Skip to main content

Structure and Function of Respiratory Syncytial Virus Surface Glycoproteins

  • Chapter
  • First Online:
Challenges and Opportunities for Respiratory Syncytial Virus Vaccines

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 372))

Abstract

The two major glycoproteins on the surface of the respiratory syncytial virus (RSV) virion, the attachment glycoprotein (G) and the fusion glycoprotein (F), control the initial phases of infection. G targets the ciliated cells of the airways, and F causes the virion membrane to fuse with the target cell membrane. The F protein is the major target for antiviral drug development, and both G and F glycoproteins are the antigens targeted by neutralizing antibodies induced by infection. In this chapter, we review the structure and function of the RSV surface glycoproteins, including recent X-ray crystallographic data of the F glycoprotein in its pre- and postfusion conformations, and discuss how this information informs antigen selection and vaccine development.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Anderson LJ, Bingham P, Hierholzer JC (1988) Neutralization of respiratory syncytial virus by individual and mixtures of F and G protein monoclonal antibodies. J Virol 62(11):4232–4238

    CAS  PubMed Central  PubMed  Google Scholar 

  • Arumugham RG, Seid RC, Doyle S, Hildreth SW, Paradiso PR (1989) Fatty acid acylation of the fusion glycoprotein of human respiratory syncytial virus. J Biol Chem 264(18):10339–10342

    CAS  PubMed  Google Scholar 

  • Barr FE, Pedigo H, Johnson TR, Shepherd VL (2000) Surfactant protein-A enhances uptake of respiratory syncytial virus by monocytes and U937 macrophages. Am J Respir Cell Mol Biol 23(5):586–592

    Article  CAS  PubMed  Google Scholar 

  • Behera AK, Matsuse H, Kumar M, Kong X, Lockey RF, Mohapatra SS (2001) Blocking intercellular adhesion molecule-1 on human epithelial cells decreases respiratory syncytial virus infection. Biochem Biophys Res Commun 280(1):188–195

    Article  CAS  PubMed  Google Scholar 

  • Bolt G, Pedersen LØ, Birkeslund HH (2000) Cleavage of the respiratory syncytial virus fusion protein is required for its surface expression: role of furin. Virus Res 68(1):25–33

    Article  CAS  PubMed  Google Scholar 

  • Bonfanti J-F, Meyer C, Doublet F, Fortin J, Muller P, Queguiner L, Gevers T, Janssens P, Szel H, Willebrords R, Timmerman P, Wuyts K, van Remoortere P, Janssens F, Wigerinck P, Andries K (2008) Selection of a respiratory syncytial virus fusion inhibitor clinical candidate. 2. Discovery of a morpholinopropylaminobenzimidazole derivative (TMC353121). J Med Chem 51(4):875–896

    Article  CAS  PubMed  Google Scholar 

  • Bukreyev A, Whitehead SS, Murphy BR, Collins PL (1997) Recombinant respiratory syncytial virus from which the entire SH gene has been deleted grows efficiently in cell culture and exhibits site-specific attenuation in the respiratory tract of the mouse. J Virol 71(12):8973–8982

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bukreyev A, Yang L, Collins PL (2012) The secreted G protein of human respiratory syncytial virus antagonizes antibody-mediated restriction of replication involving macrophages and complement. J Virol 86(19):10880–10884

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bukreyev A, Yang L, Fricke J, Cheng L, Ward JM, Murphy BR, Collins PL (2008) The secreted form of respiratory syncytial virus G glycoprotein helps the virus evade antibody-mediated restriction of replication by acting as an antigen decoy and through effects on Fc receptor-bearing leukocytes. J Virol 82(24):12191–12204

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Calder LJ, Gonzalez-Reyes L, Garcia-Barreno B, Wharton SA, Skehel JJ, Wiley DC, Melero JA (2000) Electron microscopy of the human respiratory syncytial virus fusion protein and complexes that it forms with monoclonal antibodies. Virology 271(1):122–131

