Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1995 Mar;69(3):1990–1993. doi: 10.1128/jvi.69.3.1990-1993.1995

Roles of immunoglobulin valency and the heavy-chain constant domain in antibody-mediated downregulation of Sindbis virus replication in persistently infected neurons.

S Ubol 1, B Levine 1, S H Lee 1, N S Greenspan 1, D E Griffin 1
PMCID: PMC188823  PMID: 7853547

Abstract

Clearance of infectious Sindbis virus from neurons is mediated by antibody to the E2 glycoprotein. Properties of the antibody important for downregulation of Sindbis virus replication are unknown. Immunoglobulin isotypes and valency determine many biological properties of antibodies. An immunoglobulin G1 (IgG1) isotype switch mutant and F(ab')2 and Fab fragments of IgG3 monoclonal antibody 209 were prepared and tested for clearance of infectious virus from persistently infected rat dorsal root ganglion neurons in vitro. IgG1, IgG3, and IgG3-derived F(ab')2 fragments were similarly efficacious, while IgG3-derived Fab fragments had no effect on virus replication. Cross-linking of Fab with secondary antibodies restored antiviral activity. Therefore, we found no evidence that IgG subclass plays a role in control of intracellular Sindbis virus replication. However, bivalency appears to be crucial for the ability of E2-specific IgG molecules to mediate clearance of infectious virus from neuron cells, suggesting that cross-linking of E2 molecules is essential.

