Complete and Incomplete Hepatitis B Virus Particles: Formation, Function, and Application
Abstract
:1. Introduction
2. Complete and Incomplete (Subviral) HBV Particles Secreted during HBV Replication
2.1. HBsAg Spheres and Filaments (Au Antigen)
2.2. Complete Virions
2.3. Empty (Genome-Free) Virions (Enveloped Capsids)
Do Empty Virions Contain an Aberrant Core Protein, HBcrAg?
2.4. RNA Virions
3. Functional Significance of the Subviral Particles
4. Potential Applications of HBV Particles in Clinical Management
4.1. Diagnostics
4.1.1. Serum Empty Virions (HBcAg) as a Marker for Hepatic CCC DNA
4.1.2. Serum HBV RNA
4.2. Empty Virions as a Candidate for a New Generation of HBV Vaccine?
5. Summary
Acknowledgments
Author Contributions
Conflicts of Interest
References
- Hu, J.; Seeger, C. Hepadnavirus genome replication and persistence. Cold Spring Harb. Perspect. Med. 2015, 5, a021386. [Google Scholar] [CrossRef] [PubMed]
- Hu, J. Hepatitis B virus virology and replication. In Hepatitis B Virus in Human Diseases; Liaw, Y.-F., Zoulim, F., Eds.; Humana Press: New York, NY, USA; Dordrecht, The Netherlands; London, UK, 2016; pp. 1–34. [Google Scholar]
- Gerelsaikhan, T.; Tavis, J.E.; Bruss, V. Hepatitis B virus nucleocapsid envelopment does not occur without genomic DNA synthesis. J. Virol. 1996, 70, 4269–4274. [Google Scholar] [PubMed]
- Summers, J.; Mason, W.S. Replication of the genome of a hepatitis B--like virus by reverse transcription of an RNA intermediate. Cell 1982, 29, 403–415. [Google Scholar] [CrossRef]
- Perlman, D.; Hu, J. Duck hepatitis B virus virion secretion requires a double-stranded DNA genome. J. Virol. 2003, 77, 2287–2294. [Google Scholar] [CrossRef] [PubMed]
- Seeger, C.; Hu, J. Why are hepadnaviruses DNA and not RNA viruses? Trends Microbiol. 1997, 5, 447–450. [Google Scholar] [CrossRef]
- Blumberg, B.S. Australia antigen and the biology of hepatitis B. Science 1977, 197, 17–25. [Google Scholar] [CrossRef] [PubMed]
- Ning, X.; Nguyen, D.; Mentzer, L.; Adams, C.; Lee, H.; Ashley, R.; Hafenstein, S.; Hu, J. Secretion of genome-free hepatitis B virus--single strand blocking model for virion morphogenesis of para-retrovirus. PLoS Pathog. 2011, 7, e1002255. [Google Scholar] [CrossRef] [PubMed]
- Luckenbaugh, L.; Kitrinos, K.M.; Delaney, W.E.T.; Hu, J. Genome-free hepatitis B virion levels in patient sera as a potential marker to monitor response to antiviral therapy. J. Viral Hepat. 2015, 22, 561–570. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.; Shen, T.; Huang, X.; Kumar, G.R.; Chen, X.; Zeng, Z.; Zhang, R.; Chen, R.; Li, T.; Zhang, T.; et al. Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound. J. Hepatol. 2016, 65, 700–710. [Google Scholar] [CrossRef] [PubMed]
- Van Bommel, F.; Bartens, A.; Mysickova, A.; Hofmann, J.; Kruger, D.H.; Berg, T.; Edelmann, A. Serum hepatitis B virus RNA levels as an early predictor of hepatitis B envelope antigen seroconversion during treatment with polymerase inhibitors. Hepatology 2015, 61, 66–76. [Google Scholar] [CrossRef] [PubMed]
- Huang, Y.W.; Chayama, K.; Kao, J.H.; Yang, S.S. Detectability and clinical significance of serum hepatitis B virus ribonucleic acid. Hepatobiliary Surg. Nutr. 2015, 4, 197–202. [Google Scholar] [PubMed]
