M H Malim|
King’s Coll London, UK
Background: The HIV Vif protein is a positive regulator of infection that is essential for virus growth in cultured T-cells. Vif has also been shown to be required for pathogenic lentivirus infections in animal model systems and is, therefore, presumed to be necessary for HIV-induced disease in infected persons. Earlier work had suggested that Vif operates by suppressing the action of human genes with natural anti-viral function. Here, the isolation of a human gene, called CEM15, that bears the hallmarks of a cellular target of Vif is discussed. Specifically, the induced expression of CEM15 in cells in which it is not normally expressed selectively inhibits the infectivity and replication of viruses that lack functional vif genes. Interestingly, CEM15 is a member of a family of approximately 9 related proteins, some of which have been shown to be cytidine deaminases. In the context of RNA or DNA, the deamination of cytidine yields uridine and, as a result, changes (or “edits”) the sequence of the nucleic acid. Other members of this enzyme family act in diverse processes such as antibody diversification or low density lipoprotein metabolism.
Conclusion: The possible consequences of CEM15-mediated cytidine deamination for HIV infection will be discussed.