Full Text

The Full Text of this article is available as a PDF (164.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amano T., Richelson E., Nirenberg M. Neurotransmitter synthesis by neuroblastoma clones (neuroblast differentiation-cell culture-choline acetyltransferase-acetylcholinesterase-tyrosine hydroxylase-axons-dendrites). Proc Natl Acad Sci U S A. 1972 Jan;69(1):258–263. doi: 10.1073/pnas.69.1.258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cooper L. J., Schimenti J. C., Glass D. D., Greenspan N. S. H chain C domains influence the strength of binding of IgG for streptococcal group A carbohydrate. J Immunol. 1991 Apr 15;146(8):2659–2663. [PubMed] [Google Scholar]
  3. Coutelier J. P., van der Logt J. T., Heessen F. W., Warnier G., Van Snick J. IgG2a restriction of murine antibodies elicited by viral infections. J Exp Med. 1987 Jan 1;165(1):64–69. doi: 10.1084/jem.165.1.64. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dalrymple J. M., Schlesinger S., Russell P. K. Antigenic characterization of two sindbis envelope glycoproteins separated by isoelectric focusing. Virology. 1976 Jan;69(1):93–103. doi: 10.1016/0042-6822(76)90197-5. [DOI] [PubMed] [Google Scholar]
  5. Erlendsson K., Swartz T., Dwyer J. M. Successful reversal of echovirus encephalitis in X-linked hypogammaglobulinemia by intraventricular administration of immunoglobulin. N Engl J Med. 1985 Feb 7;312(6):351–353. doi: 10.1056/NEJM198502073120605. [DOI] [PubMed] [Google Scholar]
  6. Hunt A. R., Short W. A., Johnson A. J., Bolin R. A., Roehrig J. T. Synthetic peptides of the E2 glycoprotein of Venezuelan equine encephalomyelitis virus. II. Antibody to the amino terminus protects animals by limiting viral replication. Virology. 1991 Nov;185(1):281–290. doi: 10.1016/0042-6822(91)90775-7. [DOI] [PubMed] [Google Scholar]
  7. Jackson A. C., Moench T. R., Trapp B. D., Griffin D. E. Basis of neurovirulence in Sindbis virus encephalomyelitis of mice. Lab Invest. 1988 May;58(5):503–509. [PubMed] [Google Scholar]
  8. Johnson R. T., McFarland H. F., Levy S. E. Age-dependent resistance to viral encephalitis: studies of infections due to Sindbis virus in mice. J Infect Dis. 1972 Mar;125(3):257–262. doi: 10.1093/infdis/125.3.257. [DOI] [PubMed] [Google Scholar]
  9. Levine B., Griffin D. E. Persistence of viral RNA in mouse brains after recovery from acute alphavirus encephalitis. J Virol. 1992 Nov;66(11):6429–6435. doi: 10.1128/jvi.66.11.6429-6435.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Levine B., Hardwick J. M., Trapp B. D., Crawford T. O., Bollinger R. C., Griffin D. E. Antibody-mediated clearance of alphavirus infection from neurons. Science. 1991 Nov 8;254(5033):856–860. doi: 10.1126/science.1658936. [DOI] [PubMed] [Google Scholar]
  11. Levine B., Huang Q., Isaacs J. T., Reed J. C., Griffin D. E., Hardwick J. M. Conversion of lytic to persistent alphavirus infection by the bcl-2 cellular oncogene. Nature. 1993 Feb 25;361(6414):739–742. doi: 10.1038/361739a0. [DOI] [PubMed] [Google Scholar]
  12. Lustig S., Jackson A. C., Hahn C. S., Griffin D. E., Strauss E. G., Strauss J. H. Molecular basis of Sindbis virus neurovirulence in mice. J Virol. 1988 Jul;62(7):2329–2336. doi: 10.1128/jvi.62.7.2329-2336.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mease P. J., Ochs H. D., Wedgwood R. J. Successful treatment of echovirus meningoencephalitis and myositis-fasciitis with intravenous immune globulin therapy in a patient with X-linked agammaglobulinemia. N Engl J Med. 1981 May 21;304(21):1278–1281. doi: 10.1056/NEJM198105213042107. [DOI] [PubMed] [Google Scholar]
  14. Mendoza Q. P., Stanley J., Griffin D. E. Monoclonal antibodies to the E1 and E2 glycoproteins of Sindbis virus: definition of epitopes and efficiency of protection from fatal encephalitis. J Gen Virol. 1988 Dec;69(Pt 12):3015–3022. doi: 10.1099/0022-1317-69-12-3015. [DOI] [PubMed] [Google Scholar]
  15. Müller C. E., Rajewsky K. Isolation of immunoglobulin class switch variants from hybridoma lines secreting anti-idiotope antibodies by sequential sublining. J Immunol. 1983 Aug;131(2):877–881. [PubMed] [Google Scholar]
  16. Nguyen L., Knipe D. M., Finberg R. W. Mechanism of virus-induced Ig subclass shifts. J Immunol. 1994 Jan 15;152(2):478–484. [PubMed] [Google Scholar]
  17. Schreiber J. R., Cooper L. J., Diehn S., Dahlhauser P. A., Tosi M. F., Glass D. D., Patawaran M., Greenspan N. S. Variable region-identical monoclonal antibodies of different IgG subclass directed to Pseudomonas aeruginosa lipopolysaccharide O-specific side chain function differently. J Infect Dis. 1993 Jan;167(1):221–226. doi: 10.1093/infdis/167.1.221. [DOI] [PubMed] [Google Scholar]
  18. Stanley J., Cooper S. J., Griffin D. E. Alphavirus neurovirulence: monoclonal antibodies discriminating wild-type from neuroadapted Sindbis virus. J Virol. 1985 Oct;56(1):110–119. doi: 10.1128/jvi.56.1.110-119.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Stanley J., Cooper S. J., Griffin D. E. Monoclonal antibody cure and prophylaxis of lethal Sindbis virus encephalitis in mice. J Virol. 1986 Apr;58(1):107–115. doi: 10.1128/jvi.58.1.107-115.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Tyor W. R., Moench T. R., Griffin D. E. Characterization of the local and systemic B cell response of normal and athymic nude mice with Sindbis virus encephalitis. J Neuroimmunol. 1989 Oct;24(3):207–215. doi: 10.1016/0165-5728(89)90118-5. [DOI] [PubMed] [Google Scholar]
  21. Tyor W. R., Wesselingh S., Levine B., Griffin D. E. Long term intraparenchymal Ig secretion after acute viral encephalitis in mice. J Immunol. 1992 Dec 15;149(12):4016–4020. [PubMed] [Google Scholar]
  22. Wahlberg J. M., Bron R., Wilschut J., Garoff H. Membrane fusion of Semliki Forest virus involves homotrimers of the fusion protein. J Virol. 1992 Dec;66(12):7309–7318. doi: 10.1128/jvi.66.12.7309-7318.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wesselingh S. L., Levine B., Fox R. J., Choi S., Griffin D. E. Intracerebral cytokine mRNA expression during fatal and nonfatal alphavirus encephalitis suggests a predominant type 2 T cell response. J Immunol. 1994 Feb 1;152(3):1289–1297. [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES