viral fusion proteins


Summary: Proteins, usually glycoproteins, found in the viral envelopes of a variety of viruses. They promote cell membrane fusion and thereby may function in the uptake of the virus by cells.

Top Publications

  1. Diederich S, Sauerhering L, Weis M, Altmeppen H, Schaschke N, Reinheckel T, et al. Activation of the Nipah virus fusion protein in MDCK cells is mediated by cathepsin B within the endosome-recycling compartment. J Virol. 2012;86:3736-45 pubmed publisher
    ..In summary, this study shows for the first time that endosomal cathepsin B can play a functional role in the activation of highly pathogenic NiV...
  2. Park M, Matsuura H, Lamb R, Barron A, Jardetzky T. A fluorescence polarization assay using an engineered human respiratory syncytial virus F protein as a direct screening platform. Anal Biochem. 2011;409:195-201 pubmed publisher
    ..We anticipate that this new 5HB system will provide an effective tool to identify and study potential antivirals to control hRSV infection. ..
  3. Samal S, Kumar S, Khattar S, Samal S. A single amino acid change, Q114R, in the cleavage-site sequence of Newcastle disease virus fusion protein attenuates viral replication and pathogenicity. J Gen Virol. 2011;92:2333-8 pubmed publisher
    ..The pathogenicity was further reduced when the isoleucine at position 118 was substituted for valine. ..
  4. Farzan S, Palermo L, Yokoyama C, Orefice G, Fornabaio M, Sarkar A, et al. Premature activation of the paramyxovirus fusion protein before target cell attachment with corruption of the viral fusion machinery. J Biol Chem. 2011;286:37945-54 pubmed publisher
    ..This first evidence that activation of a paramyxovirus F can be specifically induced before the virus contacts its target cell suggests a new strategy with broad implications for the design of antiviral agents. ..
  5. Cosset F, Lavillette D. Cell entry of enveloped viruses. Adv Genet. 2011;73:121-83 pubmed publisher
    ..These pseudoparticles are suitable for high-throughput screenings that help in the development of natural or artificial inhibitors as new therapeutics of the class of entry inhibitors. ..
  6. Subbiah M, Khattar S, Collins P, Samal S. Mutations in the fusion protein cleavage site of avian paramyxovirus serotype 2 increase cleavability and syncytium formation but do not increase viral virulence in chickens. J Virol. 2011;85:5394-405 pubmed publisher
    ..Furthermore, cleavage of the F protein is not a determinant of APMV-2 pathogenicity in chickens...
  7. Smith E, Culler M, Hellman L, Fried M, Creamer T, Dutch R. Beyond anchoring: the expanding role of the hendra virus fusion protein transmembrane domain in protein folding, stability, and function. J Virol. 2012;86:3003-13 pubmed publisher
    While work with viral fusion proteins has demonstrated that the transmembrane domain (TMD) can affect protein folding, stability, and membrane fusion promotion, the mechanism(s) remains poorly understood...
  8. Goto Sugai K, Tsukagoshi H, Mizuta K, Matsuda S, Noda M, Sugai T, et al. Genotyping and phylogenetic analysis of the major genes in respiratory syncytial virus isolated from infants with bronchiolitis. Jpn J Infect Dis. 2010;63:393-400 pubmed
    ..These results suggest that RSV genotypes GA2 and BA may be associated with bronchiolitis in the cases studied here. ..
  9. Plemper R, Brindley M, Iorio R. Structural and mechanistic studies of measles virus illuminate paramyxovirus entry. PLoS Pathog. 2011;7:e1002058 pubmed publisher
    ..Here, we review these advances in our molecular understanding of MeV entry in the context of diverse entry strategies employed by other members of the paramyxovirus family. ..

Scientific Experts

More Information


  1. Brindley M, Plemper R. Blue native PAGE and biomolecular complementation reveal a tetrameric or higher-order oligomer organization of the physiological measles virus attachment protein H. J Virol. 2010;84:12174-84 pubmed publisher
    ..Results are interpreted in light of a model in which receptor binding may affect the oligomeric organization of the attachment protein complex. ..
