#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

The Dual Role of an ESCRT-0 Component HGS in HBV Transcription and Naked Capsid Secretion


Hepatitis B virus (HBV) is an important human pathogen. Chronic infection with HBV can lead to cirrhosis and liver cancer. While HBV infection is treatable, it remains a challenge to eradicate the virus in patients. HBV can produce various particles with different sizes and morphologies. Virions are complete particles with both nucleocapsids and surface antigen (HBsAg) envelope. In addition to DNA-containing virions, HBV produced incomplete particles, including HBsAg particles without nucleocapsids, naked capsid particles without the HBsAg envelope, and empty virions containing both HBsAg envelope and empty capsids. It remains unclear how these various HBV particles are exported from the liver. We identified many host factors known to be involved in a membrane trafficking machinery (so-called ESCRT), as well as required for HBV replication. Interestingly, aberrant expression of HGS (an ESCRT-0 factor) can inhibit HBV replication. However, unexpectedly, HGS could boost the release of naked capsids, while concurrently reduced the extracellular virions and HBsAg particles. HGS can associate and co-localize with HBV capsid protein. In summary, our work demonstrated that an appropriate level of HGS is important for HBV propagation. We entertain the possibility that HGS and other ESCRT factors may be further developed into a therapeutic treatment for hepatitis B.


Vyšlo v časopise: The Dual Role of an ESCRT-0 Component HGS in HBV Transcription and Naked Capsid Secretion. PLoS Pathog 11(10): e32767. doi:10.1371/journal.ppat.1005123
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005123

Souhrn

Hepatitis B virus (HBV) is an important human pathogen. Chronic infection with HBV can lead to cirrhosis and liver cancer. While HBV infection is treatable, it remains a challenge to eradicate the virus in patients. HBV can produce various particles with different sizes and morphologies. Virions are complete particles with both nucleocapsids and surface antigen (HBsAg) envelope. In addition to DNA-containing virions, HBV produced incomplete particles, including HBsAg particles without nucleocapsids, naked capsid particles without the HBsAg envelope, and empty virions containing both HBsAg envelope and empty capsids. It remains unclear how these various HBV particles are exported from the liver. We identified many host factors known to be involved in a membrane trafficking machinery (so-called ESCRT), as well as required for HBV replication. Interestingly, aberrant expression of HGS (an ESCRT-0 factor) can inhibit HBV replication. However, unexpectedly, HGS could boost the release of naked capsids, while concurrently reduced the extracellular virions and HBsAg particles. HGS can associate and co-localize with HBV capsid protein. In summary, our work demonstrated that an appropriate level of HGS is important for HBV propagation. We entertain the possibility that HGS and other ESCRT factors may be further developed into a therapeutic treatment for hepatitis B.


Zdroje

1. Ganem D, Prince AM (2004) Hepatitis B virus infection—natural history and clinical consequences. N Engl J Med 350: 1118–1129. 15014185

2. Ringelhan M, O'Connor T, Protzer U, Heikenwalder M (2015) The direct and indirect roles of HBV in liver cancer: prospective markers for HCC screening and potential therapeutic targets. J Pathol 235: 355–367. doi: 10.1002/path.4434 25196558

3. Thomas E, Yoneda M, Schiff ER (2015) Viral Hepatitis: Past and Future of HBV and HDV. Cold Spring Harb Perspect Med 5.

