Human cytomegalovirus gH/gL/gO promotes the fusion step of entry into all cell types, whereas gH/gL/UL128-131 broadens virus tropism through a distinct mechanism

Journal of Virology

Volumn 89, Issue 17, 2015, Pages 8999-9009

  Zhou, Momei ^a   Lanchy, Jean Marc ^a   Ryckman, Brent J ^a  

^a UNIVERSITY OF MONTANA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HYBRID PROTEIN; MACROGOL; GLYCOPROTEIN H, CYTOMEGALOVIRUS; GLYCOPROTEIN O, CYTOMEGALOVIRUS; MACROGOL DERIVATIVE; MEMBRANE PROTEIN; UL115 PROTEIN, HUMAN HERPESVIRUS 5; UL128 PROTEIN, HUMAN CYTOMEGALOVIRUS; UL130 PROTEIN, HUMAN CYTOMEGALOVIRUS; VIRUS ENVELOPE PROTEIN;

ARTICLE; CONTROLLED STUDY; ENDOTHELIUM CELL; EPITHELIUM CELL; EPSTEIN BARR VIRUS; FIBROBLAST; HUMAN; HUMAN CELL; HUMAN CYTOMEGALOVIRUS; NONHUMAN; PRIORITY JOURNAL; VIRAL TROPISM; VIRION; VIRUS ENTRY; VIRUS ENVELOPE; VIRUS NEUTRALIZATION; VIRUS REPLICATION; VIRUS STRAIN; CELL LINE; CYTOMEGALOVIRUS; CYTOMEGALOVIRUS INFECTION; GENETICS; METABOLISM; MUTATION; PATHOGENICITY; PATHOLOGY; VIROLOGY;

HERPESVIRIDAE; HUMAN HERPESVIRUS 5;

CELL LINE; CYTOMEGALOVIRUS; CYTOMEGALOVIRUS INFECTIONS; EPITHELIAL CELLS; FIBROBLASTS; HUMANS; MEMBRANE GLYCOPROTEINS; MUTATION; POLYETHYLENE GLYCOLS; VIRAL ENVELOPE PROTEINS; VIRAL TROPISM; VIRUS INTERNALIZATION; VIRUS REPLICATION;

EID: 84937479209     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.01325-15     Document Type: Article

References (64)