- Rokuhara, A.; Matsumoto, A.; Tanaka, E.; Umemura, T.; Yoshizawa, K.; Kimura, T.; Maki, N.; Kiyosawa, K. Hepatitis B virus RNA is measurable in serum and can be a new marker for monitoring lamivudine therapy. J. Gastroenterol. 2006, 41, 785–790. [Google Scholar] [CrossRef] [PubMed]
- DiMattia, M.A.; Watts, N.R.; Stahl, S.J.; Grimes, J.M.; Steven, A.C.; Stuart, D.I.; Wingfield, P.T. Antigenic switching of hepatitis B virus by alternative dimerization of the capsid protein. Structure 2013, 21, 133–142. [Google Scholar] [CrossRef] [PubMed]
- Milich, D.; Liang, T.J. Exploring the biological basis of hepatitis B e antigen in hepatitis B virus infection. Hepatology 2003, 38, 1075–1086. [Google Scholar] [CrossRef] [PubMed]
- Tuttleman, J.S.; Pourcel, C.; Summers, J. Formation of the pool of covalently closed circular viral DNA in hepadnavirus-infected cells. Cell 1986, 47, 451–460. [Google Scholar] [CrossRef]
- Gao, W.; Hu, J. Formation of hepatitis B virus covalently closed circular DNA: Removal of genome-linked protein. J. Virol. 2007, 81, 6164–6174. [Google Scholar] [CrossRef] [PubMed]
- Nassal, M. Hbv cccdna: Viral persistence reservoir and key obstacle for a cure of chronic hepatitis B. Gut 2015, 64, 1972–1984. [Google Scholar] [CrossRef] [PubMed]
- Yokosuka, O.; Omata, M.; Imazeki, F.; Okuda, K. Active and inactive replication of hepatitis B virus deoxyribonucleic acid in chronic liver disease. Gastroenterology 1985, 89, 610–616. [Google Scholar] [CrossRef]
- Reaiche, G.Y.; Le Mire, M.F.; Mason, W.S.; Jilbert, A.R. The persistence in the liver of residual duck hepatitis B virus covalently closed circular DNA is not dependent upon new viral DNA synthesis. Virology 2010, 406, 286–292. [Google Scholar] [CrossRef] [PubMed]
- Seeger, C.; Litwin, S.; Mason, W.S. Hepatitis B virus: Persistence and clearance. In Hepatitis B Virus Virology and Replication; Liaw, Y.-F., Zoulim, F., Eds.; Humana Press: New York, NY, USA; Dordrecht, The Netherlands; London, UK, 2016. [Google Scholar]
- Revill, P.; Locarnini, S. The basis for antiviral therapy: Drug targets, cross-resistance, and novel small molecule inhibitors. In Hepatitis B Virus in Human Diseases; Liaw, Y.-F., Zoulim, F., Eds.; Humana Press: New York, NY, USA; Dordrecht, The Netherlands; London, UK, 2016; pp. 303–324. [Google Scholar]
- Clark, D.N.; Hu, J. Hepatitis B virus reverse transcriptase–target of current antiviral therapy and future drug development. Antivir. Res. 2015, 123, 132–137. [Google Scholar] [CrossRef] [PubMed]
- Zu Siederdissen, C.H.; Cornberg, M.; Manns, M.P. Clinical virology: Diagnosis and virological monitoring. In Hepatitis B Virus in Human Diseases; Liaw, Y.-F., Zoulim, F., Eds.; Humana Press: New York, NY, USA; Dordrecht, The Netherlands; London, UK, 2016; pp. 205–216. [Google Scholar]
- Yang, H.C.; Kao, J.H. Looking into the crystal ball: Biomarkers for outcomes of HBV infection. Hepatol. Int. 2016, 10, 99–101. [Google Scholar] [CrossRef] [PubMed]
- Heermann, K.H.; Goldmann, U.; Schwartz, W.; Seyffarth, T.; Baumgarten, H.; Gerlich, W.H. Large surface proteins of hepatitis B virus containing the pre-s sequence. J. Virol. 1984, 52, 396–402. [Google Scholar] [PubMed]