    Article  CAS  PubMed  Google Scholar 

  • Carter SD, Dent KC, Atkins E, Foster TL, Verow M, Gorny P, Harris M, Hiscox JA, Ranson NA, Griffin S, Barr JN (2010) Direct visualization of the small hydrophobic protein of human respiratory syncytial virus reveals the structural basis for membrane permeability. FEBS Lett 584(13):2786–2790

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chaiwatpongsakorn S, Epand RF, Collins PL, Epand RM, Peeples ME (2011) Soluble respiratory syncytial virus fusion protein in the fully cleaved, pretriggered state is triggered by exposure to low-molarity buffer. J Virol 85(8):3968–3977

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Choi Y, Mason CS, Jones LP, Crabtree J, Jorquera PA, Tripp RA (2012) Antibodies to the central conserved region of respiratory syncytial virus (RSV) G protein block RSV G protein CX3C-CX3CR1 binding and cross-neutralize RSV A and B strains. Viral Immunol 25(3):193–203

    CAS  PubMed  Google Scholar 

  • Cianci C, Langley DR, Dischino DD, Sun Y, Yu K-L, Stanley A, Roach J, Li Z, Dalterio R, Colonno R, Meanwell NA, Krystal M (2004a) Targeting a binding pocket within the trimer-of-hairpins: Small-molecule inhibition of viral fusion. Proc Natl Acad Sci USA 101(42):15046–15051

    Article  CAS  PubMed  Google Scholar 

  • Cianci C, Yu KL, Combrink K, Sin N, Pearce B, Wang A, Civiello R, Voss S, Luo G, Kadow K, Genovesi EV, Venables B, Gulgeze H, Trehan A, James J, Lamb L, Medina I, Roach J, Yang Z, Zadjura L, Colonno R, Clark J, Meanwell N, Krystal M (2004b) Orally active fusion inhibitor of respiratory syncytial virus. Antimicrob Agents Chemother 48(2):413–422

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Collins PL, Huang YT, Wertz GW (1984) Nucleotide sequence of the gene encoding the fusion (F) glycoprotein of human respiratory syncytial virus. Proc Natl Acad Sci USA 81(24):7683–7687

    Article  CAS  PubMed  Google Scholar 

  • Collins PL, Mottet G (1991) Post-translational processing and oligomerization of the fusion glycoprotein of human respiratory syncytial virus. J Gen Virol 72(12):3095–3101

    Article  CAS  PubMed  Google Scholar 

  • Collins PL, Mottet G (1992) Oligomerization and post-translational processing of glycoprotein G of human respiratory syncytial virus: altered O-glycosylation in the presence of brefeldin A. J Gen Virol 73(4):849–863

    Article  CAS  PubMed  Google Scholar 

  • Collins PL, Mottet G (1993) Membrane orientation and oligomerization of the small hydrophobic protein of human respiratory syncytial virus. J Gen Virol 74(7):1445–1450

    Article  CAS  PubMed  Google Scholar 

  • Connolly SA, Leser GP, Yin HS, Jardetzky TS, Lamb RA (2006) Refolding of a paramyxovirus F protein from prefusion to postfusion conformations observed by liposome binding and electron microscopy. Proc Natl Acad Sci USA 103(47):17903–17908

    Article  CAS  PubMed  Google Scholar 

  • Costello HM, Ray WC, Chaiwatpongsakorn S, Peeples ME (2012) Targeting RSV with vaccines and small molecule drugs. Infect Disord Drug Targets 12(2):110–128

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Day ND, Branigan PJ, Liu C, Gutshall LL, Luo J, Melero JA, Sarisky RT, Del Vecchio AM (2006) Contribution of cysteine residues in the extracellular domain of the F protein of human respiratory syncytial virus to its function. Virol J 3:34

    Article  PubMed Central  PubMed  Google Scholar 

  • Douglas JL, Panis ML, Ho E, Lin KY, Krawczyk SH, Grant DM, Cai R, Swaminathan S, Cihlar T (2003) Inhibition of respiratory syncytial virus fusion by the small molecule VP-14637 via specific interactions with F protein. J Virol 77(9):5054–5064

