Skip to main content
Top
Published in: Archives of Virology 10/2015

01-10-2015 | Original Article

Effect of amino acid sequence variations at position 149 on the fusogenic activity of the subtype B avian metapneumovirus fusion protein

Authors: Bingling Yun, Yanni Gao, Yongzhen Liu, Xiaolu Guan, Yongqiang Wang, Xiaole Qi, Honglei Gao, Changjun Liu, Hongyu Cui, Yanping Zhang, Yulong Gao, Xiaomei Wang

Published in: Archives of Virology | Issue 10/2015

Login to get access

Abstract

The entry of enveloped viruses into host cells requires the fusion of viral and cell membranes. These membrane fusion reactions are mediated by virus-encoded glycoproteins. In the case of avian metapneumovirus (aMPV), the fusion (F) protein alone can mediate virus entry and induce syncytium formation in vitro. To investigate the fusogenic activity of the aMPV F protein, we compared the fusogenic activities of three subtypes of aMPV F proteins using a TCSD50 assay developed in this study. Interestingly, we found that the F protein of aMPV subtype B (aMPV/B) strain VCO3/60616 (aMPV/vB) was hyperfusogenic when compared with F proteins of aMPV/B strain aMPV/f (aMPV/fB), aMPV subtype A (aMPV/A), and aMPV subtype C (aMPV/C). We then further demonstrated that the amino acid (aa) residue 149F contributed to the hyperfusogenic activity of the aMPV/vB F protein. Moreover, we revealed that residue 149F had no effect on the fusogenic activities of aMPV/A, aMPV/C, and human metapneumovirus (hMPV) F proteins. Collectively, we provide the first evidence that the amino acid at position 149 affects the fusogenic activity of the aMPV/B F protein, and our findings will provide new insights into the fusogenic mechanism of this protein.
Literature
1.
go back to reference Earp L, Delos S, Park H, White J (2005) The many mechanisms of viral membrane fusion proteins. Membrane trafficking in viral replication. Springer, Berlin, pp 25–66CrossRef Earp L, Delos S, Park H, White J (2005) The many mechanisms of viral membrane fusion proteins. Membrane trafficking in viral replication. Springer, Berlin, pp 25–66CrossRef
2.
go back to reference Moore J, Jameson BA, Weiss RA, Sattentau Q (1993) The HIV-cell fusion reaction. Viral fusion mechanisms. CRC Press, Boca Raton, pp 233–289 Moore J, Jameson BA, Weiss RA, Sattentau Q (1993) The HIV-cell fusion reaction. Viral fusion mechanisms. CRC Press, Boca Raton, pp 233–289
3.
go back to reference Nussbaum O, Broder CC, Berger EA (1994) Fusogenic mechanisms of enveloped-virus glycoproteins analyzed by a novel recombinant vaccinia virus-based assay quantitating cell fusion-dependent reporter gene activation. J Virol 68:5411–5422PubMedCentralPubMed Nussbaum O, Broder CC, Berger EA (1994) Fusogenic mechanisms of enveloped-virus glycoproteins analyzed by a novel recombinant vaccinia virus-based assay quantitating cell fusion-dependent reporter gene activation. J Virol 68:5411–5422PubMedCentralPubMed
4.
go back to reference Zaitsev V, von Itzstein M, Groves D, Kiefel M, Takimoto T, Portner A, Taylor G (2004) Second sialic acid binding site in Newcastle disease virus hemagglutinin-neuraminidase: implications for fusion. J Virol 78:3733–3741PubMedCentralCrossRefPubMed Zaitsev V, von Itzstein M, Groves D, Kiefel M, Takimoto T, Portner A, Taylor G (2004) Second sialic acid binding site in Newcastle disease virus hemagglutinin-neuraminidase: implications for fusion. J Virol 78:3733–3741PubMedCentralCrossRefPubMed
5.
