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Journal of Virology, May 2000, p. 4721-4728, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Core Protein Phosphorylation Modulates Pregenomic RNA Encapsidation to Different Extents in Human and Duck Hepatitis B Viruses

Elena V. Gazina,1,2,* James E. Fielding,1 Bo Lin,1 and David A. Anderson1

Macfarlane Burnet Centre for Medical Research and Australian Centre for Hepatitis Virology, Fairfield 3078, Victoria, Australia,1 and D. I. Ivanovsky Institute of Virology, Academy of Medical Sciences, 123098 Moscow, Russia2

Received 28 October 1999/Accepted 24 February 2000

To clarify the role of core protein phosphorylation in pregenomic-RNA encapsidation of human and duck hepatitis B viruses (HBV and DHBV, respectively), we have examined the phosphorylation states of different forms of intracellular HBV core protein and the phenotypic effects of mutations in the phosphorylation sites of HBV and DHBV core proteins. We show that HBV core protein is phosphorylated to similar extents in the form of protein dimers and after further assembly in pregenomic RNA-containing capsids. Individual and multiple substitutions of alanine and aspartic acid for serine in the phosphorylation sites of HBV core protein resulted in site-specific and synergistic effects on RNA encapsidation, ranging from 2-fold enhancement to more than 10-fold inhibition. Core protein variants with mutations in all phosphorylation sites exhibited dominant-negative effects on RNA encapsidation by wild-type protein. The results suggest that the presence of phosphoserine at position 162 of HBV core protein is required for pregenomic-RNA encapsidation, whereas phosphoserine at position 170 optimizes the process and serine might be preferable in position 155. Examination of the pregenomic-RNA-encapsidating capacities of DHBV core protein variants, in which four phosphorylation sites were jointly mutated to alanine or aspartic acid, suggests that phosphorylation of DHBV core protein at these sites may optimize pregenomic-RNA encapsidation but that its impact is much less profound than in the case of HBV. The possible mechanisms by which RNA encapsidation may be modulated by core protein phosphorylation are discussed in the context of the observed differences between the two viruses.

* Corresponding author. Mailing address: Hepatitis Research Unit, Macfarlane Burnet Centre for Medical Research, Yarra Bend Rd., Fairfield, Victoria, Australia 3078. Phone: 61 3 9282 2236. Fax: 61 3 9282 2100. E-mail: gazina{at}burnet.edu.au.

Journal of Virology, May 2000, p. 4721-4728, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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