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Escribano-Romero E, Rawling J, Garcia-Barreno B, Melero JA (2004) The soluble form of human respiratory syncytial virus attachment protein differs from the membrane-bound form in its oligomeric state but is still capable of binding to cell surface proteoglycans. J Virol 78(7):3524–3532

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Eshaghi A, Duvvuri VR, Lai R, Nadarajah JT, Li A, Patel SN, Low DE, Gubbay JB (2012) Genetic variability of human respiratory syncytial virus A strains circulating in Ontario: a novel genotype with a 72 nucleotide G gene duplication. PLoS ONE 7(3):e32807

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Feldman SA, Audet S, Beeler JA (2000) The fusion glycoprotein of human respiratory syncytial virus facilitates virus attachment and infectivity via an interaction with cellular heparan sulfate. J Virol 74(14):6442–6447

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Feldman SA, Hendry RM, Beeler JA (1999) Identification of a linear heparin binding domain for human respiratory syncytial virus attachment glycoprotein G. J Virol 73(8):6610–6617

    CAS  PubMed Central  PubMed  Google Scholar 

  • Frank S, Kammerer RA, Mechling D, Schulthess T, Landwehr R, Bann J, Guo Y, Lustig A, Bachinger HP, Engel J (2001) Stabilization of short collagen-like triple helices by protein engineering. J Mol Biol 308(5):1081–1089

    Article  CAS  PubMed  Google Scholar 

  • Fuentes S, Tran KC, Luthra P, Teng MN, He B (2007) Function of the respiratory syncytial virus small hydrophobic protein. J Virol 81(15):8361–8366

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gan S-W, Tan E, Lin X, Yu D, Wang J, Tan GM-Y, Vararattanavech A, Yeo CY, Soon CH, Soong TW, Pervushin K, Torres J (2012) The small hydrophobic protein of the human respiratory syncytial virus forms pentameric ion channels. J Biol Chem 287(29):24671–24689

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Beato R, Martinez I, Franci C, Real FX, Garcia-Barreno B, Melero JA (1996) Host cell effect upon glycosylation and antigenicity of human respiratory syncytial virus G glycoprotein. Virology 221(2):301–309

    Article  CAS  PubMed  Google Scholar 

  • Gonzalez-Reyes L, Ruiz-Arguello MB, Garcia-Barreno B, Calder L, Lopez JA, Albar JP, Skehel JJ, Wiley DC, Melero JA (2001) Cleavage of the human respiratory syncytial virus fusion protein at two distinct sites is required for activation of membrane fusion. Proc Natl Acad Sci USA 98(17):9859–9864

    Article  CAS  PubMed  Google Scholar 

  • Gorman JJ, Ferguson BL, Speelman D, Mills J (1997) Determination of the disulfide bond arrangement of human respiratory syncytial virus attachment (G) protein by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Protein Sci 6(6):1308–1315

    Article  CAS  PubMed  Google Scholar 

  • Gruber C, Levine S (1983) Respiratory syncytial virus polypeptides. III. The envelope-associated proteins. J Gen Virol 64(4):825–832

    Article  CAS  PubMed  Google Scholar 

  • Gupta N, Manevich Y, Kazi AS, Tao JQ, Fisher AB, Bates SR (2006) Identification and characterization of p63 (CKAP4/ERGIC-63/CLIMP-63), a surfactant protein A binding protein, on type II pneumocytes. Am J Physiol Lung Cell Mol Physiol 291(3):L436–L446

    Article  CAS  PubMed  Google Scholar 

  • Hallak LK, Collins PL, Knudson W, Peeples ME (2000a) Iduronic acid-containing glycosaminoglycans on target cells are required for efficient respiratory syncytial virus infection. Virology 271(2):264–275

    Article  CAS  PubMed  Google Scholar 

  • Hallak LK, Kwilas SA, Peeples ME (2007) Interaction between respiratory syncytial virus and glycosaminoglycans, including heparan sulfate. Methods Mol Biol 379:15–34

    Article  CAS  PubMed  Google Scholar 

  • Hallak LK, Spillmann D, Collins PL, Peeples ME (2000b) Glycosaminoglycan sulfation requirements for respiratory syncytial virus infection. J Virol 74(22):10508–10513