4. Raymond CK, Howald-Stevenson I, Vater CA, Stevens TH (1992) Morphological classification of the yeast vacuolar protein sorting mutants: evidence for a prevacuolar compartment in class E vps mutants. Mol Biol Cell 3: 1389–1402. 1493335

5. Hanson PI, Cashikar A (2012) Multivesicular body morphogenesis. Annu Rev Cell Dev Biol 28: 337–362. doi: 10.1146/annurev-cellbio-092910-154152 22831642

6. Katzmann DJ, Babst M, Emr SD (2001) Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I. Cell 106: 145–155. 11511343

7. Babst M, Katzmann DJ, Snyder WB, Wendland B, Emr SD (2002) Endosome-associated complex, ESCRT-II, recruits transport machinery for protein sorting at the multivesicular body. Dev Cell 3: 283–289. 12194858

8. Bache KG, Brech A, Mehlum A, Stenmark H (2003) Hrs regulates multivesicular body formation via ESCRT recruitment to endosomes. J Cell Biol 162: 435–442. 12900395

9. Wollert T, Hurley JH (2010) Molecular mechanism of multivesicular body biogenesis by ESCRT complexes. Nature 464: 864–869. doi: 10.1038/nature08849 20305637

10. Babst M, Katzmann DJ, Estepa-Sabal EJ, Meerloo T, Emr SD (2002) Escrt-III: an endosome-associated heterooligomeric protein complex required for mvb sorting. Dev Cell 3: 271–282. 12194857

11. Wollert T, Wunder C, Lippincott-Schwartz J, Hurley JH (2009) Membrane scission by the ESCRT-III complex. Nature 458: 172–177. doi: 10.1038/nature07836 19234443

12. Lata S, Schoehn G, Jain A, Pires R, Piehler J, et al. (2008) Helical structures of ESCRT-III are disassembled by VPS4. Science 321: 1354–1357. doi: 10.1126/science.1161070 18687924

13. Votteler J, Sundquist Wesley I (2013) Virus Budding and the ESCRT Pathway. Cell Host & Microbe 14: 232–241.

14. Garrus JE, von Schwedler UK, Pornillos OW, Morham SG, Zavitz KH, et al. (2001) Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding. Cell 107: 55–65. 11595185

15. Morita E, Sandrin V, McCullough J, Katsuyama A, Baci Hamilton I, et al. (2011) ESCRT-III protein requirements for HIV-1 budding. Cell Host Microbe 9: 235–242. doi: 10.1016/j.chom.2011.02.004 21396898

16. Kian Chua P, Lin MH, Shih C (2006) Potent inhibition of human Hepatitis B virus replication by a host factor Vps4. Virology 354: 1–6. 16920176

17. Watanabe T, Sorensen EM, Naito A, Schott M, Kim S, et al. (2007) Involvement of host cellular multivesicular body functions in hepatitis B virus budding. Proc Natl Acad Sci U S A 104: 10205–10210. 17551004

18. Lambert C, Doring T, Prange R (2007) Hepatitis B virus maturation is sensitive to functional inhibition of ESCRT-III, Vps4, and gamma 2-adaptin. J Virol 81: 9050–9060. 17553870

19. Stieler JT, Prange R (2014) Involvement of ESCRT-II in hepatitis B virus morphogenesis. PLoS One 9: e91279. doi: 10.1371/journal.pone.0091279 24614091

20. Tuttleman JS, Pourcel C, Summers J (1986) Formation of the pool of covalently closed circular viral DNA in hepadnavirus-infected cells. Cell 47: 451–460. 3768961

21. Shih C (2012) Chronic Hepatitis B and C. World Scientific Publishing Co Pte Ltd.

22. Gerin JL, Ford EC, Purcell RH (1975) Biochemical characterization of Australia antigen. Evidence for defective particles of hepatitis B virus. Am J Pathol 81: 651–668. 1211425

23. Kaplan PM, Ford EC, Purcell RH, Gerin JL (1976) Demonstration of subpopulations of Dane particles. J Virol 17: 885–893. 1255863

24. Sakamoto Y, Yamada G, Mizuno M, Nishihara T, Kinoyama S, et al. (1983) Full and empty particles of hepatitis B virus in hepatocytes from patients with HBsAg-positive chronic active hepatitis. Lab Invest 48: 678–682. 6855194

25. Schormann W, Kraft A, Ponsel D, Bruss V (2006) Hepatitis B virus particle formation in the absence of pregenomic RNA and reverse transcriptase. J Virol 80: 4187–4190. 16571836

