Abstract
Hepatitis B viral core protein is present in the nucleus and cytoplasm of infected hepatocytes. There is a strong correlation between the intrahepatic distribution of core protein and the viral replication state and disease activity in patients with chronic hepatitis. To understand the role of core protein in the pathogenesis of HBV, we used a yeast two-hybrid system to search for cellular proteins interacting with the carboxyl terminus of core protein, as this region is involved in a number of important functions in the viral replication cycle including RNA packaging and DNA synthesis. A cDNA encoding the extreme C-terminal region of human actin-binding protein, ABP-276/278, was identified. This interaction was further confirmed both in vitro and in vivo. In addition, the extreme C-terminal region of ABP-276/278 interacted with the nearly full-length HBV core protein. Since this region is present in both the core and the precore proteins, it is likely that both core and precore proteins of HBV can interact with the C-terminal region of ABP-276/278. The minimal region of ABP-276/278 which interacted with the HBV core protein was the C-terminal 199 amino acid residues which correspond to part of the 23rd repeat, the entire 24th repeat and the intervening hinge II region in ABPs. The potential functional outcome of ABP interaction in HBV replication and its contribution to the pathological changes seen in patients with chronic HBV infection are discussed.
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References
Chu CM, Liaw YF. Intrahepatic distribution of hepatitis B surface and core antigens in chronic hepatitis B virus infection. Gastroenterology 92:220–225;1987.
Clemetson KJ. Platelet GPIb-V-IX complex. Thromb Haemost 78:266–270;1997.
Cudmore S, Reckmann I, Way M. Viral manipulations of the actin cytoskeleton. Trends Microbiol 5:142–148;1997.
Digard P, Elton D, Bishop K, Medcalf E, Weeds A, Pope B. Modulation of nuclear localization of the influenza virus nucleoprotein through interaction with actin filaments. J Virol 73:2222–2231;1999.
Dramsi S, Cossart P. Intracellular pathogens and the actin cytoskeleton. Annu Rev Cell Dev Biol 14:137–166;1998.
Eckhardt SG, Milich DR, McLachlan A. Hepatitis B virus core protein has two nuclear localization sequences in the arginine-rich carboxyl terminus. J Virol 65:575–582;1991.
Fackler OT, Kienzle N, Kremmer E, Boese A, Schramm B, Klimkait T, Kucherer C, Mueller-Lantzsch N. Association of human immunodeficiency virus Nef protein with actin is myristoylation dependent and influences its subcellular localization. Eur J Biochem 247:843–851;1997.
Gallina A, Bonelli F, Zentilin L, Rindi G, Muttini M, Milanesi G. A recombinant hepatitis B core antigen polypeptide with the protamine-like domain deleted self-assembles into capsid particles but fails to bind nucleic acids. J Virol 63:4645–4652;1989.
Garcia PD, Ou JH, Rutter WJ, Walter P. Targeting of the precore protein to the endoplasmic reticulum membrane: After signal peptide cleavage translocation can be aborted and the product released into the cytoplasm. J Cell Biol 106:1093–1104;1988.
Gietz D, St Jean A, Woods RA, Schiestl RH. Improved method for high efficiency transformation of intact yeast cells. Nucleic Acids Res 20:1425;1992.
Gorlin JB, Yamin R, Egan S, Stewart M, Stossel TP, Kwiatoowski DJ, Hartwig JH. Human endothelial actin-binding protein (ABP-280, nonmuscle filamin): A molecular leaf spring. J Cell Biol 111:1089–1105;1990.
Hatton T, Zhou S, Standring DN. RNA- and DNA-binding activities in hepatitis B virus capsid protein: A model for their roles in viral replication. J Virol 66:5232–5241;1992.
Hsu HC, Su IJ, Lai MY, Chen DS, Chang MH, Chuang SM, Sung JL. Biologic and prognostic significance of hepatocyte hepatitis B core antigen expressions in the natural course of chronic hepatitis B virus infection. J Hepatol 5:45–50;1987.
Kau JH, Ting LP. Phosphorylation of the core protein of hepatitis B virus by a 46-kilodalton serine kinase. J Virol 72:3796–3903;1998.
Lan YT, Li J, Liao WY, Ou JH. Roles of the three major phosphorylation sites of hepatitis B virus core protein in viral replication. Virology 259:342–348;1999.
Lanier LM, Volkman LE. Actin binding and nucleation byAutographa california M nucleopolyhedrovirus. Virology 243:167–177;1998.
Leedman PJ, Faulkner-Jones B, Cram DS, Harrison PJ, West J, O'Brien E, Simpson R, Coppel RL, Harrison LC. Cloning from the thyroid of a protein related to actin binding protein that is recognized by Graves' disease immunoglobulins. Proc Natl Acad Sci USA 90:5994–5998;1993.
Liao W, Ou JH. Phosphorylation and nuclear localization of the hepatitis B virus core protein: Significance of serine in the three repeated SPRRR motifs. J Virol 69:1025–1029;1995.
Liu B, Dai R, Tian CJ, Dawson L, Gorelick R, Yu XF. Interaction of the human immunodeficiency virus type 1 nucleocapsid with actin. J Virol 73:2901–2908;1999.
Liu G, Thomas L, Warren RA, Enns CA, Cunningham CC, Hartwig JH, Thomas G. Cytoskeleton protein ABP-280 directs the intracellular trafficking of furin and modulates proprotein processing in the endocytic pathway. J Cell Biol 139:1719–1733;1997.