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Haynes LM, Caidi H, Radu GU, Miao C, Harcourt JL, Tripp RA, Anderson LJ (2009) Therapeutic monoclonal antibody treatment targeting respiratory syncytial virus (RSV) G protein mediates viral clearance and reduces the pathogenesis of RSV infection in BALB/c mice. J Infect Dis 200(3):439–447

    Article  CAS  PubMed  Google Scholar 

  • Haynes LM, Moore DD, Kurt-Jones EA, Finberg RW, Anderson LJ, Tripp RA (2001) Involvement of toll-like receptor 4 in innate immunity to respiratory syncytial virus. J Virol 75(22):10730–10737

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hendricks DA, Baradaran K, McIntosh K, Patterson JL (1987) Appearance of a soluble form of the G protein of respiratory syncytial virus in fluids of infected cells. J Gen Virol 68(6):1705–1714

    Article  CAS  PubMed  Google Scholar 

  • Hendricks DA, McIntosh K, Patterson JL (1988) Further characterization of the soluble form of the G glycoprotein of respiratory syncytial virus. J Virol 62(7):2228–2233

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hickling TP, Malhotra R, Bright H, McDowell W, Blair ED, Sim RB (2000) Lung surfactant protein A provides a route of entry for respiratory syncytial virus into host cells. Viral Immunol 13(1):125–135

    Article  CAS  PubMed  Google Scholar 

  • Huang K, Incognito L, Cheng X, Ulbrandt ND, Wu H (2010) Respiratory syncytial virus-neutralizing monoclonal antibodies motavizumab and palivizumab inhibit fusion. J Virol 84(16):8132–8140

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Johnson S, Oliver C, Prince GA, Hemming VG, Pfarr DS, Wang SC, Dormitzer M, O’Grady J, Koenig S, Tamura JK, Woods R, Bansal G, Couchenour D, Tsao E, Hall WC, Young JF (1997) Development of a humanized monoclonal antibody (MEDI-493) with potent in vitro and in vivo activity against respiratory syncytial virus. J Infect Dis 176(5):1215–1224

    Article  CAS  PubMed  Google Scholar 

  • Johnson TR, McLellan JS, Graham BS (2012) Respiratory syncytial virus glycoprotein G interacts with DC-SIGN and L-SIGN to activate ERK1 and ERK2. J Virol 86(3):1339–1347

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Karron RA, Buonagurio DA, Georgiu AF, Whitehead SS, Adamus JE, Clements-Mann ML, Harris DO, Randolph VB, Udem SA, Murphy BR, Sidhu MS (1997) Respiratory syncytial virus (RSV) SH and G proteins are not essential for viral replication in vitro: clinical evaluation and molecular characterization of a cold-passaged, attenuated RSV subgroup B mutant. Proc Natl Acad Sci USA 94(25):13961–13966

    Article  CAS  PubMed  Google Scholar 

  • Kim S, Joo DH, Lee JB, Shim BS, Cheon IS, Jang JE, Song HH, Kim KH, Song MK, Chang J (2012) Dual role of respiratory syncytial virus glycoprotein fragment as a mucosal immunogen and chemotactic adjuvant. PLoS ONE 7(2):e32226

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kong X, San Juan H, Behera A, Peeples ME, Wu J, Lockey RF, Mohapatra SS (2004) ERK-1/2 activity is required for efficient RSV infection. FEBS Lett 559(1–3):33–38

    Article  CAS  PubMed  Google Scholar 

  • Krusat T, Streckert HJ (1997) Heparin-dependent attachment of respiratory syncytial virus (RSV) to host cells. Arch Virol 142(6):1247–1254

    Article  CAS  PubMed  Google Scholar 

  • Kwakkenbos MJ, Diehl SA, Yasuda E, Bakker AQ, van Geelen CMM, Lukens MV, van Bleek GM, Widjojoatmodjo MN, Bogers WMJM, Mei H, Radbruch A, Scheeren FA, Spits H, Beaumont T (2010) Generation of stable monoclonal antibody-producing B cell receptor-positive human memory B cells by genetic programming. Nat Med 16(1):123–128