  2. Radu G, Caidi H, Miao C, Tripp R, Anderson L, Haynes L. 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. 2010;84:9632-6 pubmed publisher
    ..It is possible that antibodies with similar reactivities might prevent enhanced disease and improve the safety of nonlive virus vaccines. ..
  3. Mas V, Herfst S, Osterhaus A, Fouchier R, Melero J. Residues of the human metapneumovirus fusion (F) protein critical for its strain-related fusion phenotype: implications for the virus replication cycle. J Virol. 2011;85:12650-61 pubmed publisher
    ..J. Virol. 83:1511-1522, 2009) highlight the relevance of certain residues in the linker region and domain II of the pretriggered hMPV F protein for the process of membrane fusion. ..
  4. Langereis M, van Vliet A, Boot W, de Groot R. Attachment of mouse hepatitis virus to O-acetylated sialic acid is mediated by hemagglutinin-esterase and not by the spike protein. J Virol. 2010;84:8970-4 pubmed publisher
    ..Apparently, expansion of group A betacoronaviruses into new hosts and niches was accompanied by changes in HE ligand and substrate preference and in the roles of HE and S in Sia receptor usage...
  5. Porotto M, Devito I, Palmer S, Jurgens E, Yee J, Yokoyama C, et al. Spring-loaded model revisited: paramyxovirus fusion requires engagement of a receptor binding protein beyond initial triggering of the fusion protein. J Virol. 2011;85:12867-80 pubmed publisher
    ..This model has broad implications for the mechanism of paramyxovirus fusion and for strategies to prevent viral entry...
  6. Porotto M, Palmer S, Palermo L, Moscona A. Mechanism of fusion triggering by human parainfluenza virus type III: communication between viral glycoproteins during entry. J Biol Chem. 2012;287:778-93 pubmed publisher
    ..This first evidence for the sequence of initial events that lead to viral entry may indicate a new paradigm for understanding Paramyxovirus infection. ..
  7. Tirumurugaan K, Kapgate S, Vinupriya M, Vijayarani K, Kumanan K, Elankumaran S. Genotypic and pathotypic characterization of Newcastle disease viruses from India. PLoS ONE. 2011;6:e28414 pubmed publisher
    ..Genotype IV strains are considered to have "died out" after the first panzootic (1926-1960) of ND. But, our results suggest that there is persistence of genotype IV strains in India. ..
  8. Shabbir M, Abbas M, Yaqub T, Mukhtar N, Subhani A, Habib H, et al. Genetic analysis of Newcastle disease virus from Punjab, Pakistan. Virus Genes. 2013;46:309-15 pubmed publisher
    ..From these results, in conjunction with our recent reports of NDV from Pakistan, it is possible to conclude that emergence of novel group may require revisiting the diagnostics and vaccine control strategies. ..
  9. Münch R, Mühlebach M, Schaser T, Kneissl S, Jost C, Plückthun A, et al. DARPins: an efficient targeting domain for lentiviral vectors. Mol Ther. 2011;19:686-93 pubmed publisher
    ..Thus, DARPins are a promising alternative to scFvs for retargeting of LVs. ..
  10. McLellan J, Chen M, Leung S, Graepel K, Du X, Yang Y, et al. Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody. Science. 2013;340:1113-7 pubmed publisher
    ..These studies should enable design of improved vaccine antigens and define new targets for passive prevention of RSV-induced disease. ..
  11. Kim S, Subbiah M, Samuel A, Collins P, Samal S. Roles of the fusion and hemagglutinin-neuraminidase proteins in replication, tropism, and pathogenicity of avian paramyxoviruses. J Virol. 2011;85:8582-96 pubmed publisher
  12. Zhu Q, Patel N, McAuliffe J, Zhu W, Wachter L, McCarthy M, et al. Natural polymorphisms and resistance-associated mutations in the fusion protein of respiratory syncytial virus (RSV): effects on RSV susceptibility to palivizumab. J Infect Dis. 2012;205:635-8 pubmed publisher
    ..Polymorphisms were identified at low frequency, and only polymorphic mutations in antigenic site A (<1% of all polymorphisms) conferred palivizumab resistance...
  13. Kim Y, Donald J, Grigoryan G, Leser G, Fadeev A, Lamb R, et al. Capture and imaging of a prehairpin fusion intermediate of the paramyxovirus PIV5. Proc Natl Acad Sci U S A. 2011;108:20992-7 pubmed publisher
  14. Zokarkar A, Lamb R. The paramyxovirus fusion protein C-terminal region: mutagenesis indicates an indivisible protein unit. J Virol. 2012;86:2600-9 pubmed publisher
    ..Alanine scanning mutagenesis of MPER indicates that it has a regulatory role in fusion since both hyperfusogenic and hypofusogenic mutations were found. ..
  15. Gravel K, McGinnes L, Reitter J, Morrison T. The transmembrane domain sequence affects the structure and function of the Newcastle disease virus fusion protein. J Virol. 2011;85:3486-97 pubmed publisher
    ..These results show that the specific sequence of the TM domain of the NDV F protein is important for the conformation of the preactivation form of the ectodomain, the interactions of the protein with HN protein, and fusion activity...
  16. Popa A, Pager C, Dutch R. C-terminal tyrosine residues modulate the fusion activity of the Hendra virus fusion protein. Biochemistry. 2011;50:945-52 pubmed publisher
    ..In addition, our results implicate C-terminal tyrosine residues in the modulation of the membrane fusion reaction promoted by these viral glycoproteins. ..
  17. Libersou S, Albertini A, Ouldali M, Maury V, Maheu C, Raux H, et al. Distinct structural rearrangements of the VSV glycoprotein drive membrane fusion. J Cell Biol. 2010;191:199-210 pubmed publisher
    ..We suggest that the formation of these arrays, which have been shown to be an intrinsic property of the G ectodomain, induces membrane constraints, achieving the fusion reaction. ..
  18. Huang K, Incognito L, Cheng X, Ulbrandt N, Wu H. Respiratory syncytial virus-neutralizing monoclonal antibodies motavizumab and palivizumab inhibit fusion. J Virol. 2010;84:8132-40 pubmed publisher
    ..Based on models developed from numerous studies of viral fusion proteins, our results indicate that these antibodies may prevent conformational changes in F protein required for ..
  19. Swanson K, Wen X, Leser G, Paterson R, Lamb R, Jardetzky T. Structure of the Newcastle disease virus F protein in the post-fusion conformation. Virology. 2010;402:372-9 pubmed publisher
    ..Electrostatic and temperature factor analysis of the F structures points to regions of these proteins that may be functionally important in their membrane fusion activity...
  20. Perozo F, Marcano R, Afonso C. Biological and phylogenetic characterization of a genotype VII Newcastle disease virus from Venezuela: efficacy of field vaccination. J Clin Microbiol. 2012;50:1204-8 pubmed publisher
    ..Overall, results confirmed the presence of the genotype VII viruses in South America and suggest that field-associated factors such as immunosuppression compromise the efficacy of the vaccination protocols implemented. ..
  21. Chang A, Masante C, Buchholz U, Dutch R. Human metapneumovirus (HMPV) binding and infection are mediated by interactions between the HMPV fusion protein and heparan sulfate. J Virol. 2012;86:3230-43 pubmed publisher
  22. Xiao S, Khattar S, Subbiah M, Collins P, Samal S. Mutation of the f-protein cleavage site of avian paramyxovirus type 7 results in furin cleavage, fusion promotion, and increased replication in vitro but not increased replication, tissue tropism, or virulence in chickens. J Virol. 2012;86:3828-38 pubmed publisher
    ..Thus, the acquisition of furin cleavability by APMV-7 resulted in syncytium formation and increased virus yield in vitro but did not alter virus yield, tropism, or virulence in chickens. ..
  23. Chang S, Shih A, Tang Y, Chang W. Vaccinia mature virus fusion regulator A26 protein binds to A16 and G9 proteins of the viral entry fusion complex and dissociates from mature virions at low pH. J Virol. 2012;86:3809-18 pubmed publisher
    ..Finally, we provide evidence that acid (pH 4.7) treatment induced A26 protein and A26-A27 protein complexes of 70 kDa and 90 kDa to dissociate from mature virions, suggesting that the structure of A26 protein is acid sensitive...
  24. Porotto M, Salah Z, Devito I, Talekar A, Palmer S, Xu R, et al. The second receptor binding site of the globular head of the Newcastle disease virus hemagglutinin-neuraminidase activates the stalk of multiple paramyxovirus receptor binding proteins to trigger fusion. J Virol. 2012;86:5730-41 pubmed publisher
    ..We suggest a general model for paramyxovirus fusion activation in which receptor engagement at site II plays an active role in F activation...
  25. Chen P, Song Z, Qi Y, Feng X, Xu N, Sun Y, et al. Molecular determinants of enterovirus 71 viral entry: cleft around GLN-172 on VP1 protein interacts with variable region on scavenge receptor B 2. J Biol Chem. 2012;287:6406-20 pubmed publisher
    ..6). These studies elucidated the viral capsid and receptor determinants of enterovirus 71 infection and revealed a possible target for antiviral interventions...
  26. Choi Y, Mason C, Jones L, Crabtree J, Jorquera P, Tripp R. 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. 2012;25:193-203 pubmed publisher
    ..These findings suggest that vaccines that induce RSV G protein-CX3CR1 blocking antibodies may provide a disease intervention strategy in the efforts to develop safe and efficacious RSV vaccines. ..
  27. Chang A, Hackett B, Winter C, Buchholz U, Dutch R. Potential electrostatic interactions in multiple regions affect human metapneumovirus F-mediated membrane fusion. J Virol. 2012;86:9843-53 pubmed publisher
    ..As a whole, these studies implicate charged residues and potential electrostatic interactions in function, pH sensing, and overall stability of HMPV F...
  28. Cox R, Livesay S, Johnson M, Ohi M, Williams J. The human metapneumovirus fusion protein mediates entry via an interaction with RGD-binding integrins. J Virol. 2012;86:12148-60 pubmed publisher
    ..These results suggest a stepwise mechanism of HMPV entry mediated by the F protein through its interactions with cellular receptors, including RGD-binding integrins...
  29. Bose S, Zokarkar A, Welch B, Leser G, Jardetzky T, Lamb R. Fusion activation by a headless parainfluenza virus 5 hemagglutinin-neuraminidase stalk suggests a modular mechanism for triggering. Proc Natl Acad Sci U S A. 2012;109:E2625-34 pubmed
  30. Quan F, Kim Y, Lee S, Yi H, Kang S, Bozja J, et al. Viruslike particle vaccine induces protection against respiratory syncytial virus infection in mice. J Infect Dis. 2011;204:987-95 pubmed publisher
    ..Despite decades of research with traditional or subunit vaccine approaches, there are no approved RSV vaccines. New approaches are therefore urgently needed to develop effective RSV vaccines...
  31. Igonet S, Vaney M, Vonrhein C, Vonhrein C, Bricogne G, Stura E, et al. X-ray structure of the arenavirus glycoprotein GP2 in its postfusion hairpin conformation. Proc Natl Acad Sci U S A. 2011;108:19967-72 pubmed publisher
    ..8-Å resolution. The structure shows the characteristic trimeric coiled coil present in class I viral fusion proteins, with a central stutter that allows a close structural alignment with most of the available structures of ..
  32. Hoque M, Burgess G, Karo Karo D, Cheam A, Skerratt L. Monitoring of wild birds for Newcastle disease virus in north Queensland, Australia. Prev Vet Med. 2012;103:49-62 pubmed publisher
    ..3 and 4). Our findings of higher prevalence in PWDs along with confirmation of class-one and class-two type NDV RNAs will significantly contribute to the design of surveillance programs for NDVs in northern Australia. ..