1. Britt WJ. 2008. Manifestations of human cytomegalovirus infection: proposed mechanisms of acute and chronic disease. Curr Top Microbiol Immunol 325:417-470.
2. Streblow DN, Orloff SL, Nelson JA. 2007. Acceleration of allograft failure by cytomegalovirus. Curr Opin Immunol 19:577-582. http://dx.doi.org/10.1016/j.coi.2007.07.012.
3. Boppana SB, Fowler KB, Pass RF, Rivera LB, Bradford RD, Lakeman FD, Britt WJ. 2005. Congenital cytomegalovirus infection: association between virus burden in infancy and hearing loss. J Pediatr 146:817-823. http://dx.doi.org/10.1016/j.jpeds.2005.01.059.
4. Plachter B, Sinzger C, Jahn G. 1996. Cell types involved in replication and distribution of human cytomegalovirus. Adv Virus Res 46:195-261. http://dx.doi.org/10.1016/S0065-3527(08)60073-1.
5. Sinzger C, Grefte A, Plachter B, Gouw AS, The TH, Jahn G. 1995. Fibroblasts, epithelial cells, endothelial cells and smooth muscle cells are major targets of human cytomegalovirus infection in lung and gastrointestinal tissues. J Gen Virol 76:741-750. http://dx.doi.org/10.1099/0022-1317-76-4-741.
6. Luo MH, Schwartz PH, Fortunato EA. 2008. Neonatal neural progenitor cells and their neuronal and glial cell derivatives are fully permissive for human cytomegalovirus infection. J Virol 82:9994-10007. http://dx.doi.org/10.1128/JVI.00943-08.
7. Vanarsdall AL, Johnson DC. 2012. Human cytomegalovirus entry into cells. Curr Opin Virol 2:37-42. http://dx.doi.org/10.1016/j.coviro.2012.01.001.
8. Chowdary TK, Cairns TM, Atanasiu D, Cohen GH, Eisenberg RJ, Heldwein EE. 2010. Crystal structure of the conserved herpesvirus fusion regulator complex gH-gL. Nat Struct Mol Biol 17:882-888. http://dx.doi.org/10.1038/nsmb.1837.
9. Heldwein EE, Lou H, Bender FC, Cohen GH, Eisenberg RJ, Harrison SC. 2006. Crystal structure of glycoprotein B from herpes simplex virus 1. Science 313:217-220. http://dx.doi.org/10.1126/science.1126548.
10. Backovic M, Longnecker R, Jardetzky TS. 2009. Structure of a trimeric variant of the Epstein-Barr virus glycoprotein B. Proc Natl Acad Sci U S A 106:2880-2885. http://dx.doi.org/10.1073/pnas.0810530106.
11. Matsuura H, Kirschner AN, Longnecker R, Jardetzky TS. 2010. Crystal structure of the Epstein-Barr virus (EBV) glycoprotein H/glycoprotein L (gH/gL) complex. Proc Natl Acad Sci U S A 107:22641-22646. http://dx.doi.org/10.1073/pnas.1011806108.
12. Atanasiu D, Whitbeck JC, Cairns TM, Reilly B, Cohen GH, Eisenberg RJ. 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. http://dx.doi.org/10.1073/pnas.0707452104.
13. Atanasiu D, Whitbeck JC, de Leon MP, Lou H, Hannah BP, Cohen GH, Eisenberg RJ. 2010. Bimolecular complementation defines functional regions of herpes simplex virus gB that are involved with gH/gL as a necessary step leading to cell fusion. J Virol 84:3825-3834. http://dx.doi.org/10.1128/JVI.02687-09.
14. Atanasiu D, Saw WT, Gallagher JR, Hannah BP, Matsuda Z, Whitbeck JC, Cohen GH, Eisenberg RJ. 2013. Dual split protein-based fusion assay reveals that mutations to herpes simplex virus (HSV) glycoprotein gB alter the kinetics of cell-cell fusion induced by HSV entry glycoproteins. J Virol 87:11332-11345. http://dx.doi.org/10.1128/JVI.01700-13.
15. Cairns TM, Whitbeck JC, Lou H, Heldwein EE, Chowdary TK, Eisenberg RJ, Cohen GH. 2011. Capturing the herpes simplex virus core fusion complex (gB-gH/gL) in an acidic environment. J Virol 85:6175-6184. http://dx.doi.org/10.1128/JVI.00119-11.
16. Chesnokova LS, Hutt-Fletcher LM. 2011. Fusion of Epstein-Barr virus with epithelial cells can be triggered by alphavbeta5 in addition to alphavbeta6 and alphavbeta8, and integrin binding triggers a conformational change in glycoproteins gHgL. J Virol 85:13214-13223. http://dx.doi.org/10.1128/JVI.05580-11.
17. Plate AE, Smajlovic J, Jardetzky TS, Longnecker R. 2009. Functional analysis of glycoprotein L (gL) from rhesus lymphocryptovirus in Epstein-Barr virus-mediated cell fusion indicates a direct role of gL in gB-induced membrane fusion. J Virol 83:7678-7689. http://dx.doi.org/10.1128/JVI.00457-09.
