Localization Analysis of Heterophilic Antigen Epitopes of H1N1 Influenza Virus Hemagglutinin
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Previous studies have indicated that two monoclonal antibodies (mAbs; A1-10 and H1-84) of the hemagglutinin (HA) antigen on the H1N1 influenza virus cross-react with human brain tissue. It has been proposed that there are heterophilic epitopes between the HA protein and human brain tissue (Guo et al. in Immunobiology 220:941–946, 2015). However, characterisation of the two mAbs recognising the heterophilic epitope on HA has not yet been performed. In the present study, the common antigens of influenza virus HA were confirmed using indirect enzyme-linked immunosorbent assays and analysed with DNAMAN software. The epitopes were localized to nine peptides in the influenza virus HA sequence and the distribution of the peptides in the three-dimensional structure of HA was determined using PyMOL software. Key amino acids and variable sequences of the antibodies were identified using abYsis software. The results demonstrated that there were a number of common antigens among the five influenza viruses studied that were recognised by the mAbs. One of the peptides, P2 (LVLWGIHHP191–199), bound both of the mAbs and was located in the head region of HA. The key amino acids of this epitope and the variable regions in the heavy and light chain sequences of the mAbs that recognised the epitope are described. A heterophilic epitope on H1N1 influenza virus HA was also introduced. The existence of this epitope provides a novel perspective for the occurrence of nervous system diseases that could be caused by influenza virus infection, which might aid in influenza prevention and control.
KeywordsH1N1 influenza virus HA antigen Monoclonal antibody Localization Heterophilic epitope
This work was supported by The National Key Research and Development Program of China (Grant No. 2016YFD0500700), The Natural Science Basic Research Program of Shaanxi Province (Grant No. 2016JM8065) and Shaanxi Provincial People’s Hospital Incubation Fund Program (Grant No. 2015YX-4).
CG, XX and LS designed the experiments. CG, JZ, HL, DL, QF, YL and YF conducted the experiments. CG and JH analyzed the data. CG and HZ wrote the paper. All authors approved the final manuscript.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no competing interests.
Animal and Human Rights Statement
This article does not include any experiments that involve human or animal subjects.
- Ahmed SS, Volkmuth W, Duca J, Corti L, Pallaoro M, Pezzicoli A, Karle A, Rigat F, Rappuoli R, Narasimhan V, Julkunen I, Vuorela A, Vaarala O, Nohynek H, Pasini FL, Montomoli E, Trombetta C, Adams CM, Rothbard J, Steinman L (2015) Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2. Sci Transl Med 7:294ra105CrossRefGoogle Scholar
- Cong YJ, Ren FZ, Yun ZY (2010) Identification of Ig E-binding β-epitopes on β-lactoglobulin. Food Sci 15:190–193 (in Chinese) Google Scholar
- de Wit E, Siegers JY, Cronin JM, Weatherman S, van den Brand JM, Leijten LM, van Run P, Begeman L, van den Ham HJ, Andeweg AC, Bushmaker T, Scott DP, Saturday G, Munster VJ, Feldmann H, van Riel D (2018) 1918 H1N1 influenza virus replicates and induces proinflammatory cytokine responses in extrarespiratory tissues of ferrets. J Infect Dis 217:1237–1246CrossRefGoogle Scholar
- Forssman J (1911) Die Herstellung hochwertiger spezifischer Schafha¨monysine ohne Verwendung von Schafblut. Ein Beitrag zur Lehre von heterologer Antiko¨rpebildung. Biochem Z 37:78–115 (in German) Google Scholar
- Gong X, Yin H, Shi YH, Guan SS, He XQ, Yang L, Yu YJ, Kuai ZY, Jiang CL, Kong W, Wang S, Shan YM (2016) Conserved stem fragment from H3 influenza hemagglutinin elicits cross-clade neutralizing antibodies through stalk-targeted blocking of conformational change during membrane fusion. Immunol Lett 172:11–20CrossRefGoogle Scholar
- Hu B, Wei YQ (2004) Molecular mimicry associated with infection, autoimmunity, and tumor immunotherapy. Chin Bull Life Sci 16:66–72 (in Chinese) Google Scholar
- Hurwitz ES, Nelson DB, Davis C, Morens D, Schonberger LB (1982) National surveillance for Reye syndrome: a five-year review. Pediatrics 70:895–900Google Scholar
- Ishida Y, Kawashima H, Morichi S, Yamanaka G, Okumura A, Nakagawa S, Morishima T (2015) Brain magnetic resonance imaging in acute phase of pandemic influenza A (H1N1)2009-associated encephalopathy in children. Neuropediatrics 46:20–25Google Scholar
- Li Y, Hu HY, Qi ZL, Sun JY, Li Y, Feng Q, Guo CY, Wang HF, Zhao PH, Liu Y, Zhao XR, Wang GH, Zhang H, Liu L, Hu J (2018) Identification and characterization of epitopes from influenza A virus hemagglutinin that induce broadly cross-reactive antibodies. Int J Mol Med 41:1673–1682Google Scholar
- Seow J, Morales RA, MacRaild CA, Krishnarjuna B, McGowan S, Dingjan T, Jaipuria G, Rouet R, Wilde KL, Atreya HS, Richards JS, Anders RF, Christ D, Drinkwater N, Norton RS (2017) Structure and characterisation of a key epitope in the conserved C-terminal domain of the malaria vaccine candidate MSP2. J Mol Biol 429:836–846CrossRefGoogle Scholar
- Srinivasappa J, Saegusa J, Prabhakar BS, Gentry MK, Buchmeier MJ, Wiktor TJ, Koprowski H, Oldstone MB, Notkins AL (1986) Molecular mimicry: frequency of reactivity of monoclonal antiviral antibodies with normal tissues. J Virol 57:397–401Google Scholar
- Taylor DN, Treanor JJ, Strout C, Johnson C, Fitzgerald T, Kavita U, Ozer K, Tussey L, Shaw A (2011) Induction of a potent immune response in the elderly using the TLR-5 agonist, flagellin, with a recombinant hemagglutinin influenza-flagellin fusion vaccine (VAX125, STF2. HA1 SI). Vaccine 29:4897–4902CrossRefGoogle Scholar
- Wang JJ, Yang GX, Zhang WC, Lu L, Tsuneyama K, Kronenberg M, Véla JL, Lopez-Hoyos M, He XS, Ridgway WM, Leung PS, Gershwin ME (2014) Escherichia coli infection induces autoimmune cholangitis and anti-mitochondrialantibodies in non-obese diabetic (NOD).B6 (Idd10/Idd18) mice. Clin Exp Immunol 175:192–201CrossRefGoogle Scholar