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  • Potential conflict of interest: Nothing to report.

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We thank Alisi et al.1 for their interested in our research on the anti–hepatitis C virus (HCV) activity of human apolipoprotein B messenger RNA–editing enzyme catalytic polypeptide (APOBEC3G, also known as hA3G),2 and believe that their consideration is valuable for our investigation. Basically, adenosine deaminases that act on RNA (ADARs) and cytidine deaminases are two generic classes of deaminases. Homology between hA3G and ADAR at neither messenger RNA nor protein level is recognized.

ADARs act at double-stranded (ds) RNA. They catalyze the A-to-I editing reaction on dsRNA, causing nucleotide substitution and dsRNA destabilization. The effect of ADARs on viruses is complicated with variability, such as ADAR concentration, viral strains, among others.3 Transgenic mice overexpressing wild-type or deaminase-deficient ADAR2 protein exhibited metabolic alterations characterized with hyperphagia and adult onset obesity;4 knockout of the ADAR gene in mice caused high lethality.5-7 Thus, ADARs might not be an ideal drug target for virus.

hA3G belongs to the family of cytidine deaminases. It acts at either RNA or DNA, and mediates hydrolytic deamination at the C4 position of the cytidine (C) or deoxycytidine (dC) base, converting C to uracil (U) (or dC to dU). hA3G inhibits replication of RNA as well as DNA viruses.8 The hA3G-mediated viral restriction is not simply via editing, and other mechanisms such as inhibition on tRNA3Lys annealing to viral RNA, or on reverse transcription, often play key roles.8 The anti-HCV activity of hA3G appeared not to be mediated through its RNA editing function.2 A proviral effect of hA3G has not been documented. Furthermore, APOBEC3 is not essential for development, survival, or fertility in mouse experiments;9 overexpression of hA3G did not alter cell growth,2 suggesting its potential as a drug target.

Zong-Gen Peng Ph.D.*, Xue-Fu You M.D.*, Jian-Dong Jiang M.D.*, * Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing, China.

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