18. 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. http://dx.doi.org/10.1038/nrmicro2548.
19. Sharma S, Wisner TW, Johnson DC, Heldwein EE. 2013. HCMV gB shares structural and functional properties with gB proteins from other herpesviruses. Virology 435:239-249. http://dx.doi.org/10.1016/j.virol.2012.09.024.
20. Vanarsdall AL, Ryckman BJ, Chase MC, Johnson DC. 2008. Human cytomegalovirus glycoproteins gB and gH/gL mediate epithelial cell-cell fusion when expressed either in cis or in trans. J Virol 82:11837-11850. http://dx.doi.org/10.1128/JVI.01623-08.
21. Adler B, Scrivano L, Ruzcics Z, Rupp B, Sinzger C, Koszinowski U. 2006. Role of human cytomegalovirus UL131A in cell type-specific virus entry and release. J Gen Virol 87:2451-2460. http://dx.doi.org/10.1099/vir.0.81921-0.
22. Huber MT, Compton T. 1997. Characterization of a novel third member of the human cytomegalovirus glycoprotein H-glycoprotein L complex. J Virol 71:5391-5398.
23. Li L, Nelson JA, Britt WJ. 1997. Glycoprotein H-related complexes of human cytomegalovirus: identification of a third protein in the gCIII complex. J Virol 71:3090-3097.
24. Wang D, Shenk T. 2005. Human cytomegalovirus virion protein complex required for epithelial and endothelial cell tropism. Proc Natl Acad Sci U S A 102:18153-18158. http://dx.doi.org/10.1073/pnas.0509201102.
25. Zhou M, Yu Q, Wechsler A, Ryckman BJ. 2013. Comparative analysis of gO isoforms reveals that strains of human cytomegalovirus differ in the ratio of gH/gL/gO and gH/gL/UL128-131 in the virion envelope. J Virol 87:9680-9690. http://dx.doi.org/10.1128/JVI.01167-13.
26. Ciferri C, Chandramouli S, Donnarumma D, Nikitin PA, Cianfrocco MA, Gerrein R, Feire AL, Barnett SW, Lilja AE, Rappuoli R, Norais N, Settembre EC, Carfi A. 2015. Structural and biochemical studies of HCMVgH/gL/gO and pentamer reveal mutually exclusive cell entry complexes. Proc Natl Acad Sci U S A 112:1767-1772. http://dx.doi.org/10.1073/pnas.1424818112.
27. Ryckman BJ, Jarvis MA, Drummond DD, Nelson JA, Johnson DC. 2006. Human cytomegalovirus entry into epithelial and endothelial cells depends on genes UL128 to UL150 and occurs by endocytosis and low-pH fusion. J Virol 80:710-722. http://dx.doi.org/10.1128/JVI.80.2.710-722.2006.
28. Hahn G, Revello MG, Patrone M, Percivalle E, Campanini G, Sarasini A, Wagner M, Gallina A, Milanesi G, Koszinowski U, Baldanti F, Gerna G. 2004. Human cytomegalovirus UL131-128 genes are indispensable for virus growth in endothelial cells and virus transfer to leukocytes. J Virol 78:10023-10033. http://dx.doi.org/10.1128/JVI.78.18.10023-10033.2004.
29. Wang D, Shenk T. 2005. Human cytomegalovirus UL131 open reading frame is required for epithelial cell tropism. J Virol 79:10330-10338. http://dx.doi.org/10.1128/JVI.79.16.10330-10338.2005.
30. Straschewski S, Patrone M, Walther P, Gallina A, Mertens T, Frascaroli G. 2011. Protein pUL128 of human cytomegalovirus is necessary for monocyte infection and blocking of migration. J Virol 85:5150-5158. http://dx.doi.org/10.1128/JVI.02100-10.
31. Hobom U, Brune W, Messerle M, Hahn G, Koszinowski UH. 2000. Fast screening procedures for random transposon libraries of cloned herpesvirus genomes: mutational analysis of human cytomegalovirus envelope glycoprotein genes. J Virol 74:7720-7729. http://dx.doi.org/10.1128/JVI.74.17.7720-7729.2000.
32. Dunn W, Chou C, Li H, Hai R, Patterson D, Stolc V, Zhu H, Liu F. 2003. Functional profiling of a human cytomegalovirus genome. Proc Natl Acad Sci U S A 100:14223-14228. http://dx.doi.org/10.1073/pnas.2334032100.
33. Jiang XJ, Adler B, Sampaio KL, Digel M, Jahn G, Ettischer N, Stierhof YD, Scrivano L, Koszinowski U, Mach M, Sinzger C. 2008. UL74 of human cytomegalovirus contributes to virus release by promoting secondary envelopment of virions. J Virol 82:2802-2812. http://dx.doi.org/10.1128/JVI.01550-07.
34. Wille PT, Knoche AJ, Nelson JA, Jarvis MA, Johnson DC. 2010. A human cytomegalovirus gO-null mutant fails to incorporate gH/gL into the virion envelope and is unable to enter fibroblasts and epithelial and endothelial cells. J Virol 84:2585-2596. http://dx.doi.org/10.1128/JVI.02249-09.
35. Stanton RJ, Baluchova K, Dargan DJ, Cunningham C, Sheehy O, Seirafian S, McSharry BP, Neale ML, Davies JA, Tomasec P, Davison AJ, Wilkinson GW. 2010. Reconstruction of the complete human cytomegalovirus genome in a BAC reveals RL13 to be a potent inhibitor of replication. J Clin Invest 120:3191-3208. http://dx.doi.org/10.1172/JCI42955.
36. Murphy E, Yu D, Grimwood J, Schmutz J, Dickson M, Jarvis MA, Hahn G, Nelson JA, Myers RM, Shenk TE. 2003. Coding potential of laboratory and clinical strains of human cytomegalovirus. Proc Natl Acad Sci U S A 100:14976-14981. http://dx.doi.org/10.1073/pnas.2136652100.
37. Sinzger C, Hahn G, Digel M, Katona R, Sampaio KL, Messerle M, Hengel H, Koszinowski U, Brune W, Adler B. 2008. Cloning and sequencing of a highly productive, endotheliotropic virus strain derived from human cytomegalovirus TB40/E. J Gen Virol 89:359-368. http://dx.doi.org/10.1099/vir.0.83286-0.
38. Schoppel K, Hassfurther E, Britt W, Ohlin M, Borrebaeck CA, Mach M. 1996. Antibodies specific for the antigenic domain 1 of glycoprotein B (gpUL55) of human cytomegalovirus bind to different substructures. Virology 216:133-145. http://dx.doi.org/10.1006/viro.1996.0040.
39. Chee M, Rudolph SA, Plachter B, Barrell B, Jahn G. 1989. Identification of the major capsid protein gene of human cytomegalovirus. J Virol 63: 1345-1353.
40. Ryckman BJ, Rainish BL, Chase MC, Borton JA, Nelson JA, Jarvis MA, Johnson DC. 2008. Characterization of the human cytomegalovirus gH/ gL/UL128-131 complex that mediates entry into epithelial and endothelial cells. J Virol 82:60-70. http://dx.doi.org/10.1128/JVI.01910-07.
41. Bughio F, Elliott DA, Goodrum F. 2013. An endothelial cell-specific requirement for the UL133-UL138 locus of human cytomegalovirus for efficient virus maturation. J Virol 87:3062-3075. http://dx.doi.org/10.1128/JVI.02510-12.
42. Umashankar M, Petrucelli A, Cicchini L, Caposio P, Kreklywich CN, Rak M, Bughio F, Goldman DC, Hamlin KL, Nelson JA, Fleming WH, Streblow DN, Goodrum F. 2011. A novel human cytomegalovirus locus modulates cell type-specific outcomes of infection. PLoS Pathog 7:e1002444. http://dx.doi.org/10.1371/journal.ppat.1002444.
43. Saccoccio FM, Sauer AL, Cui X, Armstrong AE, Habib E-SE, Johnson DC, Ryckman BJ, Klingelhutz AJ, Adler SP, McVoy MA. 2011. Peptides from cytomegalovirus UL130 and UL131 proteins induce high titer antibodies that block viral entry into mucosal epithelial cells. Vaccine 29: 2705-2711. http://dx.doi.org/10.1016/j.vaccine.2011.01.079.
44. Kuhn CW, Bancroft JB. 1961. Concentration and specific infectivity changes of alfalfa mosaic virus during systemic infection. Virology 15: 281-288. http://dx.doi.org/10.1016/0042-6822(61)90359-2.
45. Bachrach HL, Schwerdt CE. 1954. Purification studies on Lansing poliomyelitis virus. II. Analytical electron microscopic identification of the infectious particle in preparations of high specific infectivity. J Immunol 72:30-38.
46. Bang FB. 1948. Studies on Newcastle disease virus; characters of the virus itself with particular reference to electron microscopy. J Exp Med 88:251-266. http://dx.doi.org/10.1084/jem.88.2.251.
47. Thomas JA, Ott DE, Gorelick RJ. 2007. Efficiency of human immunodeficiency virus type 1 postentry infection processes: evidence against disproportionate numbers of defective virions. J Virol 81:4367-4370. http://dx.doi.org/10.1128/JVI.02357-06.
48. Scrivano L, Sinzger C, Nitschko H, Koszinowski UH, Adler B. 2011. HCMV spread and cell tropism are determined by distinct virus populations. PLoS Pathog 7:e1001256. http://dx.doi.org/10.1371/journal.ppat.1001256.
49. Li L, Coelingh KL, Britt WJ. 1995. Human cytomegalovirus neutralizing antibody-resistant phenotype is associated with reduced expression of glycoprotein H. J Virol 69:6047-6053.
50. Benyesh-Melnick M, Probstmeyer F, McCombs R, Brunschwig JP, Vonka V. 1966. Correlation between infectivity and physical virus particles in human cytomegalovirus. J Bacteriol 92:1555-1561.
51. Smith KO, Rasmussen L. 1963. Morphology of cytomegalovirus (salivary gland virus). J Bacteriol 85:1319-1325.
52. Stinski MF, Mocarski ES, Thomsen DR. 1979. DNA of human cytomegalovirus: size heterogeneity and defectiveness resulting from serial undiluted passage. J Virol 31:231-239.
53. Irmiere A, Gibson W. 1983. Isolation and characterization of a noninfectious virion-like particle released from cells infected with human strains of cytomegalovirus. Virology 130:118-133. http://dx.doi.org/10.1016/0042-6822(83)90122-8.
54. Varnum SM, Streblow DN, Monroe ME, Smith P, Auberry KJ, Pasa-Tolic L, Wang D, Camp DG, Rodland K, Wiley S, Britt W, Shenk T, Smith RD, Nelson JA. 2004. Identification of proteins in human cytomegalovirus (HCMV) particles: the HCMV proteome. J Virol 78:10960-10966. http://dx.doi.org/10.1128/JVI.78.20.10960-10966.2004.
55. Ahlqvist J, Mocarski E. 2011. Cytomegalovirus UL103 controls virion and dense body egress. J Virol 85:5125-5135. http://dx.doi.org/10.1128/JVI.01682-10.
56. Heider JA, Bresnahan WA, Shenk TE. 2002. Construction of a rationally designed human cytomegalovirus variant encoding a temperaturesensitive immediate-early 2 protein. Proc Natl Acad Sci U S A 99:3141-3146. http://dx.doi.org/10.1073/pnas.052710599.
57. Haspot F, Lavault A, Sinzger C, Laib Sampaio K, Stierhof YD, Pilet P, Bressolette-Bodin C, Halary F. 2012. Human cytomegalovirus entry into dendritic cells occurs via a macropinocytosis-like pathway in a pHindependent and cholesterol-dependent manner. PLoS One 7:e34795. http://dx.doi.org/10.1371/journal.pone.0034795.
58. Vanarsdall AL, Wisner TW, Lei H, Kazlauskas A, Johnson DC. 2012. PDGF receptor-alpha does not promote HCMV entry into epithelial and endothelial cells but increased quantities stimulate entry by an abnormal pathway. PLoS Pathog 8:e1002905. http://dx.doi.org/10.1371/journal.ppat.1002905.
59. Murrell I, Tomasec P, Wilkie GS, Dargan DJ, Davison AJ, Stanton RJ. 2013. Impact of sequence variation in the UL128 locus on production of human cytomegalovirus in fibroblast and epithelial cells. J Virol 87: 10489-10500. http://dx.doi.org/10.1128/JVI.01546-13.
60. Nogalski MT, Chan GC, Stevenson EV, Collins-McMillen DK, Yurochko AD. 2013. The HCMV gH/gL/UL128-131 complex triggers the specific cellular activation required for efficient viral internalization into target monocytes. PLoS Pathog 9:e1003463. http://dx.doi.org/10.1371/journal.ppat.1003463.
61. Lemmermann NA, Krmpotic A, Podlech J, Brizic I, Prager A, Adler H, Karbach A, Wu Y, Jonjic S, Reddehase MJ, Adler B. 2015. Nonredundant and redundant roles of cytomegalovirus gH/gL complexes in host organ entry and intra-tissue spread. PLoS Pathog 11:e1004640. http://dx.doi.org/10.1371/journal.ppat.1004640.
62. Wussow F, Yue Y, Martinez J, Deere JD, Longmate J, Herrmann A, Barry PA, Diamond DJ. 2013. A vaccine based on the rhesus cytomegalovirus UL128 complex induces broadly neutralizing antibodies in rhesus macaques. J Virol 87:1322-1332. http://dx.doi.org/10.1128/JVI.01669-12.
63. Kabanova A, Perez L, Lilleri D, Marcandalli J, Agatic G, Becattini S, Preite S, Fuschillo D, Percivalle E, Sallusto F, Gerna G, Corti D, Lanzavecchia A. 2014. Antibody-driven design of a human cytomegalovirus gHgLpUL128L subunit vaccine that selectively elicits potent neutralizing antibodies. Proc Natl Acad SciUSA111:17965-17970. http://dx.doi.org/10.1073/pnas.1415310111.
64. Wen Y, Monroe J, Linton C, Archer J, Beard CW, Barnett SW, Palladino G, Mason PW, Carfi A, Lilja AE. 2014. Human cytomegalovirus gH/gL/UL128/UL130/UL131A complex elicits potently neutralizing antibodies in mice. Vaccine 32:3796-3804. http://dx.doi.org/10.1016/j.vaccine.2014.05.004.