Abstract
We have selected ligands for Puumala hantavirus, the causative agent of nephropathia epidemica, from a seven-amino-acid peptide library flanked by cysteines and displayed on a filamentous phage. To direct the selection to areas on the virus particle which are essential for infection, phages were competitively eluted with neutralizing monoclonal antibodies specific for the viral glycoproteins. The selected phage populations were specific for the same sites as the antibodies and mimicked their functions. The peptide insert, CHWMFSPWC, when displayed on the phages, completely inhibited Puumala virus infection in cell culture at the same effective concentration as the eluting antibody specific for envelope glycoprotein G2. The binding of the phage clones to the virus and inhibition of infection were not necessarily coincident; Pro-6 was critical for virus inhibition, while consensus residues Trp-2 and Phe-4 were essential for binding. The strategy described can be applied to any virus for production of molecules mimicking the effect of neutralizing antibodies.
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- Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
- Antoniadis A., Stylianakis A., Papa A., Alexiou-Daniel S., Lampropoulos A., Nichol S. T., Peters C. J., Spiropoulou C. F. Direct genetic detection of Dobrava virus in Greek and Albanian patients with hemorrhagic fever with renal syndrome. J Infect Dis. 1996 Aug;174(2):407–410. doi: 10.1093/infdis/174.2.407. [DOI] [PubMed] [Google Scholar]
- Arikawa J., Schmaljohn A. L., Dalrymple J. M., Schmaljohn C. S. Characterization of Hantaan virus envelope glycoprotein antigenic determinants defined by monoclonal antibodies. J Gen Virol. 1989 Mar;70(Pt 3):615–624. doi: 10.1099/0022-1317-70-3-615. [DOI] [PubMed] [Google Scholar]
- Arikawa J., Yao J. S., Yoshimatsu K., Takashima I., Hashimoto N. Protective role of antigenic sites on the envelope protein of Hantaan virus defined by monoclonal antibodies. Arch Virol. 1992;126(1-4):271–281. doi: 10.1007/BF01309700. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brummer-Korvenkontio M., Manni T., Ukkonen S., Vaheri A. Detection of hemagglutination-inhibiting antibodies in patients with nephropathia epidemica and Korean hemorrhagic fever by using Puumala virus cell culture antigen. J Infect Dis. 1986 May;153(5):997–998. doi: 10.1093/infdis/153.5.997-a. [DOI] [PubMed] [Google Scholar]
- Brummer-Korvenkontio M., Vaheri A., Hovi T., von Bonsdorff C. H., Vuorimies J., Manni T., Penttinen K., Oker-Blom N., Lähdevirta J. Nephropathia epidemica: detection of antigen in bank voles and serologic diagnosis of human infection. J Infect Dis. 1980 Feb;141(2):131–134. doi: 10.1093/infdis/141.2.131. [DOI] [PubMed] [Google Scholar]
- Burton D. R., Barbas C. F., 3rd, Persson M. A., Koenig S., Chanock R. M., Lerner R. A. A large array of human monoclonal antibodies to type 1 human immunodeficiency virus from combinatorial libraries of asymptomatic seropositive individuals. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10134–10137. doi: 10.1073/pnas.88.22.10134. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clackson T., Wells J. A. A hot spot of binding energy in a hormone-receptor interface. Science. 1995 Jan 20;267(5196):383–386. doi: 10.1126/science.7529940. [DOI] [PubMed] [Google Scholar]
- Cosgriff T. M. Mechanisms of disease in Hantavirus infection: pathophysiology of hemorrhagic fever with renal syndrome. Rev Infect Dis. 1991 Jan-Feb;13(1):97–107. doi: 10.1093/clinids/13.1.97. [DOI] [PubMed] [Google Scholar]
- Dente L., Cesareni G., Micheli G., Felici F., Folgori A., Luzzago A., Monaci P., Nicosia A., Delmastro P. Monoclonal antibodies that recognise filamentous phage: tools for phage display technology. Gene. 1994 Oct 11;148(1):7–13. doi: 10.1016/0378-1119(94)90227-5. [DOI] [PubMed] [Google Scholar]
- Domingo G. J., Leatherbarrow R. J., Freeman N., Patel S., Weir M. Synthesis of a mixture of cyclic peptides based on the Bowman-Birk reactive site loop to screen for serine protease inhibitors. Int J Pept Protein Res. 1995 Jul;46(1):79–87. doi: 10.1111/j.1399-3011.1995.tb00585.x. [DOI] [PubMed] [Google Scholar]
