The Vestigial Esterase Domain of Haemagglutinin of H5N1 Avian Influenza A Virus: Antigenicity and Contribution to Viral Pathogenesis
Abstract
:1. Introduction
2. Discussion
2.1. Localisation of VE in the Three-Dimensional (3D) Structure of HA of H5N1
2.2. Generation of Neutralising mAbs Binding to the VE Subdomain of H5N1
2.3. In Vivo Studies of VE-Binding mAbs
2.4. Role of Residues within VE in Regulating HA Protein Acid Stability
3. Conclusions
Funding
Conflicts of Interest
References
- Garten, W.; Klenk, H.D. Understanding influenza virus pathogenicity. Trends Microbiol. 1999, 7, 99–100. [Google Scholar] [CrossRef]
- Skehel, J.J.; Wiley, D.C. Receptor binding and membrane fusion in virus entry: The influenza hemagglutinin. Annu. Rev. Biochem. 2000, 69, 531–569. [Google Scholar] [CrossRef] [PubMed]
- Webby, R. Understanding immune responses to the influenza vaccine. Nat. Med. 2016, 22, 1387–1388. [Google Scholar] [CrossRef] [PubMed]
- Mameli, C.; D’auria, E.; Erba, P.; Nannini, P.; Zuccotti, G.V. Influenza Vaccine Response: Future Perspectives; Taylor & Francis: Oxfordshire, UK, 2018. [Google Scholar]
- Wu, N.C.; Wilson, I.A. Structural insights into the design of novel anti-influenza therapies. Nat. Struct. Mol. Biol. 2018, 25, 115–121. [Google Scholar] [CrossRef] [PubMed]
- Sparrow, E.; Friede, M.; Sheikh, M.; Torvaldsen, S.; Newall, A.T. Passive immunization for influenza through antibody therapies, a review of the pipeline, challenges and potential applications. Vaccine 2016, 34, 5442–5448. [Google Scholar] [CrossRef] [PubMed]
- Neu, K.E.; Dunand, C.J.H.; Wilson, P.C. Heads, stalks and everything else: How can antibodies eradicate influenza as a human disease? Curr. Opin. Immunol. 2016, 42, 48–55. [Google Scholar] [CrossRef] [PubMed]
- Corti, D.; Cameroni, E.; Guarino, B.; Kallewaard, N.L.; Zhu, Q.; Lanzavecchia, A. Tackling influenza with broadly neutralizing antibodies. Curr. Opin. Virol. 2017, 24, 60–69. [Google Scholar] [CrossRef] [PubMed]
- Velkov, T.; Ong, C.; Baker, M.A.; Kim, H.; Li, J.; Nation, R.L.; Huang, J.X.; Cooper, M.A.; Rockman, S. The antigenic architecture of the hemagglutinin of influenza H5N1 viruses. Mol. Immunol. 2013, 56, 705–719. [Google Scholar] [CrossRef] [PubMed]
- Ren, H.; Zhou, P. Epitope-focused vaccine design against influenza A and B viruses. Curr. Opin. Immunol. 2016, 42, 83–90. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Paul, S.S.; Mok, C.K.; Mak, T.M.; Ng, O.W.; Aboagye, J.O.; Wohlbold, T.J.; Krammer, F.; Tan, Y.J. A cross-clade H5N1 influenza a virus neutralizing monoclonal antibody binds to a novel epitope within the vestigial esterase domain of hemagglutinin. Antivir. Res. 2017, 144, 299–310. [Google Scholar] [CrossRef] [PubMed]
- Qian, M.; Hu, H.; Zuo, T.; Wang, G.; Zhang, L.; Zhou, P. Unraveling of a neutralization mechanism by two human antibodies against conserved epitopes in the globular head of H5 hemagglutinin. J. Virol. 2013, 87, 3571–3577. [Google Scholar] [CrossRef] [PubMed]
- Ren, H.; Wang, G.; Wang, S.; Chen, H.; Chen, Z.; Hu, H.; Cheng, G.; Zhou, P. Cross-protection of newly emerging HPAI H5 viruses by neutralizing human monoclonal antibodies: A viable alternative to oseltamivir. MAbs 2016, 8, 1156–1166. [Google Scholar] [CrossRef] [PubMed]