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kwilas S, Liesman RM, Zhang L, Walsh E, Pickles RJ, Peeples ME (2009) Respiratory syncytial virus grown in Vero cells contains a truncated attachment protein that alters its infectivity and dependence on glycosaminoglycans. J Virol 83(20):10710–10718

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lambert DM, Barney S, Lambert AL, Guthrie K, Medinas R, Davis DE, Bucy T, Erickson J, Merutka G, Petteway SR (1996) Peptides from conserved regions of paramyxovirus fusion (F) proteins are potent inhibitors of viral fusion. Proc Natl Acad Sci USA 93(5):2186–2191

    Article  CAS  PubMed  Google Scholar 

  • Levine S (1977) Polypeptides of respiratory syncytial virus. J Virol 21(1):427–431

    CAS  PubMed Central  PubMed  Google Scholar 

  • Levine S, Klaiber-Franco R, Paradiso PR (1987) Demonstration that glycoprotein G is the attachment protein of respiratory syncytial virus. J Gen Virol 68(Pt 9):2521–2524

    Article  CAS  PubMed  Google Scholar 

  • Li P, Mc LRHW, Brown G, Sugrue RJ (2007) Functional analysis of the N-linked glycans within the fusion protein of respiratory syncytial virus. Methods Mol Biol 379:69–83

    Article  CAS  PubMed  Google Scholar 

  • Libon C, Desplanches F, Corbiere JC, Haeuw JF, Robert A, Nguyen T (2007) Identification of the component responsible for the type III hypersensitivity reaction (HS III) induced by BBG2Na, a subunit respiratory syncytial virus (RSV) vaccine. Paper presented at the 6th international respiratory syncytial virus symposium, Marco Island, Florida, 25–28 October 2007

    Google Scholar 

  • Magro M, Andreu D, Gomez-Puertas P, Melero JA, Palomo C (2010) Neutralization of human respiratory syncytial virus infectivity by antibodies and low-molecular-weight compounds targeted against the fusion glycoprotein. J Virol 84(16):7970–7982

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Magro M, Mas V, Chappell K, Vazquez M, Cano O, Luque D, Terron MC, Melero JA, Palomo C (2012) Neutralizing antibodies against the preactive form of respiratory syncytial virus fusion protein offer unique possibilities for clinical intervention. Proc Natl Acad Sci USA 109(8):3089–3094

    Article  CAS  PubMed  Google Scholar 

  • Malhotra R, Ward M, Bright H, Priest R, Foster MR, Hurle M, Blair E, Bird M (2003) Isolation and characterisation of potential respiratory syncytial virus receptor(s) on epithelial cells. Microbes Infect 5(2):123–133

    Article  CAS  PubMed  Google Scholar 

  • McLellan JS, Chen M, Chang J-S, Yang Y, Kim A, Graham BS, Kwong PD (2010a) Structure of a major antigenic site on the respiratory syncytial virus fusion glycoprotein in complex with neutralizing antibody 101F. J Virol 84(23):12236–12244

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • McLellan JS, Chen M, Kim A, Yang Y, Graham BS, Kwong PD (2010b) Structural basis of respiratory syncytial virus neutralization by motavizumab. Nat Struct Mol Biol 17(2):248–250

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • McLellan JS, Chen M, Leung S, Graepel KW, Du X, Yang Y, Zhou T, Baxa U, Yasuda E, Beaumont T, Kumar A, Modjarrad K, Zheng Z, Zhao M, Xia N, Kwong PD, Graham BS (2013) Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody. Science 340(6136):1113–7

    Google Scholar 

  • McLellan JS, Yang Y, Graham BS, Kwong PD (2011) Structure of respiratory syncytial virus fusion glycoprotein in the postfusion conformation reveals preservation of neutralizing epitopes. J Virol 85(15):7788–7796

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Munoz FM, Piedra PA, Glezen WP (2003) Safety and immunogenicity of respiratory syncytial virus purified fusion protein-2 vaccine in pregnant women. Vaccine 21(24):3465–3467

