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Journal of Virology, July 2008, p. 6852-6861, Vol. 82, No. 14
0022-538X/08/$08.00+0 doi:10.1128/JVI.00465-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033
Received 3 March 2008/ Accepted 2 May 2008
APOBEC3G (A3G) is a cytidine deaminase that can inhibit a wide range of retroviruses, including the para-retrovirus hepatitis B virus (HBV). The antiviral function of A3G depends on its incorporation into assembling viral particles. However, it remains enigmatic how A3G is specifically packaged into a variety of unrelated viruses. By adopting a native agarose gel electrophoresis assay that can specifically measure the levels of A3G incorporation into HBV nucleocapsids, we found that A3G is specifically packaged into replication-competent HBV nucleocapsids in a fashion that is dependent on both the viral reverse transcriptase (RT) and viral RNA packaging signal,
. In contrast, A3G is not incorporated into empty capsids formed in the absence of RT or
. We demonstrated that the packaged A3G was protected from protease digestion by the nucleocapsids, thus confirming its interior localization. We also showed that A3G could bind RT specifically in an RNA-independent manner, which may be responsible for mediating the specific incorporation of A3G into replication-competent nucleocapsids. Finally, we provide evidence that the N-terminal domain of A3G is required for packaging into HBV nucleocapsids.
Published ahead of print on 14 May 2008.
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