26. Ning X, Nguyen D, Mentzer L, Adams C, Lee H, et al. (2011) Secretion of genome-free hepatitis B virus—single strand blocking model for virion morphogenesis of para-retrovirus. PLoS Pathog 7: e1002255. doi: 10.1371/journal.ppat.1002255 21966269

27. Luckenbaugh L, Kitrinos KM, Delaney WEt, Hu J (2015) Genome-free hepatitis B virion levels in patient sera as a potential marker to monitor response to antiviral therapy. J Viral Hepat 22: 561–570. doi: 10.1111/jvh.12361 25395045

28. Huovila AP, Eder AM, Fuller SD (1992) Hepatitis B surface antigen assembles in a post-ER, pre-Golgi compartment. J Cell Biol 118: 1305–1320. 1522109

29. Patient R, Hourioux C, Sizaret PY, Trassard S, Sureau C, et al. (2007) Hepatitis B virus subviral envelope particle morphogenesis and intracellular trafficking. J Virol 81: 3842–3851. 17267490

30. Doring T, Prange R (2014) Rab33B and its autophagic Atg5/12/16L1 effector assist in hepatitis B virus naked capsid formation and release. Cell Microbiol.

31. Bardens A, Doring T, Stieler J, Prange R (2011) Alix regulates egress of hepatitis B virus naked capsid particles in an ESCRT-independent manner. Cell Microbiol 13: 602–619. doi: 10.1111/j.1462-5822.2010.01557.x 21129143

32. Ghoujal B, Milev MP, Ajamian L, Abel K, Mouland AJ (2012) ESCRT-II's involvement in HIV-1 genomic RNA trafficking and assembly. Biol Cell 104: 706–721. doi: 10.1111/boc.201200021 22978549

33. Mizuno E, Kawahata K, Kato M, Kitamura N, Komada M (2003) STAM proteins bind ubiquitinated proteins on the early endosome via the VHS domain and ubiquitin-interacting motif. Mol Biol Cell 14: 3675–3689. 12972556

34. Kobayashi H, Tanaka N, Asao H, Miura S, Kyuuma M, et al. (2005) Hrs, a mammalian master molecule in vesicular transport and protein sorting, suppresses the degradation of ESCRT proteins signal transducing adaptor molecule 1 and 2. J Biol Chem 280: 10468–10477. 15640163

35. Nassal M (1992) 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. 1602535

36. Le Pogam S, Chua PK, Newman M, Shih C (2005) Exposure of RNA templates and encapsidation of spliced viral RNA are influenced by the arginine-rich domain of human hepatitis B virus core antigen (HBcAg 165–173). J Virol 79: 1871–1887. 15650211

37. Ning B, Shih C (2004) Nucleolar localization of human hepatitis B virus capsid protein. J Virol 78: 13653–13668. 15564475

38. Arzberger S, Hosel M, Protzer U (2010) Apoptosis of hepatitis B virus-infected hepatocytes prevents release of infectious virus. J Virol 84: 11994–12001. doi: 10.1128/JVI.00653-10 20719950

39. Shih CH, Li LS, Roychoudhury S, Ho MH (1989) In vitro propagation of human hepatitis B virus in a rat hepatoma cell line. Proc Natl Acad Sci U S A 86: 6323–6327. 2762328

40. Shih C, Yu MY, Li LS, Shih JW (1990) Hepatitis B virus propagated in a rat hepatoma cell line is infectious in a primate model. Virology 179: 871–873. 2238476

41. Roychoudhury S, Faruqi AF, Shih C (1991) Pregenomic RNA encapsidation analysis of eleven missense and nonsense polymerase mutants of human hepatitis B virus. J Virol 65: 3617–3624. 1710285