- Zhu, X.; Guo, Y.H.; Jiang, T.; Wang, Y.D.; Chan, K.H.; Li, X.F.; Yu, W.; McBride, R.; Paulson, J.C.; Yuen, K.Y.; et al. A unique and conserved neutralization epitope in H5N1 influenza viruses identified by an antibody against the a/goose/guangdong/1/96 hemagglutinin. J. Virol. 2013, 87, 12619–12635. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.; Qi, X.; Zhang, Q.; Zeng, X.; Shi, Z.; Jin, Q.; Zhan, F.; Xu, Y.; Liu, Z.; Feng, Z.; et al. Human 4F5 single-chain Fv antibody recognizing a conserved HA1 epitope has broad neutralizing potency against H5N1 influenza A viruses of different clades. Antivir. Res. 2013, 99, 91–99. [Google Scholar] [CrossRef] [PubMed]
- Rosenthal, P.B.; Zhang, X.; Formanowski, F.; Fitz, W.; Wong, C.H.; Meier-Ewert, H.; Skehel, J.J.; Wiley, D.C. Structure of the haemagglutinin-esterase-fusion glycoprotein of influenza c virus. Nature 1998, 396, 92–96. [Google Scholar] [CrossRef] [PubMed]
- Herrler, G.; Klenk, H.-D. Structure and function of the HEF glycoprotein of influenza C virus. In Advances in Virus Research; Elsevier: New York, NY, USA, 1991; Volume 40, pp. 213–234. [Google Scholar]
- Ha, Y.; Stevens, D.J.; Skehel, J.J.; Wiley, D.C. H5 avian and H9 swine influenza virus haemagglutinin structures: Possible origin of influenza subtypes. EMBO J. 2002, 21, 865–875. [Google Scholar] [CrossRef] [PubMed]
- Shen, S.; Mahadevappa, G.; Oh, H.L.; Wee, B.Y.; Choi, Y.W.; Hwang, L.A.; Lim, S.G.; Hong, W.; Lal, S.K.; Tan, Y.J. Comparing the antibody responses against recombinant hemagglutinin proteins of avian influenza a (H5N1) virus expressed in insect cells and bacteria. J. Med. Virol. 2008, 80, 1972–1983. [Google Scholar] [CrossRef] [PubMed]
- Oh, H.L.; Akerstrom, S.; Shen, S.; Bereczky, S.; Karlberg, H.; Klingstrom, J.; Lal, S.K.; Mirazimi, A.; Tan, Y.J. An antibody against a novel and conserved epitope in the hemagglutinin 1 subunit neutralizes numerous H5N1 influenza viruses. J. Virol. 2010, 84, 8275–8286. [Google Scholar] [CrossRef] [PubMed]
- Mak, T.M.; Hanson, B.J.; Tan, Y.J. Chimerization and characterization of a monoclonal antibody with potent neutralizing activity across multiple influenza a H5N1 clades. Antivir. Res. 2014, 107, 76–83. [Google Scholar] [CrossRef] [PubMed]
- Xiong, F.; Xia, L.; Wang, J.; Wu, B.; Wang, D.; Yuan, L.; Cheng, Y.; Zhu, H.; Che, X.; Zhang, Q.; et al. A high-affinity CDR-grafted antibody against influenza a H5N1 viruses recognizes a conserved epitope of H5 hemagglutinin. PLoS ONE 2014, 9, e88777. [Google Scholar] [CrossRef] [PubMed]
- Hu, H.; Voss, J.; Zhang, G.; Buchy, P.; Zuo, T.; Wang, L.; Wang, F.; Zhou, F.; Wang, G.; Tsai, C.; et al. A human antibody recognizing a conserved epitope of H5 hemagglutinin broadly neutralizes highly pathogenic avian influenza H5N1 viruses. J. Virol. 2012, 86, 2978–2989. [Google Scholar] [CrossRef] [PubMed]
- Wu, L. WHO China statement on H5N6. Available online: http://www.wpro.who.int/china/mediacentre/releases/2014/20140507/en/ (accessed on 19 June 2018).