go back to reference Chen L, Gorman JJ, McKimm-Breschkin J, Lawrence LJ, Tulloch PA, Smith BJ, Colman PM, Lawrence MC (2001) The structure of the fusion glycoprotein of Newcastle disease virus suggests a novel paradigm for the molecular mechanism of membrane fusion. Structure 9:255–266CrossRefPubMed Chen L, Gorman JJ, McKimm-Breschkin J, Lawrence LJ, Tulloch PA, Smith BJ, Colman PM, Lawrence MC (2001) The structure of the fusion glycoprotein of Newcastle disease virus suggests a novel paradigm for the molecular mechanism of membrane fusion. Structure 9:255–266CrossRefPubMed
6.
go back to reference Plemper RK, Lakdawala AS, Gernert KM, Snyder JP, Compans RW (2003) Structural features of paramyxovirus F protein required for fusion initiation. Biochemistry 42:6645–6655CrossRefPubMed Plemper RK, Lakdawala AS, Gernert KM, Snyder JP, Compans RW (2003) Structural features of paramyxovirus F protein required for fusion initiation. Biochemistry 42:6645–6655CrossRefPubMed
7.
go back to reference Bagai S, Lamb RA (1995) Quantitative measurement of paramyxovirus fusion: differences in requirements of glycoproteins between simian virus 5 and human parainfluenza virus 3 or Newcastle disease virus. J Virol 69:6712–6719PubMedCentralPubMed Bagai S, Lamb RA (1995) Quantitative measurement of paramyxovirus fusion: differences in requirements of glycoproteins between simian virus 5 and human parainfluenza virus 3 or Newcastle disease virus. J Virol 69:6712–6719PubMedCentralPubMed
8.
go back to reference Porotto M, Murrell M, Greengard O, Moscona A (2003) Triggering of human parainfluenza virus 3 fusion protein (F) by the hemagglutinin-neuraminidase (HN) protein: an HN mutation diminishes the rate of F activation and fusion. J Virol 77:3647–3654PubMedCentralCrossRefPubMed Porotto M, Murrell M, Greengard O, Moscona A (2003) Triggering of human parainfluenza virus 3 fusion protein (F) by the hemagglutinin-neuraminidase (HN) protein: an HN mutation diminishes the rate of F activation and fusion. J Virol 77:3647–3654PubMedCentralCrossRefPubMed
9.
go back to reference Aguilar HC, Ataman ZA, Aspericueta V, Fang AQ, Stroud M, Negrete OA, Kammerer RA, Lee B (2009) A novel receptor-induced activation site in the Nipah virus attachment glycoprotein (G) involved in triggering the fusion glycoprotein (F). J Biol Chem 284:1628–1635PubMedCentralCrossRefPubMed Aguilar HC, Ataman ZA, Aspericueta V, Fang AQ, Stroud M, Negrete OA, Kammerer RA, Lee B (2009) A novel receptor-induced activation site in the Nipah virus attachment glycoprotein (G) involved in triggering the fusion glycoprotein (F). J Biol Chem 284:1628–1635PubMedCentralCrossRefPubMed
10.
go back to reference Talekar A, DeVito I, Salah Z, Palmer SG, Chattopadhyay A, Rose JK, Xu R, Wilson IA, Moscona A, Porotto M (2013) Identification of a region in the stalk domain of the Nipah virus receptor binding protein that is critical for fusion activation. J Virol 87:10980–10996PubMedCentralCrossRefPubMed Talekar A, DeVito I, Salah Z, Palmer SG, Chattopadhyay A, Rose JK, Xu R, Wilson IA, Moscona A, Porotto M (2013) Identification of a region in the stalk domain of the Nipah virus receptor binding protein that is critical for fusion activation. J Virol 87:10980–10996PubMedCentralCrossRefPubMed
11.
go back to reference Pastey MK, Crowe JE, Graham BS (1999) RhoA interacts with the fusion glycoprotein of respiratory syncytial virus and facilitates virus-induced syncytium formation. J Virol 73:7262–7270PubMedCentralPubMed Pastey MK, Crowe JE, Graham BS (1999) RhoA interacts with the fusion glycoprotein of respiratory syncytial virus and facilitates virus-induced syncytium formation. J Virol 73:7262–7270PubMedCentralPubMed
12.
