Résumé
A multitude of factors affect the biological activity of nucleoside analogs (Nu), which must be phosphorylated intracellularly by cellular or viral enzymes before exerting their effects. It follows that the intracellular metabolism of nucleosides is a key event for the appearance of their biological response. In all the nucleoside series with the same sugar modification, the biological responses differ greatly according to the type of nucleobase. Nucleosides may be first converted to their corresponding 5-mononucleotides (NuMP) by cellular or viral enzymes. Some nucleosides do not show a biological response only, because they are not enzymatically transformed to the corresponding NuMP. The presence and activity of the intracellular enzymes necessary for activation of nucleoside analogs are highly dependent on host species, cell type, and stage in the cell cycle. The emergence of resistance to nucleoside analogs has been frequently attributed to a decrease or loss of activity of the first phosphorylating enzyme. Nucleotides are readily dephosphorylated in extracellular fluids and on cell surfaces by nonspecific phosphohydrolases.