  33. Swanson K, Settembre E, Shaw C, Dey A, Rappuoli R, Mandl C, et al. Structural basis for immunization with postfusion respiratory syncytial virus fusion F glycoprotein (RSV F) to elicit high neutralizing antibody titers. Proc Natl Acad Sci U S A. 2011;108:9619-24 pubmed publisher
    ..This unanticipated structural feature explains the engineered RSV F antigen's efficiency as an immunogen. This work illustrates how structural-based antigen design can guide the rational optimization of candidate vaccine antigens...
  34. Backovic M, Jardetzky T. Class III viral membrane fusion proteins. Adv Exp Med Biol. 2011;714:91-101 pubmed publisher
    Members of class III of viral fusion proteins share common structural features and molecular architecture, although they belong to evolutionary distant viruses and carry no sequence homology...
  35. Kim S, Jang J, Yu J, Chang J. Single mucosal immunization of recombinant adenovirus-based vaccine expressing F1 protein fragment induces protective mucosal immunity against respiratory syncytial virus infection. Vaccine. 2010;28:3801-8 pubmed publisher
    ..Taken together, our data demonstrate that a single intranasal administration of rAd/F1co is sufficient for the protection and represents a promising prophylactic vaccination regimen against RSV infection. ..
  36. Porotto M, Rockx B, Yokoyama C, Talekar A, Devito I, Palermo L, et al. Inhibition of Nipah virus infection in vivo: targeting an early stage of paramyxovirus fusion activation during viral entry. PLoS Pathog. 2010;6:e1001168 pubmed publisher
    ..The in vivo efficacy of cholesterol-tagged peptides, and in particular their ability to penetrate the CNS, suggests that they are promising candidates for the prevention or therapy of infection by Nipah and other lethal paramyxoviruses. ..
  37. McGinnes L, Gravel K, Finberg R, Kurt Jones E, Massare M, Smith G, et al. Assembly and immunological properties of Newcastle disease virus-like particles containing the respiratory syncytial virus F and G proteins. J Virol. 2011;85:366-77 pubmed publisher
    ..These results suggest that these VLPs are effective RSV vaccines in mice, in contrast to other nonreplicating RSV vaccine candidates. ..
  38. Hamelin M, Gagnon C, Prince G, Kiener P, Suzich J, Ulbrandt N, et al. Prophylactic and therapeutic benefits of a monoclonal antibody against the fusion protein of human metapneumovirus in a mouse model. Antiviral Res. 2010;88:31-7 pubmed publisher
    ..Both prophylactic and, to a lesser extent, therapeutic administration of MAb 338 improved acute and late consequences of HMPV infection in a relevant mouse model...
  39. Blanco J, Boukhvalova M, Shirey K, Prince G, Vogel S. New insights for development of a safe and protective RSV vaccine. Hum Vaccin. 2010;6:482-92 pubmed
    ..A safe and efficacious vaccine for RSV will require "re-education" of the host immune response against RSV to prevent vaccine-enhanced or severe RSV disease. ..
  40. Hu Z, Hu S, Meng C, Wang X, Zhu J, Liu X. Generation of a genotype VII Newcastle disease virus vaccine candidate with high yield in embryonated chicken eggs. Avian Dis. 2011;55:391-7 pubmed
    ..Taken together, these results suggest that NDV/AI4 can provide better protection than LaSota and is a promising vaccine candidate against genotype VII NDV...
  41. Porotto M, Salah Z, Gui L, Devito I, Jurgens E, Lu H, et al. Regulation of paramyxovirus fusion activation: the hemagglutinin-neuraminidase protein stabilizes the fusion protein in a pretriggered state. J Virol. 2012;86:12838-48 pubmed publisher
    ..The results indicate that HN helps stabilize the prefusion state of F, and analysis of a stalk domain mutant HN reveals that the stalk domain of HN mediates the F-stabilization effect...
  42. Markosyan R, Cohen F. Negative potentials across biological membranes promote fusion by class II and class III viral proteins. Mol Biol Cell. 2010;21:2001-12 pubmed publisher
    ..In the hemifused state, virions that fused exhibited slower lipid transfer than did nonfusing virions. All viruses with class II or III fusion proteins may utilize voltage to achieve infection. ..