42. Lanford RE, Notvall L, Lee H, Beames B (1997) Transcomplementation of nucleotide priming and reverse transcription between independently expressed TP and RT domains of the hepatitis B virus reverse transcriptase. J Virol 71: 2996–3004. 9060659

43. Newman M, Chua PK, Tang FM, Su PY, Shih C (2009) Testing an electrostatic interaction hypothesis of hepatitis B virus capsid stability by using an in vitro capsid disassembly/reassembly system. J Virol 83: 10616–10626. doi: 10.1128/JVI.00749-09 19656897

44. Chu TH, Liou AT, Su PY, Wu HN, Shih C (2014) Nucleic acid chaperone activity associated with the arginine-rich domain of human hepatitis B virus core protein. J Virol 88: 2530–2543. doi: 10.1128/JVI.03235-13 24352445

45. Li HC, Huang EY, Su PY, Wu SY, Yang CC, et al. (2010) Nuclear export and import of human hepatitis B virus capsid protein and particles. PLoS Pathog 6: e1001162. doi: 10.1371/journal.ppat.1001162 21060813

46. Chua PK, Tang FM, Huang JY, Suen CS, Shih C (2010) Testing the balanced electrostatic interaction hypothesis of hepatitis B virus DNA synthesis by using an in vivo charge rebalance approach. J Virol 84: 2340–2351. doi: 10.1128/JVI.01666-09 20015989

47. Hirano S, Kawasaki M, Ura H, Kato R, Raiborg C, et al. (2006) Double-sided ubiquitin binding of Hrs-UIM in endosomal protein sorting. Nat Struct Mol Biol 13: 272–277. 16462748

48. Bishop N, Horman A, Woodman P (2002) Mammalian class E vps proteins recognize ubiquitin and act in the removal of endosomal protein-ubiquitin conjugates. J Cell Biol 157: 91–101. 11916981

49. Hasdemir B, Bunnett NW, Cottrell GS (2007) Hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) mediates post-endocytic trafficking of protease-activated receptor 2 and calcitonin receptor-like receptor. J Biol Chem 282: 29646–29657. 17675298

50. Raiborg C, Bremnes B, Mehlum A, Gillooly DJ, D'Arrigo A, et al. (2001) FYVE and coiled-coil domains determine the specific localisation of Hrs to early endosomes. J Cell Sci 114: 2255–2263. 11493665

51. Matusek T, Wendler F, Poles S, Pizette S, D'Angelo G, et al. (2014) The ESCRT machinery regulates the secretion and long-range activity of Hedgehog. Nature 516: 99–103. doi: 10.1038/nature13847 25471885

52. Baron M (2012) Endocytic routes to Notch activation. Semin Cell Dev Biol 23: 437–442. doi: 10.1016/j.semcdb.2012.01.008 22285298

53. Lund VK, Delotto R (2011) Regulation of Toll and Toll-like receptor signaling by the endocytic pathway. Small GTPases 2: 95–98. 21776409

54. Chanut-Delalande H, Jung AC, Baer MM, Lin L, Payre F, et al. (2010) The Hrs/Stam complex acts as a positive and negative regulator of RTK signaling during Drosophila development. PLoS One 5: e10245. doi: 10.1371/journal.pone.0010245 20422006

55. Haag J, Chubinskaya S, Aigner T (2006) Hgs physically interacts with Smad5 and attenuates BMP signaling. Exp Cell Res 312: 1153–1163. 16516194

56. Gaur NA, Hasek J, Brickner DG, Qiu H, Zhang F, et al. (2013) Vps factors are required for efficient transcription elongation in budding yeast. Genetics 193: 829–851. doi: 10.1534/genetics.112.146308 23335340

57. Irion U, St Johnston D (2007) bicoid RNA localization requires specific binding of an endosomal sorting complex. Nature 445: 554–558. 17268469

58. Snyder JC, Samson RY, Brumfield SK, Bell SD, Young MJ (2013) Functional interplay between a virus and the ESCRT machinery in archaea. Proc Natl Acad Sci U S A 110: 10783–10787. doi: 10.1073/pnas.1301605110 23754419

