The Engineering of a Novel Ligand in gH Confers to HSV an Expanded Tropism Independent of gD Activation by Its Receptors

English version České info

To enter cells, all herpesviruses use the core fusion glycoproteins gH/gL and gB, in addition to species-specific glycoproteins responsible for specific tropism, etc. In HSV, the additional glycoprotein is the essential gD. We engineered in gH a heterologous ligand to the HER2 cancer receptor. The recombinant viruses entered cells through HER2, independently of gD activation by its receptors, or despite deletion of key residues that are part of the receptors’ binding sites in gD. The ligand activated gH in cis. Cumulatively, the receptor-binding and activating functions of gD were no longer essential and were replaced by the heterologous ligand in gH. Relevance to translational medicine rests in the fact that gH can serve as a tool to retarget HSV tropism to cancer-specific receptors. This expands the toolkit for the design of fully-virulent oncolytic-HSVs.

Vyšlo v časopise: The Engineering of a Novel Ligand in gH Confers to HSV an Expanded Tropism Independent of gD Activation by Its Receptors. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004907
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004907

Souhrn

Zdroje

1. Campadelli-Fiume G, Menotti L, Avitabile E, Gianni T (2012) Viral and cellular contributions to herpes simplex virus entry into the cell. Curr Opin Virol 2 : 28–36. doi: 10.1016/j.coviro.2011.12.001 22440963

2. Connolly SA, Jackson JO, Jardetzky TS, Longnecker R (2011) Fusing structure and function: a structural view of the herpesvirus entry machinery. Nat Rev Microbiol 9 : 369–381. doi: 10.1038/nrmicro2548 21478902

3. Campadelli-Fiume G, Amasio M, Avitabile E, Cerretani A, Forghieri C, et al. (2007) The multipartite system that mediates entry of herpes simplex virus into the cell. Rev Med Virol 17 : 313–326. 17573668

4. Backovic M, DuBois RM, Cockburn JJ, Sharff AJ, Vaney MC, et al. (2010) Structure of a core fragment of glycoprotein H from pseudorabies virus in complex with antibody. Proc Natl Acad Sci U S A 107 : 22635–22640. doi: 10.1073/pnas.1011507107 21149698

5. Chowdary TK, Cairns TM, Atanasiu D, Cohen GH, Eisenberg RJ, et al. (2010) Crystal structure of the conserved herpesvirus fusion regulator complex gH-gL. Nat Struct Mol Biol 17 : 882–888. doi: 10.1038/nsmb.1837 20601960

6. Rey FA (2006) Molecular gymnastics at the herpesvirus surface. EMBO Rep 7 : 1000–1005. 17016458

7. Cocchi F, Menotti L, Mirandola P, Lopez M, Campadelli-Fiume G (1998) The ectodomain of a novel member of the immunoglobulin subfamily related to the poliovirus receptor has the attributes of a bona fide receptor for herpes simplex virus types 1 and 2 in human cells. J Virol 72 : 9992–10002. 9811737

8. Geraghty RJ, Krummenacher C, Cohen GH, Eisenberg RJ, Spear PG (1998) Entry of alphaherpesviruses mediated by poliovirus receptor-related protein 1 and poliovirus receptor. Science 280 : 1618–1620. 9616127

9. Shukla D, Liu J, Blaiklock P, Shworak NW, Bai X, et al. (1999) A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1 entry. Cell 99 : 13–22. 10520990

10. Montgomery RI, Warner MS, Lum BJ, Spear PG (1996) Herpes simplex virus-1 entry into cells mediated by a novel member of the TNF/NGF receptor family. Cell 87 : 427–436. 8898196

11. Carfi A, Willis SH, Whitbeck JC, Krummenacher C, Cohen GH, et al. (2001) Herpes simplex virus glycoprotein D bound to the human receptor HveA. Mol Cell 8 : 169–179. 11511370

12. Krummenacher C, Supekar VM, Whitbeck JC, Lazear E, Connolly SA, et al. (2005) Structure of unliganded HSV gD reveals a mechanism for receptor-mediated activation of virus entry. Embo J 24 : 4144–4153. 16292345

13. Di Giovine P, Settembre EC, Bhargava AK, Luftig MA, Lou H, et al. (2011) Structure of herpes simplex virus glycoprotein d bound to the human receptor nectin-1. PLoS Pathog 7: e1002277. doi: 10.1371/journal.ppat.1002277 21980294

14. Cocchi F, Menotti L, Di Ninni V, Lopez M, Campadelli-Fiume G (2004) The herpes simplex virus JMP mutant enters receptor-negative J cells through a novel pathway independent of the known receptors nectin1, HveA, and nectin2. J Virol 78 : 4720–4729. 15078954

15. Fusco D, Forghieri C, Campadelli-Fiume G (2005) The pro-fusion domain of herpes simplex virus glycoprotein D (gD) interacts with the gD N terminus and is displaced by soluble forms of viral receptors. Proc Natl Acad Sci U S A 102 : 9323–9328. 15972328

16. Gianni T, Amasio M, Campadelli-Fiume G (2009) Herpes simplex virus gD forms distinct complexes with fusion executors gB and gH/gL through the C-terminal profusion. J Biol Chem 284 : 17370–17382. doi: 10.1074/jbc.M109.005728 19386594

17. Avitabile E, Forghieri C, Campadelli-Fiume G (2009) Cross talk among the glycoproteins involved in herpes simplex virus entry and fusion: the interaction between gB and gH/gL does not necessarily require gD. J Virol 83 : 10752–10760. doi: 10.1128/JVI.01287-09 19656900

18. Gianni T, Salvioli S, Chesnokova LS, Hutt-Fletcher LM, Campadelli-Fiume G (2013) alphavbeta6 -⁠ and alphavbeta8-integrins serve as interchangeable receptors for HSV gH/gL to promote endocytosis and activation of membrane fusion. PLoS Pathog 9: e1003806. doi: 10.1371/journal.ppat.1003806 24367260

19. Avitabile E, Forghieri C, Campadelli-Fiume G (2007) Complexes between Herpes Simplex Virus Glycoproteins gD, gB, and gH Detected in Cells by Complementation of Split Enhanced Green Fluorescent Protein. J Virol 81 : 11532–11537. 17670828

20. Atanasiu D, Whitbeck JC, Cairns TM, Reilly B, Cohen GH, et al. (2007) Bimolecular complementation reveals that glycoproteins gB and gH/gL of herpes simplex virus interact with each other during cell fusion. Proc Natl Acad Sci U S A 104 : 18718–18723. 18003913

21. Cocchi F, Fusco D, Menotti L, Gianni T, Eisenberg RJ, et al. (2004) The soluble ectodomain of herpes simplex virus gD contains a membrane-proximal pro-fusion domain and suffices to mediate virus entry. Proc Natl Acad Sci U S A 101 : 7445–7450. 15123804

22. Atanasiu D, Saw WT, Cohen GH, Eisenberg RJ (2010) Cascade of events governing cell-cell fusion induced by herpes simplex virus glycoproteins gD, gH/gL, and gB. J Virol 84 : 12292–12299. doi: 10.1128/JVI.01700-10 20861251

23. Kwon H, Bai Q, Baek HJ, Felmet K, Burton EA, et al. (2006) Soluble V domain of Nectin-1/HveC enables entry of herpes simplex virus type 1 (HSV-1) into HSV-resistant cells by binding to viral glycoprotein D. J Virol 80 : 138–148. 16352538

24. Cattaneo R, Miest T, Shashkova EV, Barry MA (2008) Reprogrammed viruses as cancer therapeutics: targeted, armed and shielded. Nat Rev Microbiol 6 : 529–540. doi: 10.1038/nrmicro1927 18552863

25. Lichty BD, Breitbach CJ, Stojdl DF, Bell JC (2014) Going viral with cancer immunotherapy. Nat Rev Cancer 14 : 559–567. doi: 10.1038/nrc3770 24990523

26. Campadelli-Fiume G, De Giovanni C, Gatta V, Nanni P, Lollini PL, et al. (2011) Rethinking herpes simplex virus: the way to oncolytic agents. Rev Med Virol 21 : 213–226. doi: 10.1002/rmv.691 21626603

27. Russell SJ, Peng KW, Bell JC (2012) Oncolytic virotherapy. Nat Biotechnol 30 : 658–670. doi: 10.1038/nbt.2287 22781695

28. Liu BL, Robinson M, Han ZQ, Branston RH, English C, et al. (2003) ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties. Gene Ther 10 : 292–303. 12595888

29. Andtbacka RHI, Collichio FA, Amatruda T, Senzer NN, Chesney J, et al. OPTiM: A randomized phase III trial of talimogene laherparepvec (T-VEC) versus subcutaneous (SC) granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment (tx) of unresected stage IIIB/C and IV melanoma; 2013.

30. Zhou G, Roizman B (2006) Construction and properties of a herpes simplex virus 1 designed to enter cells solely via the IL-13alpha2 receptor. Proc Natl Acad Sci U S A 103 : 5508–5513. 16554374

31. Zhou G, Ye GJ, Debinski W, Roizman B (2002) Engineered herpes simplex virus 1 is dependent on IL13Ralpha2 receptor for cell entry and independent of glycoprotein D receptor interaction. Proc Natl Acad Sci USA 99 : 15124–15129. 12417744

32. Menotti L, Cerretani A, Campadelli-Fiume G. A HSV recombinant exhibiting a single chain antibody to HER2/neu enters cells through the mammary tumor receptor, independently of the gD receptors; 2006; Seattle, USA. 16699034

33. Menotti L, Cerretani A, Hengel H, Campadelli-Fiume G (2008) Construction of a fully retargeted herpes simplex virus 1 recombinant capable of entering cells solely via human epidermal growth factor receptor 2. J Virol 20 : 10153–10161. doi: 10.1128/JVI.01133-08 18684832

34. Menotti L, Nicoletti G, Gatta V, Croci S, Landuzzi L, et al. (2009) Inhibition of human tumor growth in mice by an oncolytic herpes simplex virus designed to target solely HER-2-positive cells. Proc Natl Acad Sci USA 106 : 9039–9044. doi: 10.1073/pnas.0812268106 19458262

35. Nanni P, Gatta V, Menotti L, De Giovanni C, Ianzano M, et al. (2013) Preclinical Therapy of Disseminated HER-2(+) Ovarian and Breast Carcinomas with a HER-2-Retargeted Oncolytic Herpesvirus. PLoS Pathog 9: e1003155. doi: 10.1371/journal.ppat.1003155 23382683

36. Zhou G, Roizman B (2007) Separation of receptor binding and pro-fusogenic domains of glycoprotein D of herpes simplex virus 1 into distinct interacting proteins. Proc Natl Acad Sci U S A 104 : 4142–4146. 17360490

37. Kamiyama H, Zhou G, Roizman B (2006) Herpes simplex virus 1 recombinant virions exhibiting the amino terminal fragment of urokinase-type plasminogen activator can enter cells via the cognate receptor. Gene Ther 13 : 621–629. 16292350

38. Uchida H, Chan J, Goins WF, Grandi P, Kumagai I, et al. (2010) A double mutation in glycoprotein gB compensates for ineffective gD-dependent initiation of herpes simplex virus type 1 infection. J Virol 84 : 12200–12209. doi: 10.1128/JVI.01633-10 20861246

39. Zhang KX, Kim C, Chow E, Chen IS, Jia W, et al. (2011) Targeting trastuzumab-resistant breast cancer cells with a lentivirus engineered to bind antibodies that recognize HER-2. Breast Cancer Res Treat 125 : 89–97. doi: 10.1007/s10549-010-0828-9 20232140

40. Jackson C, Browell D, Gautrey H, Tyson-Capper A (2013) Clinical Significance of HER-2 Splice Variants in Breast Cancer Progression and Drug Resistance. Int J Cell Biol 2013 : 973584. doi: 10.1155/2013/973584 23935627

41. Kubetzko S, Balic E, Waibel R, Zangemeister-Wittke U, Pluckthun A (2006) PEGylation and multimerization of the anti-p185HER-2 single chain Fv fragment 4D5: effects on tumor targeting. J Biol Chem 281 : 35186–35201. 16963450

42. Gambini E, Reisoli E, Appolloni I, Gatta V, Campadelli-Fiume G, et al. (2012) Replication-competent herpes simplex virus retargeted to HER2 as therapy for high-grade glioma. Mol Ther 20 : 994–1001. doi: 10.1038/mt.2012.22 22354378

43. Menotti L, Cerretani A, Campadelli-Fiume G (2006) A herpes simplex virus recombinant that exhibits a single-chain antibody to HER2/neu enters cells through the mammary tumor receptor, independently of the gD receptors. J Virol 80 : 5531–5539. 16699034

44. Gianni T, Cerretani A, Dubois R, Salvioli S, Blystone SS, et al. (2010) Herpes simplex virus glycoproteins H/L bind to cells independently of {alpha}V{beta}3 integrin and inhibit virus entry, and their constitutive expression restricts infection. J Virol 84 : 4013–4025. doi: 10.1128/JVI.02502-09 20147400

45. Showalter SD, Zweig M, Hampar B (1981) Monoclonal antibodies to herpes simplex virus type 1 proteins, including the immediate-early protein ICP 4. Infect Immun 34 : 684–692. 6277788

46. Gompels UA, Carss AL, Saxby C, Hancock DC, Forrester A, et al. (1991) Characterization and sequence analyses of antibody-selected antigenic variants of herpes simplex virus show a conformationally complex epitope on glycoprotein H. J Virol 65 : 2393–2401. 1707982

47. Heldwein EE, Krummenacher C (2008) Entry of herpesviruses into mammalian cells. Cell Mol Life Sci 65 : 1653–1668. doi: 10.1007/s00018-008-7570-z 18351291

48. Atanasiu D, Cairns TM, Whitbeck JC, Saw WT, Rao S, et al. (2013) Regulation of herpes simplex virus gB-induced cell-cell fusion by mutant forms of gH/gL in the absence of gD and cellular receptors. MBio 4.

49. Klupp BG, Fuchs W, Weiland E, Mettenleiter TC (1997) Pseudorabies virus glycoprotein L is necessary for virus infectivity but dispensable for virion localization of glycoprotein H. J Virol 71 : 7687–7695. 9311852

50. Klupp BG, Mettenleiter TC (1999) Glycoprotein gL-independent infectivity of pseudorabies virus is mediated by a gD-gH fusion protein. J Virol 73 : 3014–3022. 10074151

51. Cairns TM, Milne RS, Ponce-de-Leon M, Tobin DK, Cohen GH, et al. (2003) Structure-function analysis of herpes simplex virus type 1 gD and gH-gL: clues from gDgH chimeras. J Virol 77 : 6731–6742. 12767993

52. Fan Q, Longnecker R, Connolly SA (2014) Substitution of herpes simplex virus 1 entry glycoproteins with those of saimiriine herpesvirus 1 reveals a gD-gH/gL functional interaction and a region within the gD profusion domain that is critical for fusion. J Virol 88 : 6470–6482. doi: 10.1128/JVI.00465-14 24672037

53. Uchida H, Chan J, Shrivastava I, Reinhart B, Grandi P, et al. (2013) Novel mutations in gB and gH circumvent the requirement for known gD Receptors in herpes simplex virus 1 entry and cell-to-cell spread. J Virol 87 : 1430–1442. doi: 10.1128/JVI.02804-12 23152509

54. Zhou G, Roizman B (2005) Characterization of a recombinant herpes simplex virus 1 designed to enter cells via the IL13Ralpha2 receptor of malignant glioma cells. J Virol 79 : 5272–5277. 15827141

55. Laquerre S, Anderson DB, Stolz DB, Glorioso JC (1998) Recombinant herpes simplex virus type 1 engineered for targeted binding to erythropoietin receptor-bearing cells. J Virol 72 : 9683–9697. 9811702

56. Baselga J, Cortes J, Kim SB, Im SA, Hegg R, et al. (2012) Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 366 : 109–119. doi: 10.1056/NEJMoa1113216 22149875

57. Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, et al. (2012) Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet 379 : 633–640. doi: 10.1016/S0140-6736(11)61847-3 22257673

58. O'Sullivan CC, Connolly RM (2014) Pertuzumab and its accelerated approval: evolving treatment paradigms and new challenges in the management of HER2-positive breast cancer. Oncology (Williston Park) 28 : 186–194, 196. 24855725

59. Ejercito PM, Kieff ED, Roizman B (1968) Characterization of herpes simplex virus strains differing in their effects on social behaviour of infected cells. J Gen Virol 2 : 357–364. 4300104

60. Tanaka M, Kagawa H, Yamanashi Y, Sata T, Kawaguchi Y (2003) Construction of an excisable bacterial artificial chromosome containing a full-length infectious clone of herpes simplex virus type 1: viruses reconstituted from the clone exhibit wild-type properties in vitro and in vivo. J Virol 77 : 1382–1391. 12502854

61. Warming S, Costantino N, Court DL, Jenkins NA, Copeland NG (2005) Simple and highly efficient BAC recombineering using galK selection. Nucleic Acids Res 33: e36. 15731329

62. Sidhu SS, Li B, Chen Y, Fellouse FA, Eigenbrot C, et al. (2004) Phage-displayed antibody libraries of synthetic heavy chain complementarity determining regions. J Mol Biol 338 : 299–310. 15066433