1887

Abstract

The dengue virus (DENV) envelope protein domain 3 (ED3) is the target of potent virus neutralizing antibodies. The DENV-2 ED3 contains adjacent type-specific and DENV complex-reactive antigenic sites that are composed of a small number of residues that were previously demonstrated to be critical for antibody binding. Site-directed mutagenesis of a DENV-2 16681 infectious clone was used to mutate critical residues in the DENV-2 type-specific (K305A and P384A) and DENV complex-reactive (K310A) antigenic sites. The K305A mutant virus multiplied like the parent virus in mosquito and mammalian cells, as did the P384A mutant virus, which required a compensatory mutation (G330D) for viability. However, the K310A mutant virus could not be recovered. The DENV-2 type-specific critical residue mutations K305A and P384A+G330D reduced the ability of DENV-2 type-specific, but not DENV complex-reactive, mAbs to neutralize virus infectivity and this was directly correlated with mAb binding affinity to the rED3 mutants.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.070813-0
2015-02-01
2021-03-03
Loading full text...

Full text loading...

/deliver/fulltext/jgv/96/2/288.html?itemId=/content/journal/jgv/10.1099/vir.0.070813-0&mimeType=html&fmt=ahah

References

  1. Chambers T. J., Hahn C. S., Galler R., Rice C. M. 1990; Flavivirus genome organization, expression, and replication. Annu Rev Microbiol 44:649–688 [CrossRef][PubMed]
    [Google Scholar]
  2. Chen Y., Maguire T., Hileman R. E., Fromm J. R., Esko J. D., Linhardt R. J., Marks R. M. 1997; Dengue virus infectivity depends on envelope protein binding to target cell heparan sulfate. Nat Med 3:866–871 [CrossRef][PubMed]
    [Google Scholar]
  3. Cockburn J. J., Navarro Sanchez M. E., Fretes N., Urvoas A., Staropoli I., Kikuti C. M., Coffey L. L., Arenzana Seisdedos F., Bedouelle H., Rey F. A. 2012; Mechanism of dengue virus broad cross-neutralization by a monoclonal antibody. Structure 20:303–314 [CrossRef][PubMed]
    [Google Scholar]
  4. Erb S. M., Butrapet S., Moss K. J., Luy B. E., Childers T., Calvert A. E., Silengo S. J., Roehrig J. T., Huang C. Y., Blair C. D. 2010; Domain-III FG loop of the dengue virus type 2 envelope protein is important for infection of mammalian cells and Aedes aegypti mosquitoes. Virology 406:328–335 [CrossRef][PubMed]
    [Google Scholar]
  5. Fibriansah G., Tan J. L., Smith S. A., de Alwis A. R., Ng T. S., Kostyuchenko V. A., Ibarra K. D., Wang J., Harris E. et al. 2014; A potent anti-dengue human antibody preferentially recognizes the conformation of E protein monomers assembled on the virus surface. EMBO Mol Med 6:358–371 [CrossRef][PubMed]
    [Google Scholar]
  6. Gromowski G. D., Barrett A. D. 2007; Characterization of an antigenic site that contains a dominant, type-specific neutralization determinant on the envelope protein domain III (ED3) of dengue 2 virus. Virology 366:349–360 [CrossRef][PubMed]
    [Google Scholar]
  7. Gromowski G. D., Barrett N. D., Barrett A. D. 2008; Characterization of dengue virus complex-specific neutralizing epitopes on envelope protein domain III of dengue 2 virus. J Virol 82:8828–8837 [CrossRef][PubMed]
    [Google Scholar]
  8. Gromowski G. D., Roehrig J. T., Diamond M. S., Lee J. C., Pitcher T. J., Barrett A. D. 2010; Mutations of an antibody binding energy hot spot on domain III of the dengue 2 envelope glycoprotein exploited for neutralization escape. Virology 407:237–246 [CrossRef][PubMed]
    [Google Scholar]
  9. Hiramatsu K., Tadano M., Men R., Lai C. J. 1996; Mutational analysis of a neutralization epitope on the dengue type 2 virus (DEN2) envelope protein: monoclonal antibody resistant DEN2/DEN4 chimeras exhibit reduced mouse neurovirulence. Virology 224:437–445 [CrossRef][PubMed]
    [Google Scholar]
  10. Huang C. Y., Butrapet S., Moss K. J., Childers T., Erb S. M., Calvert A. E., Silengo S. J., Kinney R. M., Blair C. D., Roehrig J. T. 2010; The dengue virus type 2 envelope protein fusion peptide is essential for membrane fusion. Virology 396:305–315 [CrossRef][PubMed]