- Elliott R. M. Molecular biology of the Bunyaviridae. J Gen Virol. 1990 Mar;71(Pt 3):501–522. doi: 10.1099/0022-1317-71-3-501. [DOI] [PubMed] [Google Scholar]
- Hjelle B., Chavez-Giles F., Torrez-Martinez N., Yates T., Sarisky J., Webb J., Ascher M. Genetic identification of a novel hantavirus of the harvest mouse Reithrodontomys megalotis. J Virol. 1994 Oct;68(10):6751–6754. doi: 10.1128/jvi.68.10.6751-6754.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hong S. S., Boulanger P. Protein ligands of the human adenovirus type 2 outer capsid identified by biopanning of a phage-displayed peptide library on separate domains of wild-type and mutant penton capsomers. EMBO J. 1995 Oct 2;14(19):4714–4727. doi: 10.1002/j.1460-2075.1995.tb00153.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Koivunen E., Gay D. A., Ruoslahti E. Selection of peptides binding to the alpha 5 beta 1 integrin from phage display library. J Biol Chem. 1993 Sep 25;268(27):20205–20210. [PubMed] [Google Scholar]
- Koivunen E., Wang B., Ruoslahti E. Isolation of a highly specific ligand for the alpha 5 beta 1 integrin from a phage display library. J Cell Biol. 1994 Feb;124(3):373–380. doi: 10.1083/jcb.124.3.373. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liang M., Chu Y. K., Schmaljohn C. Bacterial expression of neutralizing mouse monoclonal antibody Fab fragments to Hantaan virus. Virology. 1996 Mar 1;217(1):262–271. doi: 10.1006/viro.1996.0113. [DOI] [PubMed] [Google Scholar]
- Lundkvist A., Fatouros A., Niklasson B. Antigenic variation of European haemorrhagic fever with renal syndrome virus strains characterized using bank vole monoclonal antibodies. J Gen Virol. 1991 Sep;72(Pt 9):2097–2103. doi: 10.1099/0022-1317-72-9-2097. [DOI] [PubMed] [Google Scholar]
- Lundkvist A., Hörling J., Athlin L., Rosén A., Niklasson B. Neutralizing human monoclonal antibodies against Puumala virus, causative agent of nephropathia epidemica: a novel method using antigen-coated magnetic beads for specific B cell isolation. J Gen Virol. 1993 Jul;74(Pt 7):1303–1310. doi: 10.1099/0022-1317-74-7-1303. [DOI] [PubMed] [Google Scholar]
- Lundkvist A., Hörling J., Björsten S., Niklasson B. Sensitive detection of hantaviruses by biotin-streptavidin enhanced immunoassays based on bank vole monoclonal antibodies. J Virol Methods. 1995 Mar;52(1-2):75–86. doi: 10.1016/0166-0934(94)00143-5. [DOI] [PubMed] [Google Scholar]
- Lundkvist A., Hörling J., Niklasson B. The humoral response to Puumala virus infection (nephropathia epidemica) investigated by viral protein specific immunoassays. Arch Virol. 1993;130(1-2):121–130. doi: 10.1007/BF01319001. [DOI] [PubMed] [Google Scholar]
- Lundkvist A., Niklasson B. Bank vole monoclonal antibodies against Puumala virus envelope glycoproteins: identification of epitopes involved in neutralization. Arch Virol. 1992;126(1-4):93–105. doi: 10.1007/BF01309687. [DOI] [PubMed] [Google Scholar]
- Mariniello L., Esposito C., Di Pierro P., Cozzolino A., Pucci P., Porta R. Human-immunodeficiency-virus transmembrane glycoprotein gp41 is an amino acceptor and donor substrate for transglutaminase in vitro. Eur J Biochem. 1993 Jul 1;215(1):99–104. doi: 10.1111/j.1432-1033.1993.tb18011.x. [DOI] [PubMed] [Google Scholar]
- Meulemans E. V., Slobbe R., Wasterval P., Ramaekers F. C., van Eys G. J. Selection of phage-displayed antibodies specific for a cytoskeletal antigen by competitive elution with a monoclonal antibody. J Mol Biol. 1994 Dec 9;244(4):353–360. doi: 10.1006/jmbi.1994.1735. [DOI] [PubMed] [Google Scholar]
- Nichol S. T., Spiropoulou C. F., Morzunov S., Rollin P. E., Ksiazek T. G., Feldmann H., Sanchez A., Childs J., Zaki S., Peters C. J. Genetic identification of a hantavirus associated with an outbreak of acute respiratory illness. Science. 1993 Nov 5;262(5135):914–917. doi: 10.1126/science.8235615. [DOI] [PubMed] [Google Scholar]
