Retroviruses under editing crossfire

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Abstract
The importance of innate intracellular immunity as a mechanism of protection against viruses is increasingly being recognized. For example, the Friend virus susceptibility 1 ( Fv1 ) gene restricts the sensitivity of mice to the murine leukaemia virus (MLV; Best et al , 1996), and the cytoplasmic body‐component tripartite‐motif 5α (TRIM5‐α) limits the susceptibility of non‐human primates to infection by the human immunodeficiency virus (HIV; Stremlau et al , 2004). Inevitably, viruses have evolved strategies to overcome these obstacles. The virion‐infectivity factor (Vif) protein of lentiviruses counters the antiviral action of the cellular enzyme apolipoprotein B mRNA‐editing enzyme catalytic‐polypeptide 3G (APOBEC3G; Sheehy et al , 2002). APOBEC3G belongs to the cytidine deaminase superfamily, the founding member of which is APOBEC1. Another well‐characterized relative is activation‐induced deaminase (AID), which is a B‐cell protein that has an essential role in antibody diversification through governing somatic hypermutation, gene conversion and class‐switch recombination at the immunoglobulin loci (Neuberger et al , 2003). APOBEC3G is expressed notably in T lymphocytes and macrophages, which are the main targets of HIV. In the absence of Vif, it is packaged into virions during viral assembly and acts during reverse transcription to deaminate deoxycytidine residues to deoxyuridine (dU) in the growing minus‐strand viral DNA (Sheehy et al , 2002; Harris et al , 2003; Lecossier et al , 2003; Mangeat et al , 2003; Zhang et al , 2003). These dU‐rich transcripts are either degraded or yield G‐to‐A hypermutated proviruses that are largely non‐functional (Fig 1). Vif …