    [Google Scholar]
  11. Hung J. J., Hsieh M. T., Young M. J., Kao C. L., King C. C., Chang W. 2004; An external loop region of domain III of dengue virus type 2 envelope protein is involved in serotype-specific binding to mosquito but not mammalian cells. J Virol 78:378–388 [CrossRef][PubMed]
    [Google Scholar]
  12. Kinney R. M., Butrapet S., Chang G. J., Tsuchiya K. R., Roehrig J. T., Bhamarapravati N., Gubler D. J. 1997; Construction of infectious cDNA clones for dengue 2 virus: strain 16681 and its attenuated vaccine derivative, strain PDK-53. Virology 230:300–308 [CrossRef][PubMed]
    [Google Scholar]
  13. Kuhn R. J., Zhang W., Rossmann M. G., Pletnev S. V., Corver J., Lenches E., Jones C. T., Mukhopadhyay S., Chipman P. R., Strauss E. G. 2002; Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Cell 108:717–725 [CrossRef][PubMed]
    [Google Scholar]
  14. Modis Y., Ogata S., Clements D., Harrison S. C. 2003; A ligand-binding pocket in the dengue virus envelope glycoprotein. Proc Natl Acad Sci U S A 100:6986–6991 [CrossRef][PubMed]
    [Google Scholar]
  15. Pierson T. C., Diamond M. S. 2008; Molecular mechanisms of antibody-mediated neutralisation of flavivirus infection. Expert Rev Mol Med 10:e12 [CrossRef][PubMed]
    [Google Scholar]
  16. Pierson T. C., Fremont D. H., Kuhn R. J., Diamond M. S. 2008; Structural insights into the mechanisms of antibody-mediated neutralization of flavivirus infection: implications for vaccine development. Cell Host Microbe 4:229–238 [CrossRef][PubMed]
    [Google Scholar]
  17. Pitcher T. J., Gromowski G. D., Beasley D. W., Barrett A. D. 2012; Conservation of the DENV-2 type-specific and DEN complex-reactive antigenic sites among DENV-2 genotypes. Virology 422:386–392 [CrossRef][PubMed]
    [Google Scholar]
  18. Roehrig J. T., Bolin R. A., Kelly R. G. 1998; Monoclonal antibody mapping of the envelope glycoprotein of the dengue 2 virus, Jamaica. Virology 246:317–328 [CrossRef][PubMed]
    [Google Scholar]
  19. Roehrig J. T., Butrapet S., Liss N. M., Bennett S. L., Luy B. E., Childers T., Boroughs K. L., Stovall J. L., Calvert A. E. et al. 2013; Mutation of the dengue virus type 2 envelope protein heparan sulfate binding sites or the domain III lateral ridge blocks replication in Vero cells prior to membrane fusion. Virology 441:114–125 [CrossRef][PubMed]
    [Google Scholar]
  20. Smith S. A., de Alwis R., Kose N., Durbin A. P., Whitehead S. S., de Silva A. M., Crowe J. E. Jr 2013; Human monoclonal antibodies derived from memory B cells following live attenuated dengue virus vaccination or natural infection exhibit similar characteristics. J Infect Dis 207:1898–1908 [CrossRef][PubMed]
    [Google Scholar]
  21. Sukupolvi-Petty S., Austin S. K., Purtha W. E., Oliphant T., Nybakken G. E., Schlesinger J. J., Roehrig J. T., Gromowski G. D., Barrett A. D. et al. 2007; Type- and subcomplex-specific neutralizing antibodies against domain III of dengue virus type 2 envelope protein recognize adjacent epitopes. J Virol 81:12816–12826 [CrossRef][PubMed]
    [Google Scholar]
  22. Sukupolvi-Petty S., Austin S. K., Engle M., Brien J. D., Dowd K. A., Williams K. L., Johnson S., Rico-Hesse R., Harris E. et al. 2010; Structure and function analysis of therapeutic monoclonal antibodies against dengue virus type 2. J Virol 84:9227–9239 [CrossRef][PubMed]
    [Google Scholar]
  23. Wahala W. M., Huang C., Butrapet S., White L. J., de Silva A. M. 2012; Recombinant dengue type 2 viruses with altered e protein domain III epitopes are efficiently neutralized by human immune sera. J Virol 86:4019–4023 [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.070813-0
Loading
/content/journal/jgv/10.1099/vir.0.070813-0
Loading

Data & Media loading...

Supplements

Supplementary Data

PDF

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error