    Article  CAS  PubMed  Google Scholar 

  • Nguyen TN, Power UF, Robert A, Haeuw JF, Helffer K, Perez A, Asin MA, Corvaia N, Libon C (2012) The respiratory syncytial virus G protein conserved domain induces a persistent and protective antibody response in rodents. PLoS ONE 7(3):e34331

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nieva JL, Madan V, Carrasco L (2012) Viroporins: structure and biological functions. Nat Rev Micro 10(8):563–574

    Article  CAS  Google Scholar 

  • Olmsted RA, Collins PL (1989) The 1A protein of respiratory syncytial virus is an integral membrane protein present as multiple, structurally distinct species. J Virol 63(5):2019–2029

    CAS  PubMed Central  PubMed  Google Scholar 

  • Plotnicky-Gilquin H, Huss T, Aubry JP, Haeuw JF, Beck A, Bonnefoy JY, Nguyen TN, Power UF (1999) Absence of lung immunopathology following respiratory syncytial virus (RSV) challenge in mice immunized with a recombinant RSV G protein fragment. Virology 258(1):128–140

    Article  CAS  PubMed  Google Scholar 

  • Power UF, Plotnicky-Gilquin H, Huss T, Robert A, Trudel M, Stahl S, Uhlen M, Nguyen TN, Binz H (1997) Induction of protective immunity in rodents by vaccination with a prokaryotically expressed recombinant fusion protein containing a respiratory syncytial virus G protein fragment. Virology 230(2):155–166

    Article  CAS  PubMed  Google Scholar 

  • Radu GU, Caidi H, Miao C, Tripp RA, Anderson LJ, Haynes LM (2010) Prophylactic treatment with a G glycoprotein monoclonal antibody reduces pulmonary inflammation in respiratory syncytial virus (RSV)-challenged naive and formalin-inactivated RSV-immunized BALB/c mice. J Virol 84(18):9632–9636

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rixon HWML, Brown G, Aitken J, McDonald T, Graham S, Sugrue RJ (2004) The small hydrophobic (SH) protein accumulates within lipid-raft structures of the Golgi complex during respiratory syncytial virus infection. J Gen Virol 85(5):1153–1165

    Article  CAS  PubMed  Google Scholar 

  • Roberts SR, Lichtenstein D, Ball LA, Wertz GW (1994) The membrane-associated and secreted forms of the respiratory syncytial virus attachment glycoprotein G are synthesized from alternative initiation codons. J Virol 68(7):4538–4546

    CAS  PubMed Central  PubMed  Google Scholar 

  • Roymans D, De Bondt HL, Arnoult E, Geluykens P, Gevers T, Van Ginderen M, Verheyen N, Kim H, Willebrords R, Bonfanti JF, Bruinzeel W, Cummings MD, van Vlijmen H, Andries K (2010) Binding of a potent small-molecule inhibitor of six-helix bundle formation requires interactions with both heptad-repeats of the RSV fusion protein. Proc Natl Acad Sci USA 107(1):308–313

    Article  CAS  PubMed  Google Scholar 

  • Ruiz-Arguello MB, Gonzalez-Reyes L, Calder LJ, Palomo C, Martin D, Saiz MJ, Garcia-Barreno B, Skehel JJ, Melero JA (2002) Effect of proteolytic processing at two distinct sites on shape and aggregation of an anchorless fusion protein of human respiratory syncytial virus and fate of the intervening segment. Virology 298(2):317–326

    Google Scholar 

  • Ruiz-Arguello MB, Martin D, Wharton SA, Calder LJ, Martin SR, Cano O, Calero M, Garcia-Barreno B, Skehel JJ, Melero JA (2004) Thermostability of the human respiratory syncytial virus fusion protein before and after activation: implications for the membrane-fusion mechanism. J Gen Virol 85(12):3677–3687

    Article  PubMed  Google Scholar 

  • Satake M, Coligan JE, Elango N, Norrby E, Venkatesan S (1985) Respiratory syncytial virus envelope glycoprotein (G) has a novel structure. Nucleic Acids Res 13(21):7795–7812

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Schepens B, De Baets S, Sedyen K, Bogaert P, Gilbert B, Piedra PA, Fiers W, Saelens X (2012) SHe’s a novel target for RSV vaccination. Paper presented at the 8th respiratory syncytial virus symposium, Santa Fe, USA, 28 September 2012

    Google Scholar 

  • Schlender J, Zimmer G, Herrler G, Conzelmann KK (2003) Respiratory syncytial virus (RSV) fusion protein subunit F2, not attachment protein G, determines the specificity of RSV infection. J Virol 77(8):4609–4616

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Stott EJ, Ball LA, Young KK, Furze J, Wertz GW (1986) Human respiratory syncytial virus glycoprotein G expressed from a recombinant vaccinia virus vector protects mice against live-virus challenge. J Virol 60(2):607–613

    CAS  PubMed Central  PubMed  Google Scholar 

  • Swanson KA, Settembre EC, Shaw CA, Dey AK, Rappuoli R, Mandl CW, Dormitzer PR, Carfi A (2011) Structural basis for immunization with postfusion respiratory syncytial virus fusion F glycoprotein (RSV F) to elicit high neutralizing antibody titers. Proc Natl Acad Sci USA 108(23):9619–9624

    Article  CAS  PubMed  Google Scholar 

  • Takimoto T, Hurwitz JL, Coleclough C, Prouser C, Krishnamurthy S, Zhan X, Boyd K, Scroggs RA, Brown B, Nagai Y, Portner A, Slobod KS (2004) Recombinant Sendai virus expressing the G glycoprotein of respiratory syncytial virus (RSV) elicits immune protection against RSV. J Virol 78(11):6043–6047

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tayyari F, Marchant D, Moraes TJ, Duan W, Mastrangelo P, Hegele RG (2011) Identification of nucleolin as a cellular receptor for human respiratory syncytial virus. Nat Med 17(9):1132–1135

    Article  CAS  PubMed  Google Scholar 

  • Techaarpornkul S, Barretto N, Peeples ME (2001) Functional analysis of recombinant respiratory syncytial virus deletion mutants lacking the small hydrophobic and/or attachment glycoprotein gene. J Virol 75(15):6825–6834

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Teng MN, Whitehead SS, Collins PL (2001) Contribution of the respiratory syncytial virus G glycoprotein and its secreted and membrane-bound forms to virus replication in vitro and in vivo. Virology 289(2):283–296

    Article  CAS  PubMed  Google Scholar 

  • Ternette N, Stefanou D, Kuate S, Uberla K, Grunwald T (2007) Expression of RNA virus proteins by RNA polymerase II dependent expression plasmids is hindered at multiple steps. Virol J 4:51

    Article  PubMed Central  PubMed  Google Scholar 

  • The IMpact-RSV Study Group (1998) Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics 102(3):531–537

    Article  Google Scholar 

  • Trento A, Galiano M, Videla C, Carballal G, Garcia-Barreno B, Melero JA, Palomo C (2003) Major changes in the G protein of human respiratory syncytial virus isolates introduced by a duplication of 60 nucleotides. J Gen Virol 84(11):3115–3120

    Article  CAS  PubMed  Google Scholar 

  • Tripp RA, Jones LP, Haynes LM, Zheng H, Murphy PM, Anderson LJ (2001) CX3C chemokine mimicry by respiratory syncytial virus G glycoprotein. Nat Immunol 2(8):732–738

    Article  CAS  PubMed  Google Scholar 

  • Villenave R, Thavagnanam S, Sarlang S, Parker J, Douglas I, Skibinski G, Heaney LG, McKaigue JP, Coyle PV, Shields MD, Power UF (2012) In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo. Proc Natl Acad Sci USA 109(13):5040–5045

    Article  CAS  PubMed  Google Scholar 

  • Walsh EE, Hruska J (1983) Monoclonal antibodies to respiratory syncytial virus proteins: identification of the fusion protein. J Virol 47(1):171–177

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wertz GW, Collins PL, Huang Y, Gruber C, Levine S, Ball LA (1985) Nucleotide sequence of the G protein gene of human respiratory syncytial virus reveals an unusual type of viral membrane protein. Proc Natl Acad Sci USA 82(12):4075–4079

    Article  CAS  PubMed  Google Scholar 

  • Whitehead SS, Bukreyev A, Teng MN, Firestone C-Y, St. Claire M, Elkins WR, Collins PL, Murphy BR (1999) Recombinant respiratory syncytial virus bearing a deletion of either the NS2 or SH gene is attenuated in chimpanzees. J Virol 73(4):3438–3442

    Google Scholar 

  • Wild C, Greenwell T, Matthews T (1993) A synthetic peptide from HIV-1 gp41 is a potent inhibitor of virus-mediated cell–cell fusion. AIDS Res Hum Retroviruses 9(11):1051–1053

    Article  CAS  PubMed  Google Scholar 

  • Wild C, Oas T, McDanal C, Bolognesi D, Matthews T (1992) A synthetic peptide inhibitor of human immunodeficiency virus replication: correlation between solution structure and viral inhibition. Proc Natl Acad Sci USA 89(21):10537–10541

    Article  CAS  PubMed  Google Scholar 

  • Wu H, Pfarr DS, Johnson S, Brewah YA, Woods RM, Patel NK, White WI, Young JF, Kiener PA (2007a) Development of motavizumab, an ultra-potent antibody for the prevention of respiratory syncytial virus infection in the upper and lower respiratory tract. J Mol Biol 368(3):652–665

    Article  CAS  PubMed  Google Scholar 

  • Wu S-J, Schmidt A, Beil EJ, Day ND, Branigan PJ, Liu C, Gutshall LL, Palomo C, Furze J, Taylor G, Melero JA, Tsui P, Del Vecchio AM, Kruszynski M (2007b) Characterization of the epitope for anti-human respiratory syncytial virus F protein monoclonal antibody 101F using synthetic peptides and genetic approaches. J Gen Virol 88(10):2719–2723

    Article  CAS  PubMed  Google Scholar 

  • Yin HS, Wen X, Paterson RG, Lamb RA, Jardetzky TS (2006) Structure of the parainfluenza virus 5 F protein in its metastable, prefusion conformation. Nature 439(7072):38–44

    Article  CAS  PubMed  Google Scholar 

  • Zhang L, Bukreyev A, Thompson CI, Watson B, Peeples ME, Collins PL, Pickles RJ (2005) Infection of ciliated cells by human parainfluenza virus type 3 in an in vitro model of human airway epithelium. J Virol 79(2):1113–1124

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang L, Peeples ME, Boucher RC, Collins PL, Pickles RJ (2002) Respiratory syncytial virus infection of human airway epithelial cells is polarized, specific to ciliated cells, and without obvious cytopathology. J Virol 76(11):5654–5666

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhao X, Singh M, Malashkevich VN, Kim PS (2000) Structural characterization of the human respiratory syncytial virus fusion protein core. Proc Natl Acad Sci USA 97(26):14172–14177

    Article  CAS  PubMed  Google Scholar 

  • Zimmer G, Budz L, Herrler G (2001a) Proteolytic activation of respiratory syncytial virus fusion protein. Cleavage at two furin consensus sequences. J Biol Chem 276(34):31642–31650

    Article  CAS  PubMed  Google Scholar 

  • Zimmer G, Trotz I, Herrler G (2001b) N-glycans of F protein differentially affect fusion activity of human respiratory syncytial virus. J Virol 75(10):4744–4751

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Supranee Chaiwatpongskorn and Jacqueline Corry for their help with the graphics. Authors are supported by NIH grants AI095684 (MEP and WCR) and AI093848 (MEP), Tibotec/Johnson & Johnson (MEP) and Cystic Fibrosis Foundation Therapeutics, Inc. (MEP).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mark E. Peeples .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

McLellan, J.S., Ray, W.C., Peeples, M.E. (2013). Structure and Function of Respiratory Syncytial Virus Surface Glycoproteins. In: Anderson, L., Graham, B. (eds) Challenges and Opportunities for Respiratory Syncytial Virus Vaccines. Current Topics in Microbiology and Immunology, vol 372. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-38919-1_4

Download citation

Publish with us

Policies and ethics