- Watanabe, T.; Sorensen, E.M.; Naito, A.; Schott, M.; Kim, S.; Ahlquist, P. Involvement of host cellular multivesicular body functions in hepatitis B virus budding. Proc. Natl. Acad. Sci. USA 2007, 104, 10205–10210. [Google Scholar] [CrossRef] [PubMed]
- Jiang, B.; Himmelsbach, K.; Ren, H.; Boller, K.; Hildt, E. Subviral hepatitis B virus filaments, like infectious viral particles, are released via multivesicular bodies. J. Virol. 2015, 90, 3330–3341. [Google Scholar] [CrossRef] [PubMed]
- Wei, Y.; Tavis, J.E.; Ganem, D. Relationship between viral DNA synthesis and virion envelopment in hepatitis B viruses. J. Virol. 1996, 70, 6455–6458. [Google Scholar] [PubMed]
- Lambert, C.; Doring, T.; Prange, R. Hepatitis B virus maturation is sensitive to functional inhibition of ESCRT-III, Vps4, and gamma 2-adaptin. J. Virol. 2007, 81, 9050–9060. [Google Scholar] [CrossRef] [PubMed]
- Bruss, V.; Ganem, D. The role of envelope proteins in hepatitis B virus assembly. Proc. Natl. Acad. Sci. USA 1991, 88, 1059–1063. [Google Scholar] [CrossRef] [PubMed]
- Bruss, V.; Thomssen, R. Mapping a region of the large envelope protein required for hepatitis B virion maturation. J. Virol. 1994, 68, 1643–1650. [Google Scholar] [PubMed]
- Bruss, V. A short linear sequence in the pre-S domain of the large hepatitis B virus envelope protein required for virion formation. J. Virol. 1997, 71, 9350–9357. [Google Scholar] [PubMed]
- Miller, R.H.; Tran, C.T.; Robinson, W.S. Hepatitis B virus particles of plasma and liver contain viral DNA-RNA hybrid molecules. Virology 1984, 139, 53–63. [Google Scholar] [CrossRef]
- Schormann, W.; Kraft, A.; Ponsel, D.; Bruss, V. Hepatitis B virus particle formation in the absence of pregenomic RNA and reverse transcriptase. J. Virol. 2006, 80, 4187–4190. [Google Scholar] [CrossRef] [PubMed]
- Perlman, D.H.; Berg, E.A.; O'Connor, P.B.; Costello, C.E.; Hu, J. Reverse transcription-associated dephosphorylation of hepadnavirus nucleocapsids. Proc. Natl. Acad. Sci. USA 2005, 102, 9020–9025. [Google Scholar] [CrossRef] [PubMed]
- Roseman, A.M.; Berriman, J.A.; Wynne, S.A.; Butler, P.J.; Crowther, R.A. A structural model for maturation of the hepatitis B virus core. Proc. Natl. Acad. Sci. USA 2005, 102, 15821–15826. [Google Scholar] [CrossRef] [PubMed]
- Koschel, M.; Oed, D.; Gerelsaikhan, T.; Thomssen, R.; Bruss, V. Hepatitis B virus core gene mutations which block nucleocapsid envelopment. J. Virol. 2000, 74, 1–7. [Google Scholar] [CrossRef] [PubMed]
- Pairan, A.; Bruss, V. Functional surfaces of the hepatitis B virus capsid. J. Virol. 2009, 83, 11616–11623. [Google Scholar] [CrossRef] [PubMed]
- Ponsel, D.; Bruss, V. Mapping of amino acid side chains on the surface of hepatitis B virus capsids required for envelopment and virion formation. J. Virol. 2003, 77, 416–422. [Google Scholar] [CrossRef] [PubMed]
- Cui, X.; Ludgate, L.; Ning, X.; Hu, J. Maturation-associated destabilization of hepatitis B virus nucleocapsid. J. Virol. 2013, 87, 11494–11503. [Google Scholar] [CrossRef] [PubMed]
- Basagoudanavar, S.H.; Perlman, D.H.; Hu, J. Regulation of hepadnavirus reverse transcription by dynamic nucleocapsid phosphorylation. J. Virol. 2007, 81, 1641–1649. [Google Scholar] [CrossRef] [PubMed]