- Niklasson B., Jonsson M., Lundkvist A., Horling J., Tkachenko E. Comparison of European isolates of viruses causing hemorrhagic fever with renal syndrome by a neutralization test. Am J Trop Med Hyg. 1991 Dec;45(6):660–665. doi: 10.4269/ajtmh.1991.45.660. [DOI] [PubMed] [Google Scholar]
- O'Neil K. T., Hoess R. H., Jackson S. A., Ramachandran N. S., Mousa S. A., DeGrado W. F. Identification of novel peptide antagonists for GPIIb/IIIa from a conformationally constrained phage peptide library. Proteins. 1992 Dec;14(4):509–515. doi: 10.1002/prot.340140411. [DOI] [PubMed] [Google Scholar]
- Pasqualini R., Koivunen E., Ruoslahti E. A peptide isolated from phage display libraries is a structural and functional mimic of an RGD-binding site on integrins. J Cell Biol. 1995 Sep;130(5):1189–1196. doi: 10.1083/jcb.130.5.1189. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Plyusnin A., Vapalahti O., Vaheri A. Hantaviruses: genome structure, expression and evolution. J Gen Virol. 1996 Nov;77(Pt 11):2677–2687. doi: 10.1099/0022-1317-77-11-2677. [DOI] [PubMed] [Google Scholar]
- Pringle C. R. The Bunyaviridae and their genetics--an overview. Curr Top Microbiol Immunol. 1991;169:1–25. [PubMed] [Google Scholar]
- Schmaljohn C. S., Chu Y. K., Schmaljohn A. L., Dalrymple J. M. Antigenic subunits of Hantaan virus expressed by baculovirus and vaccinia virus recombinants. J Virol. 1990 Jul;64(7):3162–3170. doi: 10.1128/jvi.64.7.3162-3170.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schmaljohn C. S., Hasty S. E., Dalrymple J. M., LeDuc J. W., Lee H. W., von Bonsdorff C. H., Brummer-Korvenkontio M., Vaheri A., Tsai T. F., Regnery H. L. Antigenic and genetic properties of viruses linked to hemorrhagic fever with renal syndrome. Science. 1985 Mar 1;227(4690):1041–1044. doi: 10.1126/science.2858126. [DOI] [PubMed] [Google Scholar]
- Scott J. K., Smith G. P. Searching for peptide ligands with an epitope library. Science. 1990 Jul 27;249(4967):386–390. doi: 10.1126/science.1696028. [DOI] [PubMed] [Google Scholar]
- Smith G. P., Scott J. K. Libraries of peptides and proteins displayed on filamentous phage. Methods Enzymol. 1993;217:228–257. doi: 10.1016/0076-6879(93)17065-d. [DOI] [PubMed] [Google Scholar]
- Stephen C. W., Helminen P., Lane D. P. Characterisation of epitopes on human p53 using phage-displayed peptide libraries: insights into antibody-peptide interactions. J Mol Biol. 1995 Apr 21;248(1):58–78. doi: 10.1006/jmbi.1995.0202. [DOI] [PubMed] [Google Scholar]
- Temonen M., Vapalahti O., Holthöfer H., Brummer-Korvenkontio M., Vaheri A., Lankinen H. Susceptibility of human cells to Puumala virus infection. J Gen Virol. 1993 Mar;74(Pt 3):515–518. doi: 10.1099/0022-1317-74-3-515. [DOI] [PubMed] [Google Scholar]
- Vapalahti O., Kallio-Kokko H., Närvänen A., Julkunen I., Lundkvist A., Plyusnin A., Lehväslaiho H., Brummer-Korvenkontio M., Vaheri A., Lankinen H. Human B-cell epitopes of Puumala virus nucleocapsid protein, the major antigen in early serological response. J Med Virol. 1995 Aug;46(4):293–303. doi: 10.1002/jmv.1890460402. [DOI] [PubMed] [Google Scholar]
- Vapalahti O., Kallio-Kokko H., Salonen E. M., Brummer-Korvenkontio M., Vaheri A. Cloning and sequencing of Puumala virus Sotkamo strain S and M RNA segments: evidence for strain variation in hantaviruses and expression of the nucleocapsid protein. J Gen Virol. 1992 Apr;73(Pt 4):829–838. doi: 10.1099/0022-1317-73-4-829. [DOI] [PubMed] [Google Scholar]
- Wang M., Pennock D. G., Spik K. W., Schmaljohn C. S. Epitope mapping studies with neutralizing and non-neutralizing monoclonal antibodies to the G1 and G2 envelope glycoproteins of Hantaan virus. Virology. 1993 Dec;197(2):757–766. doi: 10.1006/viro.1993.1652. [DOI] [PubMed] [Google Scholar]
- Zaki S. R., Greer P. W., Coffield L. M., Goldsmith C. S., Nolte K. B., Foucar K., Feddersen R. M., Zumwalt R. E., Miller G. L., Khan A. S. Hantavirus pulmonary syndrome. Pathogenesis of an emerging infectious disease. Am J Pathol. 1995 Mar;146(3):552–579. [PMC free article] [PubMed] [Google Scholar]