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Journal of Virology, May 2009, p. 4923-4933, Vol. 83, No. 10
0022-538X/09/$08.00+0     doi:10.1128/JVI.02644-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Hepatitis B Virus Replication and Release Are Independent of Core Lysine Ubiquitination{triangledown}

Mayra L. Garcia, Rushelle Byfield, and Michael D. Robek*

Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510

Received 23 December 2008/ Accepted 18 February 2009

Ubiquitin conjugation to lysine residues regulates a variety of protein functions, including endosomal trafficking and degradation. While ubiquitin plays an important role in the release of many viruses, the requirement for direct ubiquitin conjugation to viral structural proteins is less well understood. Some viral structural proteins require ubiquitin ligase activity, but not ubiquitin conjugation, for efficient release. Recent evidence has shown that, like other viruses, hepatitis B virus (HBV) requires a ubiquitin ligase for release from the infected cell. The HBV core protein contains two lysine residues (K7 and K96), and K96 has been suggested to function as a potential ubiquitin acceptor site based on the fact that previous studies have shown that mutation of this amino acid to alanine blocks HBV release. We therefore reexamined the potential connection between core lysine ubiquitination and HBV replication, protein trafficking, and virion release. In contrast to alanine substitution, we found that mutation of K96 to arginine, which compared to alanine is more conserved but also cannot mediate ubiquitin conjugation, does not affect either virus replication or virion release. We also found that the core lysine mutants display wild-type sensitivity to the antiviral activity of interferon, which demonstrates that ubiquitination of core lysines does not mediate the interferon-induced disruption of HBV capsids. However, mutation of K96 to arginine alters the nuclear-cytoplasmic distribution of core, leading to an accumulation in the nucleolus. In summary, these studies demonstrate that although ubiquitin may regulate the HBV replication cycle, these mechanisms function independently of direct lysine ubiquitination of core protein.

* Corresponding author. Mailing address: Department of Pathology, Yale University School of Medicine, P.O. Box 208023, 310 Cedar St., LH315A, New Haven, CT 06520-8023. Phone: (203) 785-6174. Fax: (203) 785-6127. E-mail: michael.robek{at}yale.edu

{triangledown} Published ahead of print on 25 February 2009.

Journal of Virology, May 2009, p. 4923-4933, Vol. 83, No. 10
0022-538X/09/$08.00+0     doi:10.1128/JVI.02644-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Pairan, A., Bruss, V. (2009). Functional Surfaces of the Hepatitis B Virus Capsid. J. Virol. 83: 11616-11623 [Abstract] [Full Text]  


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