59. Richardson LG, Clendening EA, Sheen H, Gidda SK, White KA, et al. (2014) A unique N-terminal sequence in the Carnation Italian ringspot virus p36 replicase-associated protein interacts with the host cell ESCRT-I component Vps23. J Virol 88: 6329–6344. doi: 10.1128/JVI.03840-13 24672030

60. Barajas D, Martin IF, Pogany J, Risco C, Nagy PD (2014) Noncanonical role for the host Vps4 AAA+ ATPase ESCRT protein in the formation of Tomato bushy stunt virus replicase. PLoS Pathog 10: e1004087. doi: 10.1371/journal.ppat.1004087 24763736

61. Rusten TE, Stenmark H (2009) How do ESCRT proteins control autophagy? J Cell Sci 122: 2179–2183. doi: 10.1242/jcs.050021 19535733

62. Sir D, Tian Y, Chen WL, Ann DK, Yen TS, et al. (2010) The early autophagic pathway is activated by hepatitis B virus and required for viral DNA replication. Proc Natl Acad Sci U S A 107: 4383–4388. doi: 10.1073/pnas.0911373107 20142477

63. Tian Y, Sir D, Kuo CF, Ann DK, Ou JH (2011) Autophagy required for hepatitis B virus replication in transgenic mice. J Virol 85: 13453–13456. doi: 10.1128/JVI.06064-11 21957292

64. Strack B, Calistri A, Craig S, Popova E, Gottlinger HG (2003) AIP1/ALIX is a binding partner for HIV-1 p6 and EIAV p9 functioning in virus budding. Cell 114: 689–699. 14505569

65. von Schwedler UK, Stuchell M, Muller B, Ward DM, Chung HY, et al. (2003) The protein network of HIV budding. Cell 114: 701–713. 14505570

66. Bouamr F, Houck-Loomis BR, De Los Santos M, Casaday RJ, Johnson MC, et al. (2007) The C-terminal portion of the Hrs protein interacts with Tsg101 and interferes with human immunodeficiency virus type 1 Gag particle production. J Virol 81: 2909–2922. 17182674

67. Takahashi H, Mayers JR, Wang L, Edwardson JM, Audhya A (2015) Hrs and STAM function synergistically to bind ubiquitin-modified cargoes in vitro. Biophys J 108: 76–84. doi: 10.1016/j.bpj.2014.11.004 25564854

68. Urbe S, Sachse M, Row PE, Preisinger C, Barr FA, et al. (2003) The UIM domain of Hrs couples receptor sorting to vesicle formation. J Cell Sci 116: 4169–4179. 12953068

69. Amano Y, Yamashita Y, Kojima K, Yoshino K, Tanaka N, et al. (2011) Hrs recognizes a hydrophobic amino acid cluster in cytokine receptors during ubiquitin-independent endosomal sorting. J Biol Chem 286: 15458–15472. doi: 10.1074/jbc.M110.191924 21362618

70. Yamashita Y, Kojima K, Tsukahara T, Agawa H, Yamada K, et al. (2008) Ubiquitin-independent binding of Hrs mediates endosomal sorting of the interleukin-2 receptor beta-chain. J Cell Sci 121: 1727–1738. doi: 10.1242/jcs.024455 18445679

71. Mayers JR, Wang L, Pramanik J, Johnson A, Sarkeshik A, et al. (2013) Regulation of ubiquitin-dependent cargo sorting by multiple endocytic adaptors at the plasma membrane. Proc Natl Acad Sci U S A 110: 11857–11862. doi: 10.1073/pnas.1302918110 23818590

72. Tamai K, Tanaka N, Nakano T, Kakazu E, Kondo Y, et al. (2010) Exosome secretion of dendritic cells is regulated by Hrs, an ESCRT-0 protein. Biochem Biophys Res Commun 399: 384–390. doi: 10.1016/j.bbrc.2010.07.083 20673754

73. Tamai K, Shiina M, Tanaka N, Nakano T, Yamamoto A, et al. (2012) Regulation of hepatitis C virus secretion by the Hrs-dependent exosomal pathway. Virology 422: 377–385. doi: 10.1016/j.virol.2011.11.009 22138215

74. Cocucci E, Meldolesi J (2015) Ectosomes and exosomes: shedding the confusion between extracellular vesicles. Trends Cell Biol.

