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. 1992;123(1):89–100. doi: 10.1007/BF01317140

Mode of neutralization of lactate dehydrogenase-elevating virus by polyclonal and monoclonal antibodies

P G W Plagemann 1, J T Harty 1, C Even 1
PMCID: PMC7087216  PMID: 1372497

Summary

Neutralization of the infectivity of [3H]uridine-labeled lactate dehydrogenase-elevating virus (LDV) by polyclonal mouse or rabbit antibodies to the envelope glycoprotein of LDV, VP-3, or by neutralizing monoclonal antibodies (mAb) that recognize a different epitope on VP-3 than the polyclonal antibodies correlated with an increase in the sedimentation rate of LDV from 230 S to ≧270 S. Incubation of LDV with normal mouse plasma or nonneutralizing mAbs to LDV VP-3 had no effect on its sedimentation rate. Similarly, incubation of a neutralization escape variant of LDV with the mAb used in its selection had no effect on its sedimentation rate, whereas neutralization of this variant by polyclonal mouse or rabbit anti-VP 3 antibodies increased the sedimentation rate. Neutralization of LDV infectivity was only observed at high antibody/virion ratios and often was followed by loss of the viral RNA. The results suggest that neutralization of LDV infectivity results from binding of multiple antibody molecules that recognize specific epitopes on the viral envelope glycoprotein and ultimately leads to disintegration of the virions.

Keywords: Lactate, Monoclonal Antibody, Infectious Disease, Sedimentation Rate, Polyclonal Antibody

