Skip to main content
Top
Published in: Virology Journal 1/2010

Open Access 01-12-2010 | Review

Cellular receptor binding and entry of human papillomavirus

Authors: Tan Letian, Zhang Tianyu

Published in: Virology Journal | Issue 1/2010

Login to get access

Abstract

Human papillomaviruses (HPVs), recognized as the etiological agents for the skin, plantar, genital, and laryngopharyngeal wart, have been previously in numerous studies demonstrated to present a close link between HPV infection and certain human cancers, some putative candidates of HPV cell receptor and possible pathways of cell entry proposed. This review was to highlight the investigations and remaining questions regarding the binding and entry process.
Literature
1.
go back to reference Roden RB, Kirnbauer R, Jenson AB, Lowy DR, Schiller JT: Interaction of papillomaviruses with the cell surface. J Virol 1994, 68: 7260-7266.PubMedPubMedCentral Roden RB, Kirnbauer R, Jenson AB, Lowy DR, Schiller JT: Interaction of papillomaviruses with the cell surface. J Virol 1994, 68: 7260-7266.PubMedPubMedCentral
2.
go back to reference Evander M, Frazer IH, Payne E, Qi YM, Hengst K, McMillan NA: Identification of the alpha6 integrin as a candidate receptor for papillomaviruses. J Virol 1997, 71: 2449-2456.PubMedPubMedCentral Evander M, Frazer IH, Payne E, Qi YM, Hengst K, McMillan NA: Identification of the alpha6 integrin as a candidate receptor for papillomaviruses. J Virol 1997, 71: 2449-2456.PubMedPubMedCentral
3.
go back to reference Patterson NA, Smith JL, Ozbun MA: Human papillomavirus type 31b infection of human keratinocytes does not require heparan sulfate. J Virol 2005, 79: 6838-6847. 10.1128/JVI.79.11.6838-6847.2005PubMedPubMedCentralCrossRef Patterson NA, Smith JL, Ozbun MA: Human papillomavirus type 31b infection of human keratinocytes does not require heparan sulfate. J Virol 2005, 79: 6838-6847. 10.1128/JVI.79.11.6838-6847.2005PubMedPubMedCentralCrossRef
5.
go back to reference Wang HK, Duffy AA, Broker TR, Chow LT: Robust production and passaging of infectious HPV in squamous epithelium of primary human keratinocytes. Genes Dev 2009, 23: 181-194. 10.1101/gad.1735109PubMedPubMedCentralCrossRef Wang HK, Duffy AA, Broker TR, Chow LT: Robust production and passaging of infectious HPV in squamous epithelium of primary human keratinocytes. Genes Dev 2009, 23: 181-194. 10.1101/gad.1735109PubMedPubMedCentralCrossRef
6.
go back to reference Chow LT, Duffy AA, Wang HK, Broker TR: A highly efficient system to produce infectious human papillomavirus: Elucidation of natural virus-host interactions. Cell Cycle 2009, 8: 1319-1323.PubMedCrossRef Chow LT, Duffy AA, Wang HK, Broker TR: A highly efficient system to produce infectious human papillomavirus: Elucidation of natural virus-host interactions. Cell Cycle 2009, 8: 1319-1323.PubMedCrossRef
7.
go back to reference Muller M, Gissmann L, Cristiano RJ, Sun XY, Frazer IH, Jenson AB, Alonso A, Zentgraf H, Zhou J: Papillomavirus capsid binding and uptake by cells from different tissues and species. J Virol 1995, 69: 948-954.PubMedPubMedCentral Muller M, Gissmann L, Cristiano RJ, Sun XY, Frazer IH, Jenson AB, Alonso A, Zentgraf H, Zhou J: Papillomavirus capsid binding and uptake by cells from different tissues and species. J Virol 1995, 69: 948-954.PubMedPubMedCentral
8.
go back to reference Volpers C, Unckell F, Schirmacher P, Streeck RE, Sapp M: Binding and internalization of human papillomavirus type 33 virus-like particles by eukaryotic cells. J Virol 1995, 69: 3258-3264.PubMedPubMedCentral Volpers C, Unckell F, Schirmacher P, Streeck RE, Sapp M: Binding and internalization of human papillomavirus type 33 virus-like particles by eukaryotic cells. J Virol 1995, 69: 3258-3264.PubMedPubMedCentral
9.
go back to reference Qi YM, Peng SW, Hengst K, Evander M, Park DS, Zhou J, Frazer IH: Epithelial cells display separate receptors for papillomavirus VLPs and for soluble L1 capsid protein. Virology 1996, 216: 35-45. 10.1006/viro.1996.0032PubMedCrossRef Qi YM, Peng SW, Hengst K, Evander M, Park DS, Zhou J, Frazer IH: Epithelial cells display separate receptors for papillomavirus VLPs and for soluble L1 capsid protein. Virology 1996, 216: 35-45. 10.1006/viro.1996.0032PubMedCrossRef
10.
go back to reference McMillan NA, Payne E, Frazer IH, Evander M: Expression of the alpha6 integrin confers papillomavirus binding upon receptor-negative B-cells. Virology 1999, 261: 271-279. 10.1006/viro.1999.9825PubMedCrossRef McMillan NA, Payne E, Frazer IH, Evander M: Expression of the alpha6 integrin confers papillomavirus binding upon receptor-negative B-cells. Virology 1999, 261: 271-279. 10.1006/viro.1999.9825PubMedCrossRef
11.
go back to reference Yoon CS, Kim KD, Park SN, Cheong SW: alpha(6) Integrin is the main receptor of human papillomavirus type 16 VLP. Biochem Biophys Res Commun 2001, 283: 668-673. 10.1006/bbrc.2001.4838PubMedCrossRef Yoon CS, Kim KD, Park SN, Cheong SW: alpha(6) Integrin is the main receptor of human papillomavirus type 16 VLP. Biochem Biophys Res Commun 2001, 283: 668-673. 10.1006/bbrc.2001.4838PubMedCrossRef
12.
go back to reference Giancotti FG, Stepp MA, Suzuki S, Engvall E, Ruoslahti E: Proteolytic processing of endogenous and recombinant beta 4 integrin subunit. J Cell Biol 1992, 118: 951-959. 10.1083/jcb.118.4.951PubMedCrossRef Giancotti FG, Stepp MA, Suzuki S, Engvall E, Ruoslahti E: Proteolytic processing of endogenous and recombinant beta 4 integrin subunit. J Cell Biol 1992, 118: 951-959. 10.1083/jcb.118.4.951PubMedCrossRef
13.
go back to reference Kajiji S, Tamura RN, Quaranta V: A novel integrin (alpha E beta 4) from human epithelial cells suggests a fourth family of integrin adhesion receptors. EMBO J 1989, 8: 673-680.PubMedPubMedCentral Kajiji S, Tamura RN, Quaranta V: A novel integrin (alpha E beta 4) from human epithelial cells suggests a fourth family of integrin adhesion receptors. EMBO J 1989, 8: 673-680.PubMedPubMedCentral
14.
go back to reference Kurpakus MA, Quaranta V, Jones JC: Surface relocation of alpha 6 beta 4 integrins and assembly of hemidesmosomes in an in vitro model of wound healing. J Cell Biol 1991, 115: 1737-1750. 10.1083/jcb.115.6.1737PubMedCrossRef Kurpakus MA, Quaranta V, Jones JC: Surface relocation of alpha 6 beta 4 integrins and assembly of hemidesmosomes in an in vitro model of wound healing. J Cell Biol 1991, 115: 1737-1750. 10.1083/jcb.115.6.1737PubMedCrossRef
16.
go back to reference Sonnenberg A, Calafat J, Janssen H, Daams H, Raaij-Helmer LM, Falcioni R, Kennel SJ, Aplin JD, Baker J, Loizidou M, Garrod D: Integrin alpha 6/beta 4 complex is located in hemidesmosomes, suggesting a major role in epidermal cell-basement membrane adhesion. J Cell Biol 1991, 113: 907-917. 10.1083/jcb.113.4.907PubMedCrossRef Sonnenberg A, Calafat J, Janssen H, Daams H, Raaij-Helmer LM, Falcioni R, Kennel SJ, Aplin JD, Baker J, Loizidou M, Garrod D: Integrin alpha 6/beta 4 complex is located in hemidesmosomes, suggesting a major role in epidermal cell-basement membrane adhesion. J Cell Biol 1991, 113: 907-917. 10.1083/jcb.113.4.907PubMedCrossRef
17.
go back to reference Selinka HC, Giroglou T, Nowak T, Christensen ND, Sapp M: Further evidence that papillomavirus capsids exist in two distinct conformations. J Virol 2003, 77: 12961-12967. 10.1128/JVI.77.24.12961-12967.2003PubMedPubMedCentralCrossRef Selinka HC, Giroglou T, Nowak T, Christensen ND, Sapp M: Further evidence that papillomavirus capsids exist in two distinct conformations. J Virol 2003, 77: 12961-12967. 10.1128/JVI.77.24.12961-12967.2003PubMedPubMedCentralCrossRef
18.
go back to reference Knappe M, Bodevin S, Selinka HC, Spillmann D, Streeck RE, Chen XS, Lindahl U, Sapp M: Surface-exposed amino acid residues of HPV16 L1 protein mediating interaction with cell surface heparan sulfate. J Biol Chem 2007, 282: 27913-27922. 10.1074/jbc.M705127200PubMedCrossRef Knappe M, Bodevin S, Selinka HC, Spillmann D, Streeck RE, Chen XS, Lindahl U, Sapp M: Surface-exposed amino acid residues of HPV16 L1 protein mediating interaction with cell surface heparan sulfate. J Biol Chem 2007, 282: 27913-27922. 10.1074/jbc.M705127200PubMedCrossRef
19.
go back to reference Joyce JG, Tung JS, Przysiecki CT, Cook JC, Lehman ED, Sands JA, Jansen KU, Keller PM: The L1 major capsid protein of human papillomavirus type 11 recombinant virus-like particles interacts with heparin and cell-surface glycosaminoglycans on human keratinocytes. J Biol Chem 1999, 274: 5810-5822. 10.1074/jbc.274.9.5810PubMedCrossRef Joyce JG, Tung JS, Przysiecki CT, Cook JC, Lehman ED, Sands JA, Jansen KU, Keller PM: The L1 major capsid protein of human papillomavirus type 11 recombinant virus-like particles interacts with heparin and cell-surface glycosaminoglycans on human keratinocytes. J Biol Chem 1999, 274: 5810-5822. 10.1074/jbc.274.9.5810PubMedCrossRef
20.
go back to reference Giroglou T, Florin L, Schafer F, Streeck RE, Sapp M: Human papillomavirus infection requires cell surface heparan sulfate. J Virol 2001, 75: 1565-1570. 10.1128/JVI.75.3.1565-1570.2001PubMedPubMedCentralCrossRef Giroglou T, Florin L, Schafer F, Streeck RE, Sapp M: Human papillomavirus infection requires cell surface heparan sulfate. J Virol 2001, 75: 1565-1570. 10.1128/JVI.75.3.1565-1570.2001PubMedPubMedCentralCrossRef
21.
go back to reference Combita AL, Touze A, Bousarghin L, Sizaret PY, Munoz N, Coursaget P: Gene transfer using human papillomavirus pseudovirions varies according to virus genotype and requires cell surface heparan sulfate. FEMS Microbiol Lett 2001, 204: 183-188. 10.1111/j.1574-6968.2001.tb10883.xPubMedCrossRef Combita AL, Touze A, Bousarghin L, Sizaret PY, Munoz N, Coursaget P: Gene transfer using human papillomavirus pseudovirions varies according to virus genotype and requires cell surface heparan sulfate. FEMS Microbiol Lett 2001, 204: 183-188. 10.1111/j.1574-6968.2001.tb10883.xPubMedCrossRef
22.
go back to reference Selinka HC, Giroglou T, Sapp M: Analysis of the infectious entry pathway of human papillomavirus type 33 pseudovirions. Virology 2002, 299: 279-287. 10.1006/viro.2001.1493PubMedCrossRef Selinka HC, Giroglou T, Sapp M: Analysis of the infectious entry pathway of human papillomavirus type 33 pseudovirions. Virology 2002, 299: 279-287. 10.1006/viro.2001.1493PubMedCrossRef
23.
go back to reference Shafti-Keramat S, Handisurya A, Kriehuber E, Meneguzzi G, Slupetzky K, Kirnbauer R: Different heparan sulfate proteoglycans serve as cellular receptors for human papillomaviruses. J Virol 2003, 77: 13125-13135. 10.1128/JVI.77.24.13125-13135.2003PubMedPubMedCentralCrossRef Shafti-Keramat S, Handisurya A, Kriehuber E, Meneguzzi G, Slupetzky K, Kirnbauer R: Different heparan sulfate proteoglycans serve as cellular receptors for human papillomaviruses. J Virol 2003, 77: 13125-13135. 10.1128/JVI.77.24.13125-13135.2003PubMedPubMedCentralCrossRef
24.
go back to reference Rommel O, Dillner J, Fligge C, Bergsdorf C, Wang X, Selinka HC, Sapp M: Heparan sulfate proteoglycans interact exclusively with conformationally intact HPV L1 assemblies: basis for a virus-like particle ELISA. J Med Virol 2005, 75: 114-121. 10.1002/jmv.20245PubMedCrossRef Rommel O, Dillner J, Fligge C, Bergsdorf C, Wang X, Selinka HC, Sapp M: Heparan sulfate proteoglycans interact exclusively with conformationally intact HPV L1 assemblies: basis for a virus-like particle ELISA. J Med Virol 2005, 75: 114-121. 10.1002/jmv.20245PubMedCrossRef
25.
go back to reference Chen XS, Garcea RL, Goldberg I, Casini G, Harrison SC: Structure of small virus-like particles assembled from the L1 protein of human papillomavirus 16. Mol Cell 2000, 5: 557-567. 10.1016/S1097-2765(00)80449-9PubMedCrossRef Chen XS, Garcea RL, Goldberg I, Casini G, Harrison SC: Structure of small virus-like particles assembled from the L1 protein of human papillomavirus 16. Mol Cell 2000, 5: 557-567. 10.1016/S1097-2765(00)80449-9PubMedCrossRef
27.
go back to reference Day PM, Thompson CD, Buck CB, Pang YY, Lowy DR, Schiller JT: Neutralization of human papillomavirus with monoclonal antibodies reveals different mechanisms of inhibition. J Virol 2007, 81: 8784-8792. 10.1128/JVI.00552-07PubMedPubMedCentralCrossRef Day PM, Thompson CD, Buck CB, Pang YY, Lowy DR, Schiller JT: Neutralization of human papillomavirus with monoclonal antibodies reveals different mechanisms of inhibition. J Virol 2007, 81: 8784-8792. 10.1128/JVI.00552-07PubMedPubMedCentralCrossRef
28.
go back to reference Carter JJ, Wipf GC, Benki SF, Christensen ND, Galloway DA: Identification of a human papillomavirus type 16-specific epitope on the C-terminal arm of the major capsid protein L1. J Virol 2003, 77: 11625-11632. 10.1128/JVI.77.21.11625-11632.2003PubMedPubMedCentralCrossRef Carter JJ, Wipf GC, Benki SF, Christensen ND, Galloway DA: Identification of a human papillomavirus type 16-specific epitope on the C-terminal arm of the major capsid protein L1. J Virol 2003, 77: 11625-11632. 10.1128/JVI.77.21.11625-11632.2003PubMedPubMedCentralCrossRef
29.
go back to reference Sibbet G, Romero-Graillet C, Meneguzzi G, Campo MS: alpha6 integrin is not the obligatory cell receptor for bovine papillomavirus type 4. J Gen Virol 2000, 81: 327-334.PubMedCrossRef Sibbet G, Romero-Graillet C, Meneguzzi G, Campo MS: alpha6 integrin is not the obligatory cell receptor for bovine papillomavirus type 4. J Gen Virol 2000, 81: 327-334.PubMedCrossRef
30.
go back to reference Johnson KM, Kines RC, Roberts JN, Lowy DR, Schiller JT, Day PM: Role of heparan sulfate in attachment to and infection of the murine female genital tract by human papillomavirus. J Virol 2009, 83: 2067-2074. 10.1128/JVI.02190-08PubMedPubMedCentralCrossRef Johnson KM, Kines RC, Roberts JN, Lowy DR, Schiller JT, Day PM: Role of heparan sulfate in attachment to and infection of the murine female genital tract by human papillomavirus. J Virol 2009, 83: 2067-2074. 10.1128/JVI.02190-08PubMedPubMedCentralCrossRef
31.
go back to reference Mudhakir D, Harashima H: Learning from the viral journey: how to enter cells and how to overcome intracellular barriers to reach the nucleus. AAPS J 2009, 11: 65-77. 10.1208/s12248-009-9080-9PubMedPubMedCentralCrossRef Mudhakir D, Harashima H: Learning from the viral journey: how to enter cells and how to overcome intracellular barriers to reach the nucleus. AAPS J 2009, 11: 65-77. 10.1208/s12248-009-9080-9PubMedPubMedCentralCrossRef
32.
go back to reference Sieczkarski SB, Whittaker GR: Dissecting virus entry via endocytosis. J Gen Virol 2002, 83: 1535-1545.PubMedCrossRef Sieczkarski SB, Whittaker GR: Dissecting virus entry via endocytosis. J Gen Virol 2002, 83: 1535-1545.PubMedCrossRef
33.
go back to reference Day PM, Lowy DR, Schiller JT: Papillomaviruses infect cells via a clathrin-dependent pathway. Virology 2003, 307: 1-11. 10.1016/S0042-6822(02)00143-5PubMedCrossRef Day PM, Lowy DR, Schiller JT: Papillomaviruses infect cells via a clathrin-dependent pathway. Virology 2003, 307: 1-11. 10.1016/S0042-6822(02)00143-5PubMedCrossRef
34.
go back to reference Bousarghin L, Touze A, Sizaret PY, Coursaget P: Human papillomavirus types 16, 31, and 58 use different endocytosis pathways to enter cells. J Virol 2003, 77: 3846-3850. 10.1128/JVI.77.6.3846-3850.2003PubMedPubMedCentralCrossRef Bousarghin L, Touze A, Sizaret PY, Coursaget P: Human papillomavirus types 16, 31, and 58 use different endocytosis pathways to enter cells. J Virol 2003, 77: 3846-3850. 10.1128/JVI.77.6.3846-3850.2003PubMedPubMedCentralCrossRef
35.
go back to reference Hindmarsh PL, Laimins LA: Mechanisms regulating expression of the HPV 31 L1 and L2 capsid proteins and pseudovirion entry. Virol J 2007, 4: 19. 10.1186/1743-422X-4-19PubMedPubMedCentralCrossRef Hindmarsh PL, Laimins LA: Mechanisms regulating expression of the HPV 31 L1 and L2 capsid proteins and pseudovirion entry. Virol J 2007, 4: 19. 10.1186/1743-422X-4-19PubMedPubMedCentralCrossRef
36.
go back to reference Smith JL, Campos SK, Ozbun MA: Human papillomavirus type 31 uses a caveolin 1- and dynamin 2-mediated entry pathway for infection of human keratinocytes. J Virol 2007, 81: 9922-9931. Laniosz V, Holthusen KA, Meneses PI: Bovine papillomavirus type 1: from clathrin to caveolin. J Virol 2008, 82:6288-6298. 10.1128/JVI.00988-07PubMedPubMedCentralCrossRef Smith JL, Campos SK, Ozbun MA: Human papillomavirus type 31 uses a caveolin 1- and dynamin 2-mediated entry pathway for infection of human keratinocytes. J Virol 2007, 81: 9922-9931. Laniosz V, Holthusen KA, Meneses PI: Bovine papillomavirus type 1: from clathrin to caveolin. J Virol 2008, 82:6288-6298. 10.1128/JVI.00988-07PubMedPubMedCentralCrossRef
37.
go back to reference Smith JL, Campos SK, Wandinger-Ness A, Ozbun MA: Caveolin-1-dependent infectious entry of human papillomavirus type 31 in human keratinocytes proceeds to the endosomal pathway for pH-dependent uncoating. J Virol 2008, 82: 9505-9512. 10.1128/JVI.01014-08PubMedPubMedCentralCrossRef Smith JL, Campos SK, Wandinger-Ness A, Ozbun MA: Caveolin-1-dependent infectious entry of human papillomavirus type 31 in human keratinocytes proceeds to the endosomal pathway for pH-dependent uncoating. J Virol 2008, 82: 9505-9512. 10.1128/JVI.01014-08PubMedPubMedCentralCrossRef
38.
39.
go back to reference Abban CY, Bradbury NA, Meneses PI: HPV16 and BPV1 infection can be blocked by the dynamin inhibitor dynasore. Am J Ther 2008, 15: 304-311. 10.1097/MJT.0b013e3181754134PubMedPubMedCentralCrossRef Abban CY, Bradbury NA, Meneses PI: HPV16 and BPV1 infection can be blocked by the dynamin inhibitor dynasore. Am J Ther 2008, 15: 304-311. 10.1097/MJT.0b013e3181754134PubMedPubMedCentralCrossRef
40.
go back to reference Spoden G, Freitag K, Husmann M, Boller K, Sapp M, Lambert C, Florin L: Clathrin- and caveolin-independent entry of human papillomavirus type 16--involvement of tetraspanin-enriched microdomains (TEMs). PLoS One 2008, 3: e3313. 10.1371/journal.pone.0003313PubMedPubMedCentralCrossRef Spoden G, Freitag K, Husmann M, Boller K, Sapp M, Lambert C, Florin L: Clathrin- and caveolin-independent entry of human papillomavirus type 16--involvement of tetraspanin-enriched microdomains (TEMs). PLoS One 2008, 3: e3313. 10.1371/journal.pone.0003313PubMedPubMedCentralCrossRef
41.
go back to reference Hemler ME: Tetraspanin proteins mediate cellular penetration, invasion, and fusion events and define a novel type of membrane microdomain. Annu Rev Cell Dev Biol 2003, 19: 397-422. 10.1146/annurev.cellbio.19.111301.153609PubMedCrossRef Hemler ME: Tetraspanin proteins mediate cellular penetration, invasion, and fusion events and define a novel type of membrane microdomain. Annu Rev Cell Dev Biol 2003, 19: 397-422. 10.1146/annurev.cellbio.19.111301.153609PubMedCrossRef
42.
go back to reference Levy S, Shoham T: Protein-protein interactions in the tetraspanin web. Physiology (Bethesda) 2005, 20: 218-224.CrossRef Levy S, Shoham T: Protein-protein interactions in the tetraspanin web. Physiology (Bethesda) 2005, 20: 218-224.CrossRef
43.
go back to reference Day PM, Lowy DR, Schiller JT: Heparan sulfate-independent cell binding and infection with furin-precleaved papillomavirus capsids. J Virol 2008, 82: 12565-12568. 10.1128/JVI.01631-08PubMedPubMedCentralCrossRef Day PM, Lowy DR, Schiller JT: Heparan sulfate-independent cell binding and infection with furin-precleaved papillomavirus capsids. J Virol 2008, 82: 12565-12568. 10.1128/JVI.01631-08PubMedPubMedCentralCrossRef
44.
go back to reference Richards RM, Lowy DR, Schiller JT, Day PM: Cleavage of the papillomavirus minor capsid protein, L2, at a furin consensus site is necessary for infection. Proc Natl Acad Sci USA 2006, 103: 1522-1527. 10.1073/pnas.0508815103PubMedPubMedCentralCrossRef Richards RM, Lowy DR, Schiller JT, Day PM: Cleavage of the papillomavirus minor capsid protein, L2, at a furin consensus site is necessary for infection. Proc Natl Acad Sci USA 2006, 103: 1522-1527. 10.1073/pnas.0508815103PubMedPubMedCentralCrossRef
45.
go back to reference Kamper N, Day PM, Nowak T, Selinka HC, Florin L, Bolscher J, Hilbig L, Schiller JT, Sapp M: A membrane-destabilizing peptide in capsid protein L2 is required for egress of papillomavirus genomes from endosomes. J Virol 2006, 80: 759-768. 10.1128/JVI.80.2.759-768.2006PubMedPubMedCentralCrossRef Kamper N, Day PM, Nowak T, Selinka HC, Florin L, Bolscher J, Hilbig L, Schiller JT, Sapp M: A membrane-destabilizing peptide in capsid protein L2 is required for egress of papillomavirus genomes from endosomes. J Virol 2006, 80: 759-768. 10.1128/JVI.80.2.759-768.2006PubMedPubMedCentralCrossRef
Metadata
Title
Cellular receptor binding and entry of human papillomavirus
Authors
Tan Letian
Zhang Tianyu
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2010
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-7-2

Other articles of this Issue 1/2010

Virology Journal 1/2010 Go to the issue