APOBEC3G &amp; HTLV-1: Inhibition without deamination

Klaus Strebel

doi:10.1186/1742-4690-2-37

Abstract

APOBEC3G is a cellular cytidine deaminase that was recently identified as the Vif-sensitive antiviral host factor responsible for the restriction of vif-defective HIV-1 in primary human cells and certain non-permissive T cell lines. Inhibition of HIV-1 replication is thought to be the result of APOBEC3G-induced hypermutation of the viral genome that occurs early during reverse transcription. Against this backdrop is a new report from the Uchiyama laboratory that proposes deaminase-independent restriction of HTLV-1 by APOBEC3G (Sasada et al. Retrovirology 2005, 2:32). These findings combined with recent reports of deaminase-independent inhibition of Hepatitis B virus as well as HIV-1 suggest that cytidine deaminase activity and antiviral activity may be separable functional properties of APOBEC3G.

Highlights

The identification of APOBEC3G (APO3G) in 2002 as the long elusive cellular target of the HIV viral infectivity factor (Vif) [1] has triggered an outburst of research activity that has produced in a short period of time a rather comprehensive working model for APO3G function (Fig. 1)
The details of this model are changing almost daily, it is generally believed that APO3G does not interfere with virus production from infected cells but acts at a post-entry level to prevent the productive infection of new target cells
This model is consistent with more than a decade worth of biological and genetic data demonstrating that the Vif-sensitive host factor inhibits HIV-1 infectivity when expressed in the virus-producing cell but does not inhibit infection by HIV-1 when expressed in the target cell

Summary

Introduction

The identification of APOBEC3G (APO3G) in 2002 as the long elusive cellular target of the HIV viral infectivity factor (Vif) [1] has triggered an outburst of research activity that has produced in a short period of time a rather comprehensive working model for APO3G function (Fig. 1). Hypermutation of the viral genome at that stage of the viral replication cycle is thought to either result in mutational inactivation of the viral genome – ensuing in the production of defective virions in the replication cycle – or to trigger degradation of the viral genome in the target cell by activating a host DNA repair mechanism resulting in abortive infection (reviewed in [3]).

Results

Conclusion