A hypothesis relating lymphocyte phosphorylation and transport of ara-C (Cytarabine) to its antiviral activity

Abstract

A hypothesis is presented which suggests that the antiviral activity of ara-C in man is augmented by the transport of activated ara-C within circulating lymphocytes. The salient features of the hypothesis are the following. First, suggestive evidence is accumulating that ara-C is an effective antiviral agent in man against certain DNA viruses (primarily herpesviruses) after systemic administration. Secondly, ara-C is transported and directed to the site of virus infection by lymphocytes. Third, the small lymphocytes circulating in the blood of man are more active compared with several animal species in phosphorylating (activating) ara-C, and this may be the reason why ara-C is much less effective in animals. Fourth, the antiviral activity of ara-C, which seems to be greater than what might be expected from plasma level studies, may be further augmented because the ara-C is being transported intracellularly and is therefore protected from normal catabolic and excretory processes. Fifth, the non-proliferating circulating lymphocyte can carry this cytotoxic agent safely because ara-C is inhibitory only during the S- (DNA-synthetic) phase of the cell cycle. Finally then, the activated ara-C could be introduced into the virus-infected cell by either normal immunologic cell to cell contact mechanisms or by cell fusion.