SLC29A2 (encoding hENT1 and hENT2, respectively). HIV-1 infection, prior to HAART and HALS development, is associated with the upregulation of the mRNA levels of the genes encoding hCNT1, hCNT3 and hENT2. The increase in the mRNA amounts for the former two genes may be due to the action of tumour necrosis factor-alpha (TNF-alpha), a cytokine with enhanced expression in adipose tissue following HIV-1 infection, as the effect is also observed in human adipocytes in culture after treatment with TNF-alpha. HAART and HALS development are associated with the upregulation of the mRNA levels encoding hCNT2 and hENT1, and further enhancement of hCNT1, hCNT3 and hENT2 gene expression.
Conclusions: These data suggest that selected genes of the SLC28 and SLC29 families are not only targets of HIV-1 infection, but might also contribute to the development of adipose tissue alterations leading to lipodystrophy.