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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.

Reverse Transcriptase- and RNA Packaging Signal-Dependent Incorporation of APOBEC3G into Hepatitis B Virus Nucleocapsids{triangledown}

David H. Nguyen and Jianming Hu*

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, {varepsilon}. In contrast, A3G is not incorporated into empty capsids formed in the absence of RT or {varepsilon}. 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.


* Corresponding author. Mailing address: Department of Microbiology and Immunology, H107, The Pennsylvania State University, College of Medicine, 500 University Drive, Hershey, PA 17033. Phone: (717) 531-6523. Fax: (717) 531-6522. E-mail: juh13{at}psu.edu

{triangledown} Published ahead of print on 14 May 2008.


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.







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