Abstract
Monoclonal antibodies were used to isolate nonneutralizable antigenic variants in the hemagglutinin-neuraminidase glycoprotein of Newcastle disease virus. It had been found that a large percentage of virus retains infectivity despite binding neutralizing antibody. This high persistent fraction of nonneutralized virus precluded the isolation of variants by the standard treatment with antibody alone. Rabbit anti-mouse immunoglobulin was used to reduce the percentage of virus that remains infectious despite the presence of bound antibody. This procedure made possible the isolation of variants of two distinct types: classical variants, not neutralized because they do not bind the antibody used to select them; and unique variants that, although still capable of binding the selecting antibody, are only slightly neutralized. The general applicability of this method for the isolation of antigenic variants in nonneutralizing epitopes is also discussed.
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Selected References
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- Ashe W. K., Notkins A. L. Neutralization of an infectious herpes simplex virus-antibody complex by anti-gamma-globulin. Proc Natl Acad Sci U S A. 1966 Aug;56(2):447–451. doi: 10.1073/pnas.56.2.447. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bratt M. A., Gallaher W. R. Preliminary analysis of the requirements for fusion from within and fusion from without by Newcastle disease virus. Proc Natl Acad Sci U S A. 1969 Oct;64(2):536–543. doi: 10.1073/pnas.64.2.536. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Caton A. J., Brownlee G. G., Yewdell J. W., Gerhard W. The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1 subtype). Cell. 1982 Dec;31(2 Pt 1):417–427. doi: 10.1016/0092-8674(82)90135-0. [DOI] [PubMed] [Google Scholar]
- Clavell L. A., Bratt M. A. Hemolytic interaction of Newcastle disease virus and chicken erythrocytes. II. Determining factors. Appl Microbiol. 1972 Mar;23(3):461–470. doi: 10.1128/am.23.3.461-470.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gerhard W., Webster R. G. Antigenic drift in influenza A viruses. I. Selection and characterization of antigenic variants of A/PR/8/34 (HON1) influenza virus with monoclonal antibodies. J Exp Med. 1978 Aug 1;148(2):383–392. doi: 10.1084/jem.148.2.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gerhard W., Yewdell J., Frankel M. E., Webster R. Antigenic structure of influenza virus haemagglutinin defined by hybridoma antibodies. Nature. 1981 Apr 23;290(5808):713–717. doi: 10.1038/290713a0. [DOI] [PubMed] [Google Scholar]
- Hightower L. E., Bratt M. A. Protein synthesis in Newcastle disease virus-infected chicken embryo cells. J Virol. 1974 Apr;13(4):788–800. doi: 10.1128/jvi.13.4.788-800.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Iorio R. M., Bratt M. A. Monoclonal antibodies as functional probes of the HN glycoprotein of Newcastle disease virus: antigenic separation of the hemagglutinating and neuraminidase sites. J Immunol. 1984 Oct;133(4):2215–2219. [PubMed] [Google Scholar]
- Iorio R. M., Bratt M. A. Monoclonal antibodies to newcastle disease virus: delineation of four epitopes on the HN glycoprotein. J Virol. 1983 Nov;48(2):440–450. doi: 10.1128/jvi.48.2.440-450.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Iorio R. M., Bratt M. A. Neutralization of Newcastle disease virus by monoclonal antibodies to the hemagglutinin-neuraminidase glycoprotein: requirement for antibodies to four sites for complete neutralization. J Virol. 1984 Aug;51(2):445–451. doi: 10.1128/jvi.51.2.445-451.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kingsford L. Enhanced neutralization of La Crosse virus by the binding of specific pairs of monoclonal antibodies to the G1 glycoprotein. Virology. 1984 Jul 30;136(2):265–273. doi: 10.1016/0042-6822(84)90163-6. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Laver W. G., Air G. M., Webster R. G., Gerhard W., Ward C. W., Dopheide T. A. Antigenic drift in type A influenza virus: sequence differences in the hemagglutinin of Hong Kong (H3N2) variants selected with monoclonal hybridoma antibodies. Virology. 1979 Oct 15;98(1):226–237. doi: 10.1016/0042-6822(79)90540-3. [DOI] [PubMed] [Google Scholar]