- Ning, X.; Basagoudanavar, S.H.; Liu, K.; Luckenbaugh, L.; Wei, D.; Wang, C.; Wei, B.; Zhao, Y.; Yan, T.; Delaney, W.; et al. Capsid phosphorylation state and hepadnavirus virion secretion. J. Virol. 2017, in press. [Google Scholar] [CrossRef] [PubMed]
- Gerin, J.L.; Ford, E.C.; Purcell, R.H. Biochemical characterization of australia antigen. Evidence for defective particles of hepatitis B virus. Am. J. Pathol. 1975, 81, 651–668. [Google Scholar] [PubMed]
- Kaplan, P.M.; Ford, E.C.; Purcell, R.H.; Gerin, J.L. Demonstration of subpopulations of dane particles. J. Virol. 1976, 17, 885–893. [Google Scholar] [PubMed]
- Sakamoto, Y.; Yamada, G.; Mizuno, M.; Nishihara, T.; Kinoyama, S.; Kobayashi, T.; Takahashi, T.; Nagashima, H. Full and empty particles of hepatitis B virus in hepatocytes from patients with HBsAG-positive chronic active hepatitis. Lab Investig. 1983, 48, 678–682. [Google Scholar] [PubMed]
- Kimura, T.; Ohno, N.; Terada, N.; Rokuhara, A.; Matsumoto, A.; Yagi, S.; Tanaka, E.; Kiyosawa, K.; Ohno, S.; Maki, N. Hepatitis B virus DNA-negative dane particles lack core protein but contain a 22-kDa precore protein without C-terminal arginine-rich domain. J. Biol. Chem. 2005, 280, 21713–21719. [Google Scholar] [CrossRef] [PubMed]
- Nguyen, D.H.; Gummuluru, S.; Hu, J. Deamination-independent inhibition of hepatitis B virus reverse transcription by APOBEC3G. J. Virol. 2007, 81, 4465–4472. [Google Scholar] [CrossRef] [PubMed]
- Ludgate, L.; Liu, K.; Luckenbaugh, L.; Streck, N.; Eng, S.; Voitenleitner, C.; Delaney, W.E.T.; Hu, J. Cell-free hepatitis B virus capsid assembly dependent on the core protein C-terminal domain and regulated by phosphorylation. J. Virol. 2016, 90, 5830–5844. [Google Scholar] [CrossRef] [PubMed]
- Hilditch, C.M.; Rogers, L.J.; Bishop, D.H. Physicochemical analysis of the hepatitis B virus core antigen produced by a baculovirus expression vector. J. Gen. Virol. 1990, 71, 2755–2759. [Google Scholar] [CrossRef] [PubMed]
- Lanford, R.E.; Notvall, L. Expression of hepatitis B virus core and precore antigens in insect cells and characterization of a core-associated kinase activity. Virology 1990, 176, 222–233. [Google Scholar] [CrossRef]
- Petit, M.A.; Pillot, J. HBc and HBe antigenicity and DNA-binding activity of major core protein p22 in hepatitis b virus core particles isolated from the cytoplasm of human liver cells. J. Virol. 1985, 53, 543–551. [Google Scholar] [PubMed]
- 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. 1989, 63, 4645–4652. [Google Scholar] [PubMed]
- Wingfield, P.; Stahl, S.; Williams, R.; Steven, A. Hepatitis core antigen produced in Escherichia coli: Subunit composition, conformational analysis, and in vitro capsid assembly. Biochemistry 1995, 34, 4919–4932. [Google Scholar] [CrossRef] [PubMed]
- Hatton, T.; Zhou, S.; Standring, D. Rna- and DNA-binding activities in hepatitis B virus capsid protein: A model for their role in viral replication. J. Virol. 1992, 66, 5232–5241. [Google Scholar] [PubMed]
- Machida, A.; Tsuda, O.; 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. 1991, 65, 6024–6030. [Google Scholar] [PubMed]