Machida A, Ohnuma H, Tsuda F, Yoshikawa A, Hoshi Y, Tanaka T, Kishimoto S, Akahane Y, Miyakawa Y, Mayumi M. Phosphorylation in the carboxyl-terminal domain of the capsid protein of hepatitis B virus: Evaluation with a monoclonal antibody. J Virol 65:6024–6030;1991.
Mathew E, Sanderson CM, Hollinshead M, Smith GL. The extracellular domain of vaccinia virus protein B5R affects plaque phenotype, extracellular enveloped virus release, and intracellular actin tail formation. J Virol 72:2429–2438;1998.
Meyer SC, Zuerbig S, Cunningham CC, Hartwig JH, Bissell T, Gardner K, Fox JEB. Identification of the region in actin-binding protein that binds to the cytoplasmic domain of glycoprotein Ibα. J Biol Chem 272:2914–2919;1997.
Meyer SC, Sanan DA, Fox JE. Role of actin-binding protein in insertion of adhesion receptors into the membrane. J Biol Chem 273:3013–3020;1998.
Nassal M. The arginine-rich domain of the hepatitis B virus core protein is required for pregenome encapsidation and productive viral positive-strand DNA synthesis but not for virus assembly. J Virol 66:4107–4116;1992.
Nassal M, Rieger A. An intramolecular disulfide bridge between Cys-7 and Cys61 determines the structure of the secretory core gene product (e Ag) of hepatitis B virus. J Virol 67:4307–4315;1993.
Ohta Y, Stossel T, Hartwig J. Ligand-sensitive binding of actin-binding protein to immunoglobulin G Fe receptor I (FcγRI). Cell 67:275–282;1991.
Ou JH, Laub O, Rutter WJ. Hepatitis B virus gene function: The precore region targets the core antigen to cellular membranes and causes the secretion of the e antigen. Proc Natl Acad Sci USA 83:1578–1582;1986.
Ou JH, Yeh CT, Yen TSB. Transport of hepatitis B virus precore protein into the nucleus after cleavage of its signal peptide. J Virol 63:5238–5243;1989.
Ou JH. Molecular biology of hepatitis B virus e antigen. J Gastroenterol Hepatol 12:S178–187;1997.
Ravkov EV, Nichol ST, Peters CJ, Compans RW. Role of actin microfilaments in black creek canal virus morphogenesis. J Virol 72:2865–2870;1998.
Reckmann I, Higley S, Way M. The vaccinia virus F17R protein interacts with actin. FEBS Lett 409:141–146;1997.
Roper RL, Wolffe EJ, Weisberg AS, Moss B. The envelope protein encoded by the A33R gene is required for formation of actin-containing microvilli and efficient cell-to-cell spread of vaccinia virus. J Virol 72:4192–4204;1998.
Shadiack AM, Nitkin RM. Agrin induces α-actinin, filamin, and vinculin to co-localize with AChR clusters on cultured chick myotubes. J Neurobiol 22:617–628;1991.
Sharma CP, Ezzell RM, Arnaout MA. Direct interaction of filamin (ABP-280) with the β2-integrin subunit CD18. J Immunol 154:3461–3470;1995.
Takafuta T, Wu G, Murphy GF, Shapiro SS. Human β-filamin is a new protein that interacts with the cytoplasmic tail of glycoprotein Ibα. J Biol Chem 273:17531–17538;1998.
Wang J, Lee AS, Ou JH. Proteolytic conversion of hepatitis B virus e antigen precursor to end product occurs in a postendoplasmic reticulum compartment. J Virol 65:5080–5083;1991.
Wilk T, Gowen B, Fuller SD. Actin associates with the nucleocapsid domain of the human immunodeficiency virus gag polyprotein. J Virol 73:1931–1940;1999.
Wolffe EJ, Katz E, Weisberg AS, Moss B. The A34R glycoprotein gene is required for induction of specialized actin-containing microvilli and efficient cell-to-cell transmission of vaccinia virus. J Virol 71:3904–3915;1998.
Wolffe EJ, Weisberg AS, Moss B. Role for the vaccinia virus A36R outer envelope protein in the formation of virus-tipped actin-containing microvilli and cell-to-cell spread. Virology 244:20–26;1998.
Xu W, Xie Z, Chung WDW, Davie EW. A novel human actin-binding protein homologue that binds to platelet glycoprotein Ibα. Blood 92:1268–1276;1998.
Yeh CT, Liaw YF, Ou JH. The arginine-rich domain of hepatitis B virus precore and core proteins contains a signal for nuclear transport. J Virol 64:6141–6147;1990.
Yeh CT, Ou JH. Phosphorylation of hepatitis B virus precore and core proteins. J Virol 65:2327–2331;1991.
Yeh CT, Wong SW, Fung YK, Ou JH. Cell cycle regulation of nuclear localization of hepatitis B virus core protein. Proc Natl Acad Sci USA 90:6459–6463;1993.
Yu M, Summers J. A domain of the hepadnaviral capsid protein specifically required for DNA maturation and virus assembly. J Virol 65:2511–2517;1991.
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Huang, CJ., Chen, YH. & Ting, LP. Hepatitis B virus core protein interacts with the C-terminal region of actin-binding protein. J Biomed Sci 7, 160–168 (2000). https://doi.org/10.1007/BF02256623
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DOI: https://doi.org/10.1007/BF02256623