- Forthal, D.N. Functions of antibodies. Microbiol. Spectr. 2014, 2, 1–17. [Google Scholar] [PubMed]
- Mullarkey, C.E.; Bailey, M.J.; Golubeva, D.A.; Tan, G.S.; Nachbagauer, R.; He, W.; Novakowski, K.E.; Bowdish, D.M.; Miller, M.S.; Palese, P. Broadly neutralizing hemagglutinin stalk-specific antibodies induce potent phagocytosis of immune complexes by neutrophils in an Fc-dependent manner. MBio 2016, 7, e01624-16. [Google Scholar] [CrossRef] [PubMed]
- DiLillo, D.J.; Tan, G.S.; Palese, P.; Ravetch, J.V. Broadly neutralizing hemagglutinin stalk-specific antibodies require fcgammar interactions for protection against influenza virus in vivo. Nat. Med. 2014, 20, 143–151. [Google Scholar] [CrossRef] [PubMed]
- Jegaskanda, S.; Reading, P.C.; Kent, S.J. Influenza-specific antibody-dependent cellular cytotoxicity: Toward a universal influenza vaccine. J. Immunol. 2014, 193, 469–475. [Google Scholar] [CrossRef] [PubMed]
- Jegaskanda, S.; Vanderven, H.A.; Wheatley, A.K.; Kent, S.J. Fc or not Fc; that is the question: Antibody Fc-receptor interactions are key to universal influenza vaccine design. Hum. Vaccines Immunother. 2017, 13, 1288–1296. [Google Scholar] [CrossRef] [PubMed][Green Version]
- He, W.; Tan, G.S.; Mullarkey, C.E.; Lee, A.J.; Lam, M.M.; Krammer, F.; Henry, C.; Wilson, P.C.; Ashkar, A.A.; Palese, P.; et al. Epitope specificity plays a critical role in regulating antibody-dependent cell-mediated cytotoxicity against influenza a virus. Proc. Natl. Acad. Sci. USA 2016, 113, 11931–11936. [Google Scholar] [CrossRef] [PubMed]
- Wang, S.; Ren, H.; Jiang, W.; Chen, H.; Hu, H.; Chen, Z.; Zhou, P. Divergent requirement of Fc-Fγ receptor interactions for in vivo protection against influenza viruses by two pan-H5 hemagglutinin antibodies. J. Virol. 2017, 91, e02065-16. [Google Scholar] [CrossRef] [PubMed]
- Bangaru, S.; Zhang, H.; Gilchuk, I.M.; Voss, T.G.; Irving, R.P.; Gilchuk, P.; Matta, P.; Zhu, X.; Lang, S.; Nieusma, T. A multifunctional human monoclonal neutralizing antibody that targets a unique conserved epitope on influenza HA. Nat. Commun. 2018, 9, 2669. [Google Scholar] [CrossRef] [PubMed]
- Tan, G.S.; Leon, P.E.; Albrecht, R.A.; Margine, I.; Hirsh, A.; Bahl, J.; Krammer, F. Broadly-reactive neutralizing and non-neutralizing antibodies directed against the h7 influenza virus hemagglutinin reveal divergent mechanisms of protection. PLoS Pathog. 2016, 12, e1005578. [Google Scholar] [CrossRef] [PubMed]
- Chai, N.; Swem, L.R.; Park, S.; Nakamura, G.; Chiang, N.; Estevez, A.; Fong, R.; Kamen, L.; Kho, E.; Reichelt, M.; et al. A broadly protective therapeutic antibody against influenza B virus with two mechanisms of action. Nat. Commun. 2017, 8, 14234. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Dreyfus, C.; Laursen, N.S.; Kwaks, T.; Zuijdgeest, D.; Khayat, R.; Ekiert, D.C.; Lee, J.H.; Metlagel, Z.; Bujny, M.V.; Jongeneelen, M.; et al. Highly conserved protective epitopes on influenza b viruses. Science 2012, 337, 1343–1348. [Google Scholar] [CrossRef] [PubMed]