- Jansen, L.; Kootstra, N.A.; van Dort, K.A.; Takkenberg, R.B.; Reesink, H.W.; Zaaijer, H.L. Hepatitis B virus pregenomic RNA is present in virions in plasma and is associated with a response to pegylated interferon Alfa-2a and nucleos(t)ide analogues. J. Infect. Dis. 2016, 213, 224–232. [Google Scholar] [CrossRef] [PubMed]
- Su, Q.; Wang, S.F.; Chang, T.E.; Breitkreutz, R.; Hennig, H.; Takegoshi, K.; Edler, L.; Schroder, C.H. Circulating hepatitis B virus nucleic acids in chronic infection: Representation of differently polyadenylated viral transcripts during progression to nonreplicative stages. Clin. Cancer Res. 2001, 7, 2005–2015. [Google Scholar] [PubMed]
- Huang, Y.W.; Chayama, K.; Tsuge, M.; Takahashi, S.; Hatakeyama, T.; Abe, H.; Hu, J.T.; Liu, C.J.; Lai, M.Y.; Chen, D.S.; et al. Differential effects of interferon and lamivudine on serum HBV RNA inhibition in patients with chronic hepatitis B. Antivir. Ther. 2010, 15, 177–184. [Google Scholar] [CrossRef] [PubMed]
- Huang, Y.W.; Takahashi, S.; Tsuge, M.; Chen, C.L.; Wang, T.C.; Abe, H.; Hu, J.T.; Chen, D.S.; Yang, S.S.; Chayama, K.; et al. On-treatment low serum HBV RNA level predicts initial virological response in chronic hepatitis B patients receiving nucleoside analogue therapy. Antivir. Ther. 2015, 20, 369–375. [Google Scholar] [CrossRef] [PubMed]
- Yuan, T.T.; Sahu, G.K.; Whitehead, W.E.; Greenberg, R.; Shih, C. The mechanism of an immature secretion phenotype of a highly frequent naturally occurring missense mutation at codon 97 of human hepatitis B virus core antigen. J. Virol. 1999, 73, 5731–5740. [Google Scholar] [PubMed]
- Chang, S.F.; Netter, H.J.; Bruns, M.; Schneider, R.; Frolich, K.; Will, H. A new avian hepadnavirus infecting snow geese (Anser caerulescens) produces a significant fraction of virions containing single-stranded DNA. Virology 1999, 262, 39–54. [Google Scholar] [CrossRef] [PubMed]
- Greco, N.; Hayes, M.H.; Loeb, D.D. Snow goose hepatitis B virus (SGHBV) envelope and capsid proteins independently contribute to the ability of SGHBV to package capsids containing single-stranded DNA in virions. J. Virol. 2014, 88, 10705–10713. [Google Scholar] [CrossRef] [PubMed]
- Tencza, M.G.; Newbold, J.E. Heterogeneous response for a mammalian hepadnavirus infection to acyclovir: Drug-arrested intermediates of minus-strand viral DNA synthesis are enveloped and secreted from infected cells as virion-like particles. J. Med. Virol. 1997, 51, 6–16. [Google Scholar] [CrossRef]
- Maini, M.K.; Gehring, A.J. The role of innate immunity in the immunopathology and treatment of HBV infection. J. Hepatol. 2016, 64, S60–70. [Google Scholar] [CrossRef] [PubMed]
- Zlotnick, A.; Venkatakrishnan, B.; Tan, Z.; Lewellyn, E.; Turner, W.; Francis, S. Core protein: A pleiotropic keystone in the HBV lifecycle. Antivir. Res. 2015, 121, 82–93. [Google Scholar] [CrossRef] [PubMed]
- Allain, J.P.; Opare-Sem, O. Screening and diagnosis of HBV in low-income and middle-income countries. Nat. Rev. Gastroenterol. Hepatol. 2016, 13, 643–653. [Google Scholar] [CrossRef] [PubMed]
- Cornberg, M.; Wong, V.W.-S.; Locarnini, S.; Brunetto, M.; Janssen, H.L.A.; Chan, H.L.-Y. The role of quantitative hepatitis B surface antigen revisited. J. Hepatol. 2017, 66, 398–411. [Google Scholar] [CrossRef] [PubMed]