75. Wehman AM, Poggioli C, Schweinsberg P, Grant BD, Nance J (2011) The P4-ATPase TAT-5 inhibits the budding of extracellular vesicles in C. elegans embryos. Curr Biol 21: 1951–1959. doi: 10.1016/j.cub.2011.10.040 22100064

76. Yuan TT, Sahu GK, Whitehead WE, Greenberg R, Shih C (1999) 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 73: 5731–5740. 10364324

77. Mabit H, Schaller H (2000) Intracellular hepadnavirus nucleocapsids are selected for secretion by envelope protein-independent membrane binding. J Virol 74: 11472–11478. 11090143

78. Tuttleman JS, Pugh JC, Summers JW (1986) In vitro experimental infection of primary duck hepatocyte cultures with duck hepatitis B virus. J Virol 58: 17–25. 3512855

79. Milich DR, McLachlan A (1986) The nucleocapsid of hepatitis B virus is both a T-cell-independent and a T-cell-dependent antigen. Science 234: 1398–1401. 3491425

80. Milich DR, Chen M, Schodel F, Peterson DL, Jones JE, et al. (1997) Role of B cells in antigen presentation of the hepatitis B core. Proc Natl Acad Sci U S A 94: 14648–14653. 9405667

81. Yang PL, Althage A, Chung J, Chisari FV (2002) Hydrodynamic injection of viral DNA: a mouse model of acute hepatitis B virus infection. Proc Natl Acad Sci U S A 99: 13825–13830. 12374864

82. Summers J, Mason WS (1982) Replication of the genome of a hepatitis B—like virus by reverse transcription of an RNA intermediate. Cell 29: 403–415. 6180831

83. Yuan TT, Tai PC, Shih C (1999) Subtype-independent immature secretion and subtype-dependent replication deficiency of a highly frequent, naturally occurring mutation of human hepatitis B virus core antigen. J Virol 73: 10122–10128. 10559327

84. Pornillos O, Higginson DS, Stray KM, Fisher RD, Garrus JE, et al. (2003) HIV Gag mimics the Tsg101-recruiting activity of the human Hrs protein. J Cell Biol 162: 425–434. 12900394

85. Janvier K, Pelchen-Matthews A, Renaud JB, Caillet M, Marsh M, et al. (2011) The ESCRT-0 component HRS is required for HIV-1 Vpu-mediated BST-2/tetherin down-regulation. PLoS Pathog 7: e1001265. doi: 10.1371/journal.ppat.1001265 21304933

86. Lv M, Zhang B, Shi Y, Han Z, Zhang Y, et al. (2015) Identification of BST-2/tetherin-induced hepatitis B virus restriction and hepatocyte-specific BST-2 inactivation. Sci Rep 5: 11736. doi: 10.1038/srep11736 26119070

87. Yan R, Zhao X, Cai D, Liu Y, Block T, et al. (2015) Interferon-inducible Protein Tetherin Inhibits Hepatitis B Virus Virion Secretion. J Virol.

88. Aden DP, Fogel A, Plotkin S, Damjanov I, Knowles BB (1979) Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line. Nature 282: 615–616. 233137

89. Nakabayashi H, Taketa K, Miyano K, Yamane T, Sato J (1982) Growth of human hepatoma cells lines with differentiated functions in chemically defined medium. Cancer Res 42: 3858–3863. 6286115

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2015 Číslo 10
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#