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International Journal of
Progress in Hematology
HEMATOLOGY
APOBEC Family Proteins: Novel Antiviral Innate Immunity
Akifumi Takaori-Kondo
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Received January 10, 2006; accepted January 31, 2006
Abstract
APOBEC3G has been identied as an antihuman immunodeciency virus type 1 (HIV-1) host factor that belongs to the APOBEC superfamily of cytidine deaminases. It deaminates cytidine to uridine in nascent minus-strand viral DNA, inducing G-to-A hypermutation in the plus-strand DNA of HIV-1.The accumulating evidence demonstrates that APOBEC family proteins also have an antiviral activity against a wide variety of viruses, including not only retroviruses but also other types of viruses, and that each virus seems to have its own strategy for escaping from APOBEC proteins. These results suggest that the APOBEC3 family plays an important role in antiviral host defense as an innate immunity. Recent progress in research on APOBEC family proteins is reviewed.
Int J Hematol. 2006;83:213-216. doi: 10.1532/IJH97.060062006 The Japanese Society of Hematology
Key words: APOBEC; Human immunodeficiency virus; Hepatitis B virus; Cytidine deaminase; Innate immunity; Retrotransposon
1. Introduction
Human immunodeciency virus type 1 (HIV-1) Vif protein plays an essential role in the viral life cycle [1]. However, its functional mechanism had been unclear until APOBEC3G (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G) was identied as an antiviral host factor [2]. APOBEC3G belongs to the APOBEC superfamily of cytidine deaminases, which also includes APOBEC1, APOBEC2, APOBEC3 (A to F), and activation-induced cytidine deaminase (AID) [3]. APOBEC3G deaminates dC to dU in nascent viral DNA during reverse transcription, resulting in the destruction of viral DNA by the DNA-repair mechanism and G-to-A hypermutation in the plus-strand DNA, leading to inhibition of viral replication [4-7]. HIV-1 Vif antagonizes APOBEC3G via the ubiquitin-proteasome pathway [8-10]. Details of these processes are discussed in other articles in this issue. Several lines of studies have revealed that other members of the APOBEC family also have antiviral activity against HIV-1, although the sensitivity to the Vif protein varies among the molecules [11]. Further-
Correspondence and reprint requests: Akifumi Takaori-Kondo, Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaracho, Sakyo-ku, Kyoto 606-8507, Japan; 81-75-751-3152; fax: 81-75-751-4963 (e-mail: [email protected]).
more, the spectrum of the antiviral function of the APOBEC family...