go back to reference Herfst S, Mas V, Ver LS, Wierda RJ, Osterhaus AD, Fouchier RA, Melero JA (2008) Low-pH-induced membrane fusion mediated by human metapneumovirus F protein is a rare, strain-dependent phenomenon. J Virol 82:8891–8895PubMedCentralCrossRefPubMed Herfst S, Mas V, Ver LS, Wierda RJ, Osterhaus AD, Fouchier RA, Melero JA (2008) Low-pH-induced membrane fusion mediated by human metapneumovirus F protein is a rare, strain-dependent phenomenon. J Virol 82:8891–8895PubMedCentralCrossRefPubMed
13.
go back to reference Schowalter RM, Chang A, Robach JG, Buchholz UJ, Dutch RE (2009) Low-pH triggering of human metapneumovirus fusion: essential residues and importance in entry. J Virol 83:1511–1522PubMedCentralCrossRefPubMed Schowalter RM, Chang A, Robach JG, Buchholz UJ, Dutch RE (2009) Low-pH triggering of human metapneumovirus fusion: essential residues and importance in entry. J Virol 83:1511–1522PubMedCentralCrossRefPubMed
14.
go back to reference Schickli JH, Kaur J, Ulbrandt N, Spaete RR, Tang RS (2005) An S101P substitution in the putative cleavage motif of the human metapneumovirus fusion protein is a major determinant for trypsin-independent growth in Vero cells and does not alter tissue tropism in hamsters. J Virol 79:10678–10689PubMedCentralCrossRefPubMed Schickli JH, Kaur J, Ulbrandt N, Spaete RR, Tang RS (2005) An S101P substitution in the putative cleavage motif of the human metapneumovirus fusion protein is a major determinant for trypsin-independent growth in Vero cells and does not alter tissue tropism in hamsters. J Virol 79:10678–10689PubMedCentralCrossRefPubMed
15.
go back to reference Ito M, Nishio M, Kawano M, Kusagawa S, Komada H, Ito Y, Tsurudome M (1997) Role of a single amino acid at the amino terminus of the simian virus 5 F2 subunit in syncytium formation. J Virol 71:9855–9858PubMedCentralPubMed Ito M, Nishio M, Kawano M, Kusagawa S, Komada H, Ito Y, Tsurudome M (1997) Role of a single amino acid at the amino terminus of the simian virus 5 F2 subunit in syncytium formation. J Virol 71:9855–9858PubMedCentralPubMed
16.
go back to reference Dutch RE, Joshi SB, Lamb RA (1998) Membrane fusion promoted by increasing surface densities of the paramyxovirus F and HN proteins: comparison of fusion reactions mediated by simian virus 5 F, human parainfluenza virus type 3 F, and influenza virus HA. J Virol 72:7745–7753PubMedCentralPubMed Dutch RE, Joshi SB, Lamb RA (1998) Membrane fusion promoted by increasing surface densities of the paramyxovirus F and HN proteins: comparison of fusion reactions mediated by simian virus 5 F, human parainfluenza virus type 3 F, and influenza virus HA. J Virol 72:7745–7753PubMedCentralPubMed
17.
go back to reference Biacchesi S, Skiadopoulos MH, Yang L, Lamirande EW, Tran KC, Murphy BR, Collins PL, Buchholz UJ (2004) Recombinant human metapneumovirus lacking the small hydrophobic SH and/or attachment G glycoprotein: deletion of G yields a promising vaccine candidate. J Virol 78:12877–12887PubMedCentralCrossRefPubMed Biacchesi S, Skiadopoulos MH, Yang L, Lamirande EW, Tran KC, Murphy BR, Collins PL, Buchholz UJ (2004) Recombinant human metapneumovirus lacking the small hydrophobic SH and/or attachment G glycoprotein: deletion of G yields a promising vaccine candidate. J Virol 78:12877–12887PubMedCentralCrossRefPubMed
18.