  43. Magro M, Andreu D, Gomez Puertas P, Melero J, Palomo C. Neutralization of human respiratory syncytial virus infectivity by antibodies and low-molecular-weight compounds targeted against the fusion glycoprotein. J Virol. 2010;84:7970-82 pubmed publisher
    ..In contrast, the peptide F478-516 or BMS-433771 must bind to F protein intermediates generated during virus-cell membrane fusion, blocking further development of this process. ..
  44. Chang A, Dutch R. Paramyxovirus fusion and entry: multiple paths to a common end. Viruses. 2012;4:613-36 pubmed publisher
    ..Finally, we highlight key unanswered questions and how further studies can identify novel targets for the development of therapeutic treatments against these human pathogens. ..
  45. Steffen D, Xu K, Nikolov D, Broder C. Henipavirus mediated membrane fusion, virus entry and targeted therapeutics. Viruses. 2012;4:280-308 pubmed publisher
    ..Finally, recent candidate therapeutics for henipavirus-mediated disease are summarized in light of their ability to inhibit HeV and NiV entry by targeting their G and F glycoproteins. ..
  46. Magro M, Mas V, Chappell K, Vázquez M, Cano O, Luque D, et al. Neutralizing antibodies against the preactive form of respiratory syncytial virus fusion protein offer unique possibilities for clinical intervention. Proc Natl Acad Sci U S A. 2012;109:3089-94 pubmed publisher
    ..These antibodies therefore offer unique possibilities for immune intervention against hRSV, and their production should be assessed in trials of hRSV vaccines...
  47. Langereis M, Zeng Q, Heesters B, Heesters B, Huizinga E, de Groot R. The murine coronavirus hemagglutinin-esterase receptor-binding site: a major shift in ligand specificity through modest changes in architecture. PLoS Pathog. 2012;8:e1002492 pubmed publisher
    ..Our findings illustrate the ease with which viruses can change receptor-binding specificity with potential consequences for host-, organ and/or cell tropism, and for pathogenesis. ..
  48. Lundin A, Bergstrom T, Bendrioua L, Kann N, Adamiak B, Trybala E. Two novel fusion inhibitors of human respiratory syncytial virus. Antiviral Res. 2010;88:317-24 pubmed publisher
  49. Papenburg J, Carbonneau J, Hamelin M, Isabel S, Bouhy X, Ohoumanne N, et al. Molecular evolution of respiratory syncytial virus fusion gene, Canada, 2006-2010. Emerg Infect Dis. 2012;18:120-4 pubmed publisher
    ..Resistance-conferring mutations within the palivizumab binding site occurred in 8.7% of palivizumab recipients and none of the nonrecipients. ..
  50. Chaiwatpongsakorn S, Epand R, Collins P, Epand R, Peeples M. Soluble respiratory syncytial virus fusion protein in the fully cleaved, pretriggered state is triggered by exposure to low-molarity buffer. J Virol. 2011;85:3968-77 pubmed publisher
    ..Mutation of the furin cleavage site adjacent to the fusion peptide prevented liposome association, further confirming that association is via the fusion peptide. ..
  51. Bukreyev A, Yang L, Fricke J, Cheng L, Ward J, Murphy B, et al. 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. 2008;82:12191-204 pubmed publisher
    ..Thus, sG helps RSV escape the antibody-dependent restriction of replication via effects as an antigen decoy and as a modulator of leukocytes bearing Fc gamma receptors. ..
  52. Cattoli G, Fusaro A, Monne I, Molia S, Le Menach A, Maregeya B, et al. Emergence of a new genetic lineage of Newcastle disease virus in West and Central Africa--implications for diagnosis and control. Vet Microbiol. 2010;142:168-76 pubmed publisher
    ..The present investigation provides important information on the epidemiology, diagnosis and control of NDV in Africa and highlights the importance of supporting surveillance in developing countries for transboundary animal diseases...
  53. Ulbrandt N, Ji H, Patel N, Barnes A, Wilson S, Kiener P, et al. Identification of antibody neutralization epitopes on the fusion protein of human metapneumovirus. J Gen Virol. 2008;89:3113-8 pubmed publisher
    ..This suggests that these homologous regions play important, conserved functions in both viruses...