Intracellular Trafficking of HBV Particles

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2020 Sep 5

PMID 32887393

Citations 39

Authors

Bingfu Jiang

Eberhard Hildt

Affiliations

Soon will be listed here.

Abstract

The human hepatitis B virus (HBV), that is causative for more than 240 million cases of chronic liver inflammation (hepatitis), is an enveloped virus with a partially double-stranded DNA genome. After virion uptake by receptor-mediated endocytosis, the viral nucleocapsid is transported towards the nuclear pore complex. In the nuclear basket, the nucleocapsid disassembles. The viral genome that is covalently linked to the viral polymerase, which harbors a bipartite NLS, is imported into the nucleus. Here, the partially double-stranded DNA genome is converted in a minichromosome-like structure, the covalently closed circular DNA (cccDNA). The DNA virus HBV replicates via a pregenomic RNA (pgRNA)-intermediate that is reverse transcribed into DNA. HBV-infected cells release apart from the infectious viral parrticle two forms of non-infectious subviral particles (spheres and filaments), which are assembled by the surface proteins but lack any capsid and nucleic acid. In addition, naked capsids are released by HBV replicating cells. Infectious viral particles and filaments are released via multivesicular bodies; spheres are secreted by the classic constitutive secretory pathway. The release of naked capsids is still not fully understood, autophagosomal processes are discussed. This review describes intracellular trafficking pathways involved in virus entry, morphogenesis and release of (sub)viral particles.

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References

Yeh C, Liaw Y, Ou J . The arginine-rich domain of hepatitis B virus precore and core proteins contains a signal for nuclear transport. J Virol. 1990; 64(12):6141-7. PMC: 248788. DOI: 10.1128/JVI.64.12.6141-6147.1990. View

Hurtley S, Helenius A . Protein oligomerization in the endoplasmic reticulum. Annu Rev Cell Biol. 1989; 5:277-307. DOI: 10.1146/annurev.cb.05.110189.001425. View

Sells M, Chen M, Acs G . Production of hepatitis B virus particles in Hep G2 cells transfected with cloned hepatitis B virus DNA. Proc Natl Acad Sci U S A. 1987; 84(4):1005-9. PMC: 304350. DOI: 10.1073/pnas.84.4.1005. View

Gottlinger H, Dorfman T, Sodroski J, Haseltine W . Effect of mutations affecting the p6 gag protein on human immunodeficiency virus particle release. Proc Natl Acad Sci U S A. 1991; 88(8):3195-9. PMC: 51412. DOI: 10.1073/pnas.88.8.3195. View

Bayer M, Blumberg B, Werner B . Particles associated with Australia antigen in the sera of patients with leukaemia, Down's Syndrome and hepatitis. Nature. 1968; 218(5146):1057-9. DOI: 10.1038/2181057a0. View

Bartenschlager R, Schaller H . A short cis-acting sequence is required for hepatitis B virus pregenome encapsidation and sufficient for packaging of foreign RNA. EMBO J. 1990; 9(10):3389-96. PMC: 552077. DOI: 10.1002/j.1460-2075.1990.tb07540.x. View

Bottcher B, Tsuji N, Takahashi H, Dyson M, Zhao S, Crowther R . Peptides that block hepatitis B virus assembly: analysis by cryomicroscopy, mutagenesis and transfection. EMBO J. 1998; 17(23):6839-45. PMC: 1171031. DOI: 10.1093/emboj/17.23.6839. View

Macovei A, Petrareanu C, Lazar C, Florian P, Branza-Nichita N . Regulation of hepatitis B virus infection by Rab5, Rab7, and the endolysosomal compartment. J Virol. 2013; 87(11):6415-27. PMC: 3648082. DOI: 10.1128/JVI.00393-13. View

Summers J, Mason W . Replication of the genome of a hepatitis B--like virus by reverse transcription of an RNA intermediate. Cell. 1982; 29(2):403-15. DOI: 10.1016/0092-8674(82)90157-x. View

10.

Hildt E, Munz B, Saher G, Reifenberg K, Hofschneider P . The PreS2 activator MHBs(t) of hepatitis B virus activates c-raf-1/Erk2 signaling in transgenic mice. EMBO J. 2002; 21(4):525-35. PMC: 125852. DOI: 10.1093/emboj/21.4.525. View

11.

Dumortier J, Prange R . Hepatitis B virus assembly is sensitive to changes in the cytosolic S loop of the envelope proteins. Virology. 2000; 270(2):358-67. DOI: 10.1006/viro.2000.0268. View

12.

Hanson P, Cashikar A . Multivesicular body morphogenesis. Annu Rev Cell Dev Biol. 2012; 28:337-62. DOI: 10.1146/annurev-cellbio-092910-154152. View

13.

Perlman D, Berg E, OConnor P, Costello C, Hu J . Reverse transcription-associated dephosphorylation of hepadnavirus nucleocapsids. Proc Natl Acad Sci U S A. 2005; 102(25):9020-5. PMC: 1157036. DOI: 10.1073/pnas.0502138102. View

14.

Gudima S, Meier A, Dunbrack R, Taylor J, Bruss V . Two potentially important elements of the hepatitis B virus large envelope protein are dispensable for the infectivity of hepatitis delta virus. J Virol. 2007; 81(8):4343-7. PMC: 1866104. DOI: 10.1128/JVI.02478-06. View

15.

Bruss V, Ganem D . The role of envelope proteins in hepatitis B virus assembly. Proc Natl Acad Sci U S A. 1991; 88(3):1059-63. PMC: 50954. DOI: 10.1073/pnas.88.3.1059. View

16.

Bruss V, Hagelstein J, Gerhardt E, Galle P . Myristylation of the large surface protein is required for hepatitis B virus in vitro infectivity. Virology. 1996; 218(2):396-9. DOI: 10.1006/viro.1996.0209. View

17.

Eble B, Lingappa V, Ganem D . Hepatitis B surface antigen: an unusual secreted protein initially synthesized as a transmembrane polypeptide. Mol Cell Biol. 1986; 6(5):1454-63. PMC: 367670. DOI: 10.1128/mcb.6.5.1454-1463.1986. View

18.

Zhou S, Standring D . Hepatitis B virus capsid particles are assembled from core-protein dimer precursors. Proc Natl Acad Sci U S A. 1992; 89(21):10046-50. PMC: 50274. DOI: 10.1073/pnas.89.21.10046. View

19.

Rabe B, Glebe D, Kann M . Lipid-mediated introduction of hepatitis B virus capsids into nonsusceptible cells allows highly efficient replication and facilitates the study of early infection events. J Virol. 2006; 80(11):5465-73. PMC: 1472160. DOI: 10.1128/JVI.02303-05. View

20.

Diab A, Foca A, Fusil F, Lahlali T, Jalaguier P, Amirache F . Polo-like-kinase 1 is a proviral host factor for hepatitis B virus replication. Hepatology. 2017; 66(6):1750-1765. PMC: 5658273. DOI: 10.1002/hep.29236. View