Skip to main content

Advertisement

Log in

The effect of human immunodeficiency virus type 1 (HIV-1) gp41 variability on antibody detection

  • Original Article
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

To determine whether genetic variability influences the ability to detect antibody, nine gp41 ectodomain recombinant proteins from human immunodeficiency virus type 1 (HIV-1) CRF07_BC, CRF01_AE and subtype B′ were expressed in a bacterial expression system and purified. An indirect sandwich ELISA was developed with individual purified recombinant proteins. Plasma samples from 26 individuals infected with HIV-1 of different subtypes and four samples from the 1st international antibody reference panel were tested against each recombinant protein by ELISA. Heat-map and two-dimensional hierarchical clustering methods revealed that ELISA reactivity against antigens derived from the same subtypes clustered together. This suggests a similar reactivity pattern among infections of the same subtype, and thus the antigenicity of gp41 recombinant proteins may vary depending on the subtype, and subtype-related serotypes may exist among these antigens. Using association analysis methods, eight signature sites related to the subtype-specific reactivity patterns were identified. This study provides valuable information for the development of diagnostic assays with the ability to detect broadly cross-reactive antibodies induced by infection with different HIV-1 subtypes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Bhattacharya T, Daniels M, Heckerman D, Foley B, Frahm N, Kadie C, Carlson J, Yusim K, McMahon B, Gaschen B, Mallal S, Mullins JI, Nickle DC, Herbeck J, Rousseau C, Learn GH, Miura T, Brander C, Walker B, Korber B (2007) Founder effects in the assessment of HIV polymorphisms and HLA allele associations. Science 315:1583–1586

    Article  CAS  PubMed  Google Scholar 

  2. Binley JM, Klasse PJ, Cao Y, Jones I, Markowitz M, Ho DD, Moore JP (1997) Differential regulation of the antibody responses to Gag and Env proteins of human immunodeficiency virus type 1. J Virol 71:2799–2809

    CAS  PubMed  Google Scholar 

  3. Binley JM, Wrin T, Korber B, Zwick MB, Wang M, Chappey C, Stiegler G, Kunert R, Zolla-Pazner S, Katinger H, Petropoulos CJ, Burton DR (2004) Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies. J Virol 78:13232–13252

    Article  CAS  PubMed  Google Scholar 

  4. Buchacher A, Predl R, Strutzenberger K, Steinfellner W, Trkola A, Purtscher M, Gruber G, Tauer C, Steindl F, Jungbauer A (1994) Generation of human monoclonal antibodies against HIV-1 proteins; electrofusion and Epstein-Barr virus transformation for peripheral blood lymphocyte immortalization. AIDS Res Hum Retroviruses 10:359–369

    Article  CAS  PubMed  Google Scholar 

  5. Busch MP, Lee LL, Satten GA, Henrard DR, Farzadegan H, Nelson KE, Read S, Dodd RY, Petersen LR (1995) Time course of detection of viral and serologic markers preceding human immunodeficiency virus type 1 seroconversion: implications for screening of blood and tissue donors. Transfusion 35:91–97

    Article  CAS  PubMed  Google Scholar 

  6. Butler IF, Pandrea I, Marx PA, Apetrei C (2007) HIV genetic diversity: biological and public health consequences. Curr HIV Res 5:23–45

    Article  CAS  PubMed  Google Scholar 

  7. Chan DC, Fass D, Berger JM, Kim PS (1997) Core structure of gp41 from the HIV envelope glycoprotein. Cell 89:263–273

    Article  CAS  PubMed  Google Scholar 

  8. Chong H, Hong K, Zhang C, Nie J, Song A, Kong W, Wang Y (2008) Genetic and neutralization properties of HIV-1 env clones from subtype B/BC/AE infections in China. J Acquir Immune Defic Syndr 47:535–543

    Article  CAS  PubMed  Google Scholar 

  9. Dean CB, Nielsen JD (2007) Generalized linear mixed models: a review and some extensions. Lifetime Data Anal 13:497–512

    Article  CAS  PubMed  Google Scholar 

  10. Derby NR, Gray S, Wayner E, Campogan D, Vlahogiannis G, Kraft Z, Barnett SW, Srivastava IK, Stamatatos L (2007) Isolation and characterization of monoclonal antibodies elicited by trimeric HIV-1 Env gp140 protein immunogens. Virology 366:433–445

    Article  CAS  PubMed  Google Scholar 

  11. Dorn J, Masciotra S, Yang C, Downing R, Biryahwaho B, Mastro TD, Nkengasong J, Pieniazek D, Rayfield MA, Hu DJ, Lal RB (2000) Analysis of genetic variability within the immunodominant epitopes of envelope gp41 from human immunodeficiency virus type 1 (HIV-1) group M and its impact on HIV-1 antibody detection. J Clin Microbiol 38:773–780

    CAS  PubMed  Google Scholar 

  12. Eddleston M, de La Torre JC, Xu JY, Dorfman N, Notkins A, Zolla-Pazner S, Oldstone MB (1993) Molecular mimicry accompanying HIV-1 infection: human monoclonal antibodies that bind to gp41 and to astrocytes. AIDS Res Hum Retroviruses 9:939–944

    Article  CAS  PubMed  Google Scholar 

  13. Ellenberger DL, Sullivan PS, Dorn J, Schable C, Spira TJ, Folks TM, Lal RB (1999) Viral and immunologic examination of human immunodeficiency virus type 1-infected, persistently seronegative persons. J Infect Dis 180:1033–1042

    Article  CAS  PubMed  Google Scholar 

  14. Fiebig EW, Wright DJ, Rawal BD, Garrett PE, Schumacher RT, Peddada L, Heldebrant C, Smith R, Conrad A, Kleinman SH, Busch MP (2003) Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection. AIDS 17:1871–1879

    Article  PubMed  Google Scholar 

  15. Gnann JW Jr, Nelson JA, Oldstone MB (1987) Fine mapping of an immunodominant domain in the transmembrane glycoprotein of human immunodeficiency virus. J Virol 61:2639–2641

    CAS  PubMed  Google Scholar 

  16. Gnann JW Jr, Schwimmbeck PL, Nelson JA, Truax AB, Oldstone MB (1987) Diagnosis of AIDS by using a 12-amino acid peptide representing an immunodominant epitope of the human immunodeficiency virus. J Infect Dis 156:261–267

    CAS  PubMed  Google Scholar 

  17. Gorny MK, Zolla-Pazner S (2000) Recognition by human monoclonal antibodies of free and complexed peptides representing the prefusogenic and fusogenic forms of human immunodeficiency virus type 1 gp41. J Virol 74:6186–6192

    Article  CAS  PubMed  Google Scholar 

  18. Hemelaar J, Gouws E, Ghys PD, Osmanov S (2006) Global and regional distribution of HIV-1 genetic subtypes and recombinants in 2004. AIDS 20:W13–W23

    Article  PubMed  Google Scholar 

  19. Holguin A, Lopez M, Molinero M, Soriano V (2008) Performance of three commercial viral load assays, Versant human immunodeficiency virus type 1 (HIV-1) RNA bDNA v3.0, Cobas AmpliPrep/Cobas TaqMan HIV-1, and NucliSens HIV-1 EasyQ v1.2, testing HIV-1 non-B subtypes and recombinant variants. J Clin Microbiol 46:2918–2923

    Article  CAS  PubMed  Google Scholar 

  20. Horal P, Svennerholm B, Jeansson S, Rymo L, Hall WW, Vahlne A (1991) Continuous epitopes of the human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein and reactivity of human sera to synthetic peptides representing various HIV-1 isolates. J Virol 65:2718–2723

    CAS  PubMed  Google Scholar 

  21. Legastelois I, Desgranges C (2000) Design and intracellular activity of a human single-chain antibody to human immunodeficiency virus type 1 conserved gp41 epitope. J Virol 74:5712–5715

    Article  CAS  PubMed  Google Scholar 

  22. Muster T, Steindl F, Purtscher M, Trkola A, Klima A, Himmler G, Ruker F, Katinger H (1993) A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J Virol 67:6642–6647

    CAS  PubMed  Google Scholar 

  23. Ofek G, Tang M, Sambor A, Katinger H, Mascola JR, Wyatt R, Kwong PD (2004) Structure and mechanistic analysis of the anti-human immunodeficiency virus type 1 antibody 2F5 in complex with its gp41 epitope. J Virol 78:10724–10737

    Article  CAS  PubMed  Google Scholar 

  24. Sattentau QJ, Zolla-Pazner S, Poignard P (1995) Epitope exposure on functional, oligomeric HIV-1 gp41 molecules. Virology 206:713–717

    Article  CAS  PubMed  Google Scholar 

  25. Triques K, Coste J, Perret JL, Segarra C, Mpoudi E, Reynes J, Delaporte E, Butcher A, Dreyer K, Herman S, Spadoro J, Peeters M (1999) Efficiencies of four versions of the AMPLICOR HIV-1 MONITOR test for quantification of different subtypes of human immunodeficiency virus type 1. J Clin Microbiol 37:110–116

    CAS  PubMed  Google Scholar 

  26. Wang Y, Song A, Xu S, Li X, Chong H, Zhao C, Nie J, Zhang C (2008) Impact of HIV-1 genetic diversity in China on the measurement of viral load. J Med Virol 80:1–8

    Article  CAS  PubMed  Google Scholar 

  27. Xu JY, Gorny MK, Palker T, Karwowska S, Zolla-Pazner S (1991) Epitope mapping of two immunodominant domains of gp41, the transmembrane protein of human immunodeficiency virus type 1, using ten human monoclonal antibodies. J Virol 65:4832–4838

    