- Xiong, X.; McCauley, J.W.; Steinhauer, D.A. Receptor binding properties of the influenza virus hemagglutinin as a determinant of host range. In Influenza Pathogenesis and Control-Volume I; Springer: New York, NY, USA, 2014; pp. 63–91. [Google Scholar]
- Shi, Y.; Wu, Y.; Zhang, W.; Qi, J.; Gao, G.F. Enabling the ‘host jump’: Structural determinants of receptor-binding specificity in influenza a viruses. Nat. Rev. Microbiol. 2014, 12, 822–831. [Google Scholar] [CrossRef] [PubMed]
- De Graaf, M.; Fouchier, R.A. Role of receptor binding specificity in influenza a virus transmission and pathogenesis. EMBO J. 2014, 33, 823–841. [Google Scholar] [CrossRef] [PubMed]
- Mair, C.M.; Ludwig, K.; Herrmann, A.; Sieben, C. Receptor binding and pH stability—How influenza A virus hemagglutinin affects host-specific virus infection. Biochim. Biophys. Acta 2014, 1838, 1153–1168. [Google Scholar] [CrossRef] [PubMed]
- Daidoji, T.; Watanabe, Y.; Arai, Y.; Kajikawa, J.; Hirose, R.; Nakaya, T. Unique infectious strategy of H5N1 avian influenza virus is governed by the acid-destabilized property of hemagglutinin. Viral Immunol. 2017, 30, 398–407. [Google Scholar] [CrossRef] [PubMed]
- OIE. Avian Influenza (Infection with Avian Influenza Viruses). Terrestrial Animal Health Code; Biological Standards Commission, World Organization for Animal Health: Paris, France, 2009; pp. 1–20. [Google Scholar]
- Hulse, D.J.; Webster, R.G.; Russell, R.J.; Perez, D.R. Molecular determinants within the surface proteins involved in the pathogenicity of H5N1 influenza viruses in chickens. J. Virol. 2004, 78, 9954–9964. [Google Scholar] [CrossRef] [PubMed]
- DuBois, R.M.; Zaraket, H.; Reddivari, M.; Heath, R.J.; White, S.W.; Russell, C.J. Acid stability of the hemagglutinin protein regulates H5N1 influenza virus pathogenicity. PLoS Pathog. 2011, 7, e1002398. [Google Scholar] [CrossRef] [PubMed]
- Herfst, S.; Schrauwen, E.J.; Linster, M.; Chutinimitkul, S.; de Wit, E.; Munster, V.J.; Sorrell, E.M.; Bestebroer, T.M.; Burke, D.F.; Smith, D.J.; et al. Airborne transmission of influenza A/H5N1 virus between ferrets. Science 2012, 336, 1534–1541. [Google Scholar] [CrossRef] [PubMed]
- Zhang, W.; Shi, Y.; Lu, X.; Shu, Y.; Qi, J.; Gao, G.F. An airborne transmissible avian influenza H5 hemagglutinin seen at the atomic level. Science 2013, 340, 1463–1467. [Google Scholar] [CrossRef] [PubMed]
© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Zheng, Z.; Paul, S.S.; Mo, X.; Yuan, Y.-R.A.; Tan, Y.-J. The Vestigial Esterase Domain of Haemagglutinin of H5N1 Avian Influenza A Virus: Antigenicity and Contribution to Viral Pathogenesis. Vaccines 2018, 6, 53. https://doi.org/10.3390/vaccines6030053
Zheng Z, Paul SS, Mo X, Yuan Y-RA, Tan Y-J. The Vestigial Esterase Domain of Haemagglutinin of H5N1 Avian Influenza A Virus: Antigenicity and Contribution to Viral Pathogenesis. Vaccines. 2018; 6(3):53. https://doi.org/10.3390/vaccines6030053
Chicago/Turabian StyleZheng, Zhiqiang, Subha Sankar Paul, Xiaobing Mo, Yu-Ren Adam Yuan, and Yee-Joo Tan. 2018. "The Vestigial Esterase Domain of Haemagglutinin of H5N1 Avian Influenza A Virus: Antigenicity and Contribution to Viral Pathogenesis" Vaccines 6, no. 3: 53. https://doi.org/10.3390/vaccines6030053