References

  • 1.Brinton-Darnell M, Plagemann PGW. Structure and chemical-physical characteristics of lactate dehydrogenase-elevating virus and its RNA. J Virol. 1975;16:420–433. doi: 10.1128/jvi.16.2.420-433.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Buxton IK, Chan SPK, Plagemann PGW. The IA antigen is not the major receptor for lactate dehydrogenase-elevating virus on macrophages from CBA and BALB/c mice. Virus Res. 1988;9:205–219. doi: 10.1016/0168-1702(88)90031-7. [DOI] [PubMed] [Google Scholar]
  • 3.Cafruny WA, Chan SPK, Harty JT, Yousefi S, Kowalchyk K, McDonald D, Foreman B, Budweg G, Plagemann PGW. Antibody response of mice to lactate dehydrogenase-elevating virus during infection and immunization with inactivated virus. Virus Res. 1986;5:357–375. doi: 10.1016/0168-1702(86)90029-8. [DOI] [PubMed] [Google Scholar]
  • 4.Cafruny WA, Plagemann PGW. Immune response to lactate dehydrogenase-elevating virus: serologically specific rabbit neutralizing antibody to the virus. Infect Immun. 1982;37:1007–1012. doi: 10.1128/iai.37.3.1007-1012.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Colonno RJ, Callahan PL, Leippe DM, Rueckert RR, Tomassini J. Inhibition of rhinovirus attachment by neutralizing monoclonal antibodies and their Fab fragments. J Virol. 1989;63:36–42. doi: 10.1128/jvi.63.1.36-42.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Contag CH, Harty JT, Plagemann PGW. Dual virus aetiology of age-dependent poliomyelitis of mice. A potential model for human motor neuron diseases. Microb Pathog. 1989;6:391–401. doi: 10.1016/0882-4010(89)90081-8. [DOI] [PubMed] [Google Scholar]
  • 7.Cooper NR. Humoral immunity to viruses. Compr Virol. 1979;15:123–170. [Google Scholar]
  • 8.Dietschold B, Tollis M, Lafon M, Wunner M, Koprowski H. Mechanisms of rabies virus neutralization by glycoprotein-specific monoclonal antibodies. Virology. 1987;161:29–36. doi: 10.1016/0042-6822(87)90167-x. [DOI] [PubMed] [Google Scholar]
  • 9.Godeny EK, Speicher DW, Brinton MA. Map location of lactate dehydrogenase-elevating virus (LDV) capsid protein (Vp 1) gene. Virology. 1990;177:768–771. doi: 10.1016/0042-6822(90)90546-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Gollins SW, Porterfield JS. A new mechanism for neutralization of enveloped viruses by antiviral antibodies. Nature. 1986;321:244–246. doi: 10.1038/321244a0. [DOI] [PubMed] [Google Scholar]
  • 11.Harty JT, Chan SPK, Plagemann PGW. Characteristics of monoclonal antibodies to the lactate dehydrogenase-elevating virus. Intervirology. 1987;27:53–60. doi: 10.1159/000149715. [DOI] [PubMed] [Google Scholar]
  • 12.Harty JT, Plagemann PGW. Formalin inactivation of the lactate dehydrogenase-elevating virus reveals a major neutralizing epitope not recognized during natural infection. J Virol. 1988;62:3210–3216. doi: 10.1128/jvi.62.9.3210-3216.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Harty JT, Plagemann PGW. Monoclonal antibody protection from age-dependent poliomyelitis: Implications regarding pathogenesis of lactate dehydrogenase-elevating virus. J Virol. 1990;64:6257–6262. doi: 10.1128/jvi.64.12.6257-6262.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Horzinek MC. The structure of togaviruses. Prog Med Virol. 1973;16:101–156. [PubMed] [Google Scholar]
  • 15.Horzinek MC, van Wielink PS, Ellens DJ. Purification and electron microscopy of lactic dehydrogenase virus of mice. J Gen Virol. 1975;26:217–226. doi: 10.1099/0022-1317-26-3-217. [DOI] [PubMed] [Google Scholar]
  • 16.Inada T, Mims CA. Ia antigens and Fc receptors of mouse peritoneal macrophages as determinants of susceptibility to lactic dehydrogenase virus. J Gen Virol. 1985;66:1469–1477. doi: 10.1099/0022-1317-66-7-1469. [DOI] [PubMed] [Google Scholar]
  • 17.Iorio RM. Mechanisms of neutralization of animal viruses. Monoclonal antibodies provide a new prospective. Microb Pathog. 1988;5:1–7. doi: 10.1016/0882-4010(88)90075-7. [DOI] [PubMed] [Google Scholar]
  • 18.Kowalchyk K, Plagemann PGW. Cell surface receptors for lactate dehydrogenase-elevating virus on subpopulation of macrophages. Virus Res. 1985;2:211–229. doi: 10.1016/0168-1702(85)90010-3. [DOI] [PubMed] [Google Scholar]
  • 19.Kuo L, Harty JT, Erickson L, Palmer GA, Plagemann PGW. A nested set of eight RNAs is formed in macrophages infected with lactate dehydrogenase-elevating virus. J Virol. 1991;65:5118–5123. doi: 10.1128/jvi.65.9.5118-5123.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Lachmann PJ. Antibody and complement in viral infections. Br Med Bull. 1985;41:3–6. doi: 10.1093/oxfordjournals.bmb.a072020. [DOI] [PubMed] [Google Scholar]