- Yang, W.; Summers, J. Integration of hepadnavirus DNA in infected liver: Evidence for a linear precursor. J. Virol. 1999, 73, 9710–9717. [Google Scholar] [PubMed]
- Summers, J.; Mason, W.S. Residual integrated viral DNA after hepadnavirus clearance by nucleoside analog therapy. Proc. Natl. Acad. Sci. USA 2004, 101, 638–640. [Google Scholar] [CrossRef] [PubMed]
- Hu, J.; Nguyen, D. Therapy for chronic hepatitis B: The earlier, the better? Trends Microbiol. 2004, 12, 431–433. [Google Scholar] [CrossRef] [PubMed]
- Mason, W.S.; Gill, U.S.; Litwin, S.; Zhou, Y.; Peri, S.; Pop, O.; Hong, M.L.; Naik, S.; Quaglia, A.; Bertoletti, A.; et al. HBV DNA integration and clonal hepatocyte expansion in chronic hepatitis B patients considered immune tolerant. Gastroenterology 2016, 151, 986–998.e4. [Google Scholar] [CrossRef] [PubMed]
- Staprans, S.; Loeb, D.D.; Ganem, D. Mutations affecting hepadnavirus plus-strand DNA synthesis dissociate primer cleavage from translocation and reveal the origin of linear viral DNA. J. Virol. 1991, 65, 1255–1262. [Google Scholar] [PubMed]
- MacNab, G.M.; Alexander, J.J.; Lecatsas, G.; Bey, E.M.; Urbanowicz, J.M. Hepatitis B surface antigen produced by a human hepatoma cell line. Br. J. Cancer 1976, 34, 509–515. [Google Scholar] [CrossRef] [PubMed]
- Knowles, B.B.; Howe, C.C.; Aden, D.P. Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science 1980, 209, 497–499. [Google Scholar] [CrossRef] [PubMed]
- Thompson, A.J.; Nguyen, T.; Iser, D.; Ayres, A.; Jackson, K.; Littlejohn, M.; Slavin, J.; Bowden, S.; Gane, E.J.; Abbott, W.; et al. Serum hepatitis B surface antigen and hepatitis B e antigen titers: Disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers. Hepatology 2010, 51, 1933–1944. [Google Scholar] [CrossRef] [PubMed]
- Tseng, T.C.; Kao, J.H. Clinical utility of quantitative HBsAG in natural history and nucleos(t)ide analogue treatment of chronic hepatitis B: New trick of old dog. J. Gastroenterol. 2013, 48, 13–21. [Google Scholar] [CrossRef] [PubMed]
- Zoulim, F.; Testoni, B.; Lebosse, F. Kinetics of intrahepatic covalently closed circular DNA and serum hepatitis B surface antigen during antiviral therapy for chronic hepatitis B: Lessons from experimental and clinical studies. Clin. Gastroenterol. Hepatol. 2013, 11, 1011–1013. [Google Scholar] [CrossRef] [PubMed]
- Torresi, J. The virological and clinical significance of mutations in the overlapping envelope and polymerase genes of hepatitis B virus. J. Clin. Virol. 2002, 25, 97–106. [Google Scholar] [CrossRef]
- Guo, J.T.; Pryce, M.; Wang, X.; Barrasa, M.I.; Hu, J.; Seeger, C. Conditional replication of duck hepatitis B virus in hepatoma cells. J. Virol. 2003, 77, 1885–1893. [Google Scholar] [CrossRef] [PubMed]
- Colonno, R.J.; Genovesi, E.V.; Medina, I.; Lamb, L.; Durham, S.K.; Huang, M.L.; Corey, L.; Littlejohn, M.; Locarnini, S.; Tennant, B.C.; et al. Long-term entecavir treatment results in sustained antiviral efficacy and prolonged life span in the woodchuck model of chronic hepatitis infection. J. Infect. Dis. 2001, 184, 1236–1245. [Google Scholar] [CrossRef] [PubMed]
- Zhu, Y.; Yamamoto, T.; Cullen, J.; Saputelli, J.; Aldrich, C.E.; Miller, D.S.; Litwin, S.; Furman, P.A.; Jilbert, A.R.; Mason, W.S. Kinetics of hepadnavirus loss from the liver during inhibition of viral DNA synthesis. J. Virol. 2001, 75, 311–322. [Google Scholar] [CrossRef] [PubMed]
- Werle-Lapostolle, B.; Bowden, S.; Locarnini, S.; Wursthorn, K.; Petersen, J.; Lau, G.; Trepo, C.; Marcellin, P.; Goodman, Z.; Delaney, W.E.T.; et al. Persistence of CCCDNA during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy. Gastroenterology 2004, 126, 1750–1758. [Google Scholar] [CrossRef] [PubMed]
- Chain, B.M.; Myers, R. Variability and conservation in hepatitis B virus core protein. BMC Microbiol. 2005, 5, 33. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kimura, T.; Rokuhara, A.; Matsumoto, A.; Yagi, S.; Tanaka, E.; Kiyosawa, K.; Maki, N. New enzyme immunoassay for detection of hepatitis B virus core antigen (HBcAG) and relation between levels of HBcAG and HBV DNA. J. Clin. Microbiol. 2003, 41, 1901–1906. [Google Scholar] [CrossRef] [PubMed]
- Kimura, T.; Rokuhara, A.; Sakamoto, Y.; Yagi, S.; Tanaka, E.; Kiyosawa, K.; Maki, N. Sensitive enzyme immunoassay for hepatitis B virus core-related antigens and their correlation to virus load. J. Clin. Microbiol. 2002, 40, 439–445. [Google Scholar] [CrossRef] [PubMed]
- Wong, D.K.; Tanaka, Y.; Lai, C.L.; Mizokami, M.; Fung, J.; Yuen, M.F. Hepatitis B virus core-related antigens as markers for monitoring chronic hepatitis B infection. J. Clin. Microbiol. 2007, 45, 3942–3947. [Google Scholar] [CrossRef] [PubMed]
- Tanaka, E.; Matsumoto, A.; Yoshizawa, K.; Maki, N. Hepatitis B core-related antigen assay is useful for monitoring the antiviral effects of nucleoside analogue therapy. Intervirology 2008, 51, 3–6. [Google Scholar] [CrossRef] [PubMed]
- Suzuki, F.; Miyakoshi, H.; Kobayashi, M.; Kumada, H. Correlation between serum hepatitis B virus core-related antigen and intrahepatic covalently closed circular DNA in chronic hepatitis B patients. J. Med. Virol. 2009, 81, 27–33. [Google Scholar] [CrossRef] [PubMed]
- Maasoumy, B.; Wiegand, S.B.; Jaroszewicz, J.; Bremer, B.; Lehmann, P.; Deterding, K.; Taranta, A.; Manns, M.P.; Wedemeyer, H.; Glebe, D.; et al. Hepatitis B core-related antigen (HBcrAG) levels in the natural history of hepatitis B virus infection in a large european cohort predominantly infected with genotypes A and D. Clin. Microbiol. Infect. 2015, 21, 606.e1–606.e10. [Google Scholar] [CrossRef] [PubMed]
- Seto, W.K.; Wong, D.H.; Chan, T.Y.; Hwang, Y.Y.; Fung, J.; Liu, K.S.; Gill, H.; Lam, Y.F.; Cheung, K.S.; Lie, A.K.; et al. Association of hepatitis B core-related antigen with hepatitis B virus reactivation in occult viral carriers undergoing high-risk immunosuppressive therapy. Am. J. Gastroenterol. 2016, 111, 1788–1795. [Google Scholar] [CrossRef] [PubMed]
- Hosaka, T.; Suzuki, F.; Kobayashi, M.; Hirakawa, M.; Kawamura, Y.; Yatsuji, H.; Sezaki, H.; Akuta, N.; Suzuki, Y.; Saitoh, S.; et al. HbcrAG is a predictor of post-treatment recurrence of hepatocellular carcinoma during antiviral therapy. Liver Int. 2010, 30, 1461–1470. [Google Scholar] [CrossRef] [PubMed]
- Matsuzaki, T.; Tatsuki, I.; Otani, M.; Akiyama, M.; Ozawa, E.; Miuma, S.; Miyaaki, H.; Taura, N.; Hayashi, T.; Okudaira, S.; et al. Significance of hepatitis B virus core-related antigen and covalently closed circular DNA levels as markers of hepatitis B virus re-infection after liver transplantation. J. Gastroenterol. Hepatol. 2013, 28, 1217–1222. [Google Scholar] [CrossRef] [PubMed]
- Tada, T.; Kumada, T.; Toyoda, H.; Kiriyama, S.; Tanikawa, M.; Hisanaga, Y.; Kanamori, A.; Kitabatake, S.; Yama, T.; Tanaka, J. HBcrAG predicts hepatocellular carcinoma development: An analysis using time-dependent receiver operating characteristics. J. Hepatol. 2016, 65, 48–56. [Google Scholar] [CrossRef] [PubMed]
- Scaglione, S.J.; Lok, A.S. Effectiveness of hepatitis B treatment in clinical practice. Gastroenterology 2012, 142, 1360–1368.e1. [Google Scholar] [CrossRef] [PubMed]
- Chevaliez, S.; Hezode, C.; Bahrami, S.; Grare, M.; Pawlotsky, J.M. Long-term hepatitis B surface antigen (HBsAG) kinetics during nucleoside/nucleotide analogue therapy: Finite treatment duration unlikely. J. Hepatol. 2013, 58, 676–683. [Google Scholar] [CrossRef] [PubMed]
- Tseng, T.C.; Liu, C.J.; Yang, H.C.; Su, T.H.; Wang, C.C.; Chen, C.L.; Kuo, S.F.; Liu, C.H.; Chen, P.J.; Chen, D.S.; et al. High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low hbv load. Gastroenterology 2012, 142, 1140–1149.e3. [Google Scholar] [CrossRef] [PubMed]
- Bertoletti, A.; Ferrari, C. Adaptive immunity in HBV infection. J. Hepatol. 2016, 64, S71–S83. [Google Scholar] [CrossRef] [PubMed]
- Carman, W.F.; Zanetti, A.R.; Karayiannis, P.; Waters, J.; Manzillo, G.; Tanzi, E.; Zuckerman, A.J.; Thomas, H.C. Vaccine-induced escape mutant of hepatitis B virus. Lancet 1990, 336, 325–329. [Google Scholar] [CrossRef]
- Lai, M.W.; Lin, T.Y.; Tsao, K.C.; Huang, C.G.; Hsiao, M.J.; Liang, K.H.; Yeh, C.T. Increased seroprevalence of HBV DNA with mutations in the S gene among individuals greater than 18 years old after complete vaccination. Gastroenterology 2012, 143, 400–407. [Google Scholar] [CrossRef] [PubMed]
- Kamili, S.; Sozzi, V.; Thompson, G.; Campbell, K.; Walker, C.M.; Locarnini, S.; Krawczynski, K. Efficacy of hepatitis B vaccine against antiviral drug-resistant hepatitis B virus mutants in the chimpanzee model. Hepatology 2009, 49, 1483–1491. [Google Scholar] [CrossRef] [PubMed]
- Lacombe, K.; Boyd, A.; Lavocat, F.; Pichoud, C.; Gozlan, J.; Miailhes, P.; Lascoux-Combe, C.; Vernet, G.; Girard, P.M.; Zoulim, F. High incidence of treatment-induced and vaccine-escape hepatitis B virus mutants among human immunodeficiency virus/hepatitis B-infected patients. Hepatology 2013, 58, 912–922. [Google Scholar] [CrossRef] [PubMed]
© 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Hu, J.; Liu, K. Complete and Incomplete Hepatitis B Virus Particles: Formation, Function, and Application. Viruses 2017, 9, 56. https://doi.org/10.3390/v9030056
Hu J, Liu K. Complete and Incomplete Hepatitis B Virus Particles: Formation, Function, and Application. Viruses. 2017; 9(3):56. https://doi.org/10.3390/v9030056
Chicago/Turabian StyleHu, Jianming, and Kuancheng Liu. 2017. "Complete and Incomplete Hepatitis B Virus Particles: Formation, Function, and Application" Viruses 9, no. 3: 56. https://doi.org/10.3390/v9030056