- Laver W. G., Gerhard W., Webster R. G., Frankel M. E., Air G. M. Antigenic drift in type A influenza virus: peptide mapping and antigenic analysis of A/PR/8/34 (HON1) variants selected with monoclonal antibodies. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1425–1429. doi: 10.1073/pnas.76.3.1425. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lefrancois L., Lyles D. S. Antigenic determinants of vesicular stomatitis virus: analysis with antigenic variants. J Immunol. 1983 Jan;130(1):394–398. [PubMed] [Google Scholar]
- Linscott W. D., Levinson W. E. Complement components required for virus neutralization by early immunoglobulin antibody. Proc Natl Acad Sci U S A. 1969 Oct;64(2):520–527. doi: 10.1073/pnas.64.2.520. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Majer M., Lik F. Sensitization of influenza virus A2-Singapore by antineuraminidase. J Gen Virol. 1971 Nov;13(2):355–356. doi: 10.1099/0022-1317-13-2-355. [DOI] [PubMed] [Google Scholar]
- Massey R. J., Schochetman G. Viral epitopes and monoclonal antibodies: isolation of blocking antibodies that inhibit virus neutralization. Science. 1981 Jul 24;213(4506):447–449. doi: 10.1126/science.6264601. [DOI] [PubMed] [Google Scholar]
- Nishikawa K., Isomura S., Suzuki S., Watanabe E., Hamaguchi M., Yoshida T., Nagai Y. Monoclonal antibodies to the HN glycoprotein of Newcastle disease virus. Biological characterization and use for strain comparisons. Virology. 1983 Oct 30;130(2):318–330. doi: 10.1016/0042-6822(83)90086-7. [DOI] [PubMed] [Google Scholar]
- Portner A. The HN glycoprotein of Sendai virus: analysis of site(s) involved in hemagglutinating and neuraminidase activities. Virology. 1981 Dec;115(2):375–384. doi: 10.1016/0042-6822(81)90118-5. [DOI] [PubMed] [Google Scholar]
- Portner A., Webster R. G., Bean W. J. Similar frequencies of antigenic variants in Sendai, vesicular stomatitis, and influenza A viruses. Virology. 1980 Jul 15;104(1):235–238. doi: 10.1016/0042-6822(80)90382-7. [DOI] [PubMed] [Google Scholar]
- Russell P. H., Griffiths P. C., Goswami K. K., Alexander D. J., Cannon M. J., Russell W. C. The characterization of monoclonal antibodies to Newcastle disease virus. J Gen Virol. 1983 Sep;64(Pt 9):2069–2072. doi: 10.1099/0022-1317-64-9-2069. [DOI] [PubMed] [Google Scholar]
- Russell P. H. Newcastle disease virus: the effect of monoclonal antibody in the overlay on virus penetration and the immunoselection of variants. J Gen Virol. 1984 Apr;65(Pt 4):795–798. doi: 10.1099/0022-1317-65-4-795. [DOI] [PubMed] [Google Scholar]
- Schmaljohn A. L., Johnson E. D., Dalrymple J. M., Cole G. A. Non-neutralizing monoclonal antibodies can prevent lethal alphavirus encephalitis. Nature. 1982 May 6;297(5861):70–72. doi: 10.1038/297070a0. [DOI] [PubMed] [Google Scholar]
- Stone M. R., Nowinski R. C. Topological mapping of murine leukemia virus proteins by competition-binding assays with monoclonal antibodies. Virology. 1980 Jan 30;100(2):370–381. doi: 10.1016/0042-6822(80)90528-0. [DOI] [PubMed] [Google Scholar]
- Webster R. G., Laver W. G., Air G. M., Ward C., Gerhard W., van Wyke K. L. The mechanism of antigenic drift in influenza viruses: analysis of Hong Kong (H3N2) variants with monoclonal antibodies to the hemagglutinin molecule. Ann N Y Acad Sci. 1980;354:142–161. doi: 10.1111/j.1749-6632.1980.tb27964.x. [DOI] [PubMed] [Google Scholar]
- Weiss S. R., Bratt M. A. Polyadenylate sequences on Newcastle disease virus mRNA synthesized in vivo and in vitro. J Virol. 1974 Jun;13(6):1220–1230. doi: 10.1128/jvi.13.6.1220-1230.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wiktor T. J., Koprowski H. Antigenic variants of rabies virus. J Exp Med. 1980 Jul 1;152(1):99–112. doi: 10.1084/jem.152.1.99. [DOI] [PMC free article] [PubMed] [Google Scholar]
- YOSHINO K., TANIGUCHI S. STUDIES ON THE NEUTRALIZATION OF HERPES SIMPLEX VIRUS. I. APPEARANCE OF NEUTRALIZING ANTIBODIES HAVING DIFFERENT GRADES OF COMPLEMENT REQUIREMENT. Virology. 1965 May;26:44–53. doi: 10.1016/0042-6822(65)90024-3. [DOI] [PubMed] [Google Scholar]
- Yewdell J., Gerhard W. Delineation of four antigenic sites on a paramyxovirus glycoprotein via which monoclonal antibodies mediate distinct antiviral activities. J Immunol. 1982 Jun;128(6):2670–2675. [PubMed] [Google Scholar]