The APOBEC (acronym for apolipoprotein B editing catalytic polypeptide)family of cytidine deaminases are widely distributed in the biological world and play a central rolein diverse enzymatic pathways. Members of this family (APOBEC3G and APOBEC3F) have been recently shownto be able to restrict HIV-1 replication in physiologically relevant target cells (macrophages, lymphocytes),presumably by triggering extensive deamination of the viral RNA/DNA replication intermediates. This naturalantiretroviral host defense mechanism is counteracted by the HIV-1 protein Vif, which is able to targetAPOBECs to degrade. The so-called "Vif/APOBEC3G paradigm" has been confirmed by a growing literature.However, evidence arising from recent studies has expanded this view, showing that the replication ofother viruses is also restricted by APOBEC family members and suggesting antiviral mechanism(s) of actionunrelated to the catalytic activity of these proteins. Furthermore, evolutionary investigations on primateshave shown that APOBEC3 gene expansion might be related to an ancient adaptive selection to prevent endogenousgenetic instability, indicating an additional ancient protective role of APOBECs. This article is aimedat broadening the current knowledge about the antiviral activity of the APOBEC members and to highlightthe notion that their role(s) might be more general than previously anticipated.

Keywords: Amino Acid Sequence, Anti-HIV Agents - metabolism, Cytidine Deaminase - metabolism, Gene Products, vif - metabolism, HIV Infections - virology, HIV-1 - physiology, Molecular Sequence Data, Nucleoside Deaminases - metabolism, Repressor Proteins - metabolism, Sequence Homology, Amino Acid, Virus Replication, vif Gene Products, Human Immunodeficiency Virus