19.
go back to reference Cook JKA, Ellis MM, Huggins MB (1991) The pathogenesis of turkey rhinotracheitis virus in turkey poults inoculated with the virus alone or together with two strains of bacteria. Avian Pathol 20:155–166CrossRefPubMed Cook JKA, Ellis MM, Huggins MB (1991) The pathogenesis of turkey rhinotracheitis virus in turkey poults inoculated with the virus alone or together with two strains of bacteria. Avian Pathol 20:155–166CrossRefPubMed
20.
go back to reference Senne D, Edson R, Pedersen J, Panigrahy B (1997) Avian pneumovirus update. In: Proceedings of 134th annual convention of the American Veterinary Medical Association, Reno, p 190 Senne D, Edson R, Pedersen J, Panigrahy B (1997) Avian pneumovirus update. In: Proceedings of 134th annual convention of the American Veterinary Medical Association, Reno, p 190
21.
go back to reference Buys S, Du Preez J (1980) A preliminary report on the isolation of a virus causing sinusitis in turkeys in South Africa and attempts to attenuate the virus. Turkeys 28:36 Buys S, Du Preez J (1980) A preliminary report on the isolation of a virus causing sinusitis in turkeys in South Africa and attempts to attenuate the virus. Turkeys 28:36
22.
go back to reference Bäyon-Auboyer MH, Arnauld C, Toquin D, Eterradossi N (2000) Nucleotide sequences of the F, L and G protein genes of two non-A/non-B avian pneumoviruses (APV) reveal a novel APV subgroup. J Gen Virol 81:2723–2733CrossRefPubMed Bäyon-Auboyer MH, Arnauld C, Toquin D, Eterradossi N (2000) Nucleotide sequences of the F, L and G protein genes of two non-A/non-B avian pneumoviruses (APV) reveal a novel APV subgroup. J Gen Virol 81:2723–2733CrossRefPubMed
23.
go back to reference Seal BS (1998) Matrix protein gene nucleotide and predicted amino acid sequence demonstrate that the first US avian pneumovirus isolate is distinct from European strains. Virus Res 58:45–52CrossRefPubMed Seal BS (1998) Matrix protein gene nucleotide and predicted amino acid sequence demonstrate that the first US avian pneumovirus isolate is distinct from European strains. Virus Res 58:45–52CrossRefPubMed
24.
go back to reference Wei L, Zhu S, Yan X, Wang J, Zhang C, Liu S, She R, Hu F, Quan R, Liu J (2013) Avian metapneumovirus subgroup C infection in chickens, China. Emerg Infect Dis 19:1092PubMedCentralCrossRefPubMed Wei L, Zhu S, Yan X, Wang J, Zhang C, Liu S, She R, Hu F, Quan R, Liu J (2013) Avian metapneumovirus subgroup C infection in chickens, China. Emerg Infect Dis 19:1092PubMedCentralCrossRefPubMed
25.
go back to reference Mase M, Yamaguchi S, Tsukamoto K, Imada T, Imai K, Nakamura K (2003) Presence of avian pneumovirus subtypes A and B in Japan. Avian Dis 47:481–484CrossRefPubMed Mase M, Yamaguchi S, Tsukamoto K, Imada T, Imai K, Nakamura K (2003) Presence of avian pneumovirus subtypes A and B in Japan. Avian Dis 47:481–484CrossRefPubMed
26.
go back to reference Kwon JS, Lee HJ, Jeong SH, Park JY, Hong YH, Lee YJ, Youn HS, Lee DW, Do SH, Park SY (2010) Isolation and characterization of avian metapneumovirus from chickens in Korea. J Vet Sci 11:59PubMedCentralCrossRefPubMed Kwon JS, Lee HJ, Jeong SH, Park JY, Hong YH, Lee YJ, Youn HS, Lee DW, Do SH, Park SY (2010) Isolation and characterization of avian metapneumovirus from chickens in Korea. J Vet Sci 11:59PubMedCentralCrossRefPubMed
27.
go back to reference Banet-Noach C, Simanov L, Perk S (2005) Characterization of Israeli avian metapneumovirus strains in turkeys and chickens. Avian Pathol 34:220–226CrossRefPubMed Banet-Noach C, Simanov L, Perk S (2005) Characterization of Israeli avian metapneumovirus strains in turkeys and chickens. Avian Pathol 34:220–226CrossRefPubMed
28.