  • 21.Mandel B. Interactions of viruses with neutralizing antibodies. Compr Virol. 1979;15:37–121. [Google Scholar]
  • 22.Norrby E. Immunogenicity of vaccine products and neutralizing antibodies. In: Notkins A, Oldstone MBA, editors. Concepts in viral pathogenesis, vol II. New York: Springer; 1986. pp. 346–353. [Google Scholar]
  • 23.Mosser AG, Leippe DM, Rueckert RR. Neutralization of picornaviruses: support for the pentamer bridging hypothesis. In: Semler BL, Ehrenfield E, editors. Molecular aspects of picornavirus infection and detection. Washington: American Society of Microbiology; 1989. pp. 155–167. [Google Scholar]
  • 24.Oldstone MBA, Buchmeyer JJ, Doyle MV, Tishon A. Virus-induced immune complex disease: specific antiviral antibody and Clq binding material in the circulation during persistent lymphocytic choriomeningitis virus infection. J Immunol. 1980;124:831–838. [PubMed] [Google Scholar]
  • 25.Onyekaba CO, Harty JT, Even C, Hu B, Plagemann PGW. Persistent infection of mice by lactate dehydrogenase-elevating virus: effects of immunosuppression on virus replication and antiviral immune responses. Virus Res. 1989;14:297–316. doi: 10.1016/0168-1702(89)90023-3. [DOI] [PubMed] [Google Scholar]
  • 26.Onyekaba CO, Harty JT, Plagemann PGW. Extensive cytocidal replication of lactate dehydrogenase-elevating virus in cultured peritoneal macrophages from 1–2 week old mice. Virus Res. 1989;14:327–338. doi: 10.1016/0168-1702(89)90025-7. [DOI] [PubMed] [Google Scholar]
  • 27.Outlaw MC, Armstrong SJ, Dinnock NJ. Mechanisms of neutralization of influenza virus in tracheal epithelial and BHK cells vary according to IgG concentration. Virology. 1990;178:478–485. doi: 10.1016/0042-6822(90)90345-r. [DOI] [PubMed] [Google Scholar]
  • 28.Plagemann PGW, Gregory KF, Swim HE, Chan KKW. Plasma lactate dehydrogenase-elevating agent of mice: distribution in tissues and effect on lactate dehydrogenase isozyme patterns. Can J Microb. 1963;9:75–86. [Google Scholar]
  • 29.Plagemann PGW, Moennig V (1991) Lactate dehydrogenase-elevating virus, equine arteritis virus and simian haemorrhagic fever virus. Adv Virus Res (in press) [DOI] [PMC free article] [PubMed]
  • 30.Roehrig JT, Hunt AR, Kinney RM, Mathews JH. In vitro mechanism of monoclonal antibody neutralization of alphaviruses. Virology. 1988;165:66–73. doi: 10.1016/0042-6822(88)90659-9. [DOI] [PubMed] [Google Scholar]
  • 31.Rowson KEK, Mahy BWJ. Lactic dehydrogenase virus. In: Kingsbury DW, Zur Hausen H, editors. Virology monographs, vol 13. Wien New York: Springer; 1975. [DOI] [PubMed] [Google Scholar]
  • 32.Rowson KEK, Mahy BWJ. Lactate dehydrogenase-elevating virus. J Gen Virol. 1985;66:2297–2312. doi: 10.1099/0022-1317-66-11-2297. [DOI] [PubMed] [Google Scholar]
  • 33.Stueckemann JA, Ritzi DM, Holth M, Smith MS, Swart WJ, Cafruny WA, Plagemann PGW. Replication of lactate dehydrogenase-elevating virus in macrophages. I. Evidence for cytocidal replication. J Gen Virol. 1982;59:245–262. doi: 10.1099/0022-1317-59-2-245. [DOI] [PubMed] [Google Scholar]
  • 34.Stueckemann JA, Holth M, Swart WJ, Kowalchyk K, Smith MS, Wolstenholme AJ, Cafruny WA, Plagemann PGW. Replication of lactate dehydrogenase-elevating virus in macrophages. II. Mechanism of persistent infection in mice and cell culture. J Gen Virol. 1982;59:263–272. doi: 10.1099/0022-1317-59-2-263. [DOI] [PubMed] [Google Scholar]
  • 35.Thomas AAM, Vrijsen R, Boeye A. Relationship between poliovirus neutralization and aggregation. J Virol. 1986;59:479–485. doi: 10.1128/jvi.59.2.479-485.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Tong SL, Stueckemann JA, Plagemann PGW. Autoradiographic method for detection of lactate dehydrogenase-elevating virus-infected cells in primary macrophage cultures. J Virol. 1977;22:219–227. doi: 10.1128/jvi.22.1.219-227.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Tooker P, Kennedy SIT. Semliki Forest virus multiplication in clones ofAedes albipictus cells. J Virol. 1981;37:589–600. doi: 10.1128/jvi.37.2.589-600.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Westaway FG, Brinton MA, Gaidamovich SY, Horzinek MC, Igarashi A, Kaariainen L, Lvov DK, Porterfield JS, Russel PK, Trent DW. Togaviridae. Intervirology. 1985;24:125–139. doi: 10.1159/000149632. [DOI] [PubMed] [Google Scholar]
  • 39.Wohlfahrt C. Neutralization of adenoviruses: kinetics, stochiometry and mechanisms. J Virol. 1988;62:2321–2328. doi: 10.1128/jvi.62.7.2321-2328.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]

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