go back to reference D’Arce RC, Coswig LT, Almeida RS, Trevisol IM, Monteiro MC, Rossini LI, Di Fabio J, Hafez HM, Arns CW (2005) Subtyping of new Brazilian avian metapneumovirus isolates from chickens and turkeys by reverse transcriptase-nested-polymerase chain reaction. Avian Pathol 34:133–136CrossRefPubMed D’Arce RC, Coswig LT, Almeida RS, Trevisol IM, Monteiro MC, Rossini LI, Di Fabio J, Hafez HM, Arns CW (2005) Subtyping of new Brazilian avian metapneumovirus isolates from chickens and turkeys by reverse transcriptase-nested-polymerase chain reaction. Avian Pathol 34:133–136CrossRefPubMed
29.
go back to reference Maharaj S, Thomson D, Graca JV (1994) Isolation of an avian pneumovirus like agent from broiler breeder chickens in South Africa. Vet Rec 134:525–526CrossRefPubMed Maharaj S, Thomson D, Graca JV (1994) Isolation of an avian pneumovirus like agent from broiler breeder chickens in South Africa. Vet Rec 134:525–526CrossRefPubMed
30.
go back to reference Bäyon-Auboyer M, Jestin V, Toquin D, Cherbonnel M, Eterradossi N (1999) Comparison of F-, G-and N-based RT-PCR protocols with conventional virological procedures for the detection and typing of turkey rhinotracheitis virus. Arch Virol 144:1091–1109CrossRefPubMed Bäyon-Auboyer M, Jestin V, Toquin D, Cherbonnel M, Eterradossi N (1999) Comparison of F-, G-and N-based RT-PCR protocols with conventional virological procedures for the detection and typing of turkey rhinotracheitis virus. Arch Virol 144:1091–1109CrossRefPubMed
31.
go back to reference Dar AM, Tune K, Munir S, Panigrahy B, Goyal SM, Kapur V (2001) PCR-based detection of an emerging avian pneumovirus in US turkey flocks. J Vet Diagn Invest 13:201–205CrossRefPubMed Dar AM, Tune K, Munir S, Panigrahy B, Goyal SM, Kapur V (2001) PCR-based detection of an emerging avian pneumovirus in US turkey flocks. J Vet Diagn Invest 13:201–205CrossRefPubMed
32.
go back to reference Coswig LT, Santos MBd, Hafez HM, Ferreira HL, Arns CW (2010) Propagation of avian metapneumovirus subtypes A and B using chicken embryo related and other cell systems. J Virol Methods 167:1–4CrossRefPubMed Coswig LT, Santos MBd, Hafez HM, Ferreira HL, Arns CW (2010) Propagation of avian metapneumovirus subtypes A and B using chicken embryo related and other cell systems. J Virol Methods 167:1–4CrossRefPubMed
33.
go back to reference de Graaf M, Schrauwen EJA, Herfst S, van Amerongen G, Osterhaus ADME, Fouchier RAM (2009) Fusion protein is the main determinant of metapneumovirus host tropism. J Gen Virol 90:1408–1416CrossRefPubMed de Graaf M, Schrauwen EJA, Herfst S, van Amerongen G, Osterhaus ADME, Fouchier RAM (2009) Fusion protein is the main determinant of metapneumovirus host tropism. J Gen Virol 90:1408–1416CrossRefPubMed
34.
go back to reference Wei Y, Feng K, Yao X, Cai H, Li J, Mirza AM, Iorio RM, Li J (2012) Localization of a region in the fusion protein of avian metapneumovirus that modulates cell–cell fusion. J Virol 86:11800–11814PubMedCentralCrossRefPubMed Wei Y, Feng K, Yao X, Cai H, Li J, Mirza AM, Iorio RM, Li J (2012) Localization of a region in the fusion protein of avian metapneumovirus that modulates cell–cell fusion. J Virol 86:11800–11814PubMedCentralCrossRefPubMed
35.
go back to reference Avitabile E, Lombardi G, Gianni T, Capri M, Campadelli-Fiume G (2004) Coexpression of UL20p and gK inhibits cell–cell fusion mediated by herpes simplex virus glycoproteins gD, gH-gL, and wild-type gB or an endocytosis-defective gB mutant and downmodulates their cell surface expression. J Virol 78:8015–8025PubMedCentralCrossRefPubMed Avitabile E, Lombardi G, Gianni T, Capri M, Campadelli-Fiume G (2004) Coexpression of UL20p and gK inhibits cell–cell fusion mediated by herpes simplex virus glycoproteins gD, gH-gL, and wild-type gB or an endocytosis-defective gB mutant and downmodulates their cell surface expression. J Virol 78:8015–8025PubMedCentralCrossRefPubMed
37.
go back to reference Horvath C, Paterson R, Shaughnessy M, Wood R, Lamb R (1992) Biological activity of paramyxovirus fusion proteins: factors influencing formation of syncytia. J Virol 66:4564–4569PubMedCentralPubMed Horvath C, Paterson R, Shaughnessy M, Wood R, Lamb R (1992) Biological activity of paramyxovirus fusion proteins: factors influencing formation of syncytia. J Virol 66:4564–4569PubMedCentralPubMed
38.
go back to reference Heminway BR, Yang Y, Galinski MS (1994) Paramyxovirus mediated cell fusion requires co-expression of both the fusion and hemagglutinin-neuraminidase glycoproteins. Virus Res 31:1–16CrossRefPubMed Heminway BR, Yang Y, Galinski MS (1994) Paramyxovirus mediated cell fusion requires co-expression of both the fusion and hemagglutinin-neuraminidase glycoproteins. Virus Res 31:1–16CrossRefPubMed
39.
go back to reference Schowalter RM, Smith SE, Dutch RE (2006) Characterization of human metapneumovirus F protein-promoted membrane fusion: critical roles for proteolytic processing and low pH. J Virol 80:10931–10941PubMedCentralCrossRefPubMed Schowalter RM, Smith SE, Dutch RE (2006) Characterization of human metapneumovirus F protein-promoted membrane fusion: critical roles for proteolytic processing and low pH. J Virol 80:10931–10941PubMedCentralCrossRefPubMed
40.
go back to reference Reed LJ, Muench H (1938) A simple method of estimating fifty per cent endpoints. Am J Epidemiol 27:493–497 Reed LJ, Muench H (1938) A simple method of estimating fifty per cent endpoints. Am J Epidemiol 27:493–497
41.
go back to reference Sugiyama M, Ito H, Hata Y, Ono E, Ito T (2010) Complete nucleotide sequences of avian metapneumovirus subtype B genome. Virus genes 41:389–395CrossRefPubMed Sugiyama M, Ito H, Hata Y, Ono E, Ito T (2010) Complete nucleotide sequences of avian metapneumovirus subtype B genome. Virus genes 41:389–395CrossRefPubMed
42.
go back to reference Liman M, Rautenschlein S (2007) Induction of local and systemic immune reactions following infection of turkeys with avian Metapneumovirus (aMPV) subtypes A and B. Vet Immunol Immunopathol 115:273–285CrossRefPubMed Liman M, Rautenschlein S (2007) Induction of local and systemic immune reactions following infection of turkeys with avian Metapneumovirus (aMPV) subtypes A and B. Vet Immunol Immunopathol 115:273–285CrossRefPubMed
Metadata
Title
Effect of amino acid sequence variations at position 149 on the fusogenic activity of the subtype B avian metapneumovirus fusion protein
Authors
Bingling Yun
Yanni Gao
Yongzhen Liu
Xiaolu Guan
Yongqiang Wang
Xiaole Qi
Honglei Gao
Changjun Liu
Hongyu Cui
Yanping Zhang
Yulong Gao
Xiaomei Wang
Publication date
01-10-2015
Publisher
Springer Vienna
Published in
Archives of Virology / Issue 10/2015
Print ISSN: 0304-8608
Electronic ISSN: 1432-8798
DOI
https://doi.org/10.1007/s00705-015-2524-x

Other articles of this Issue 10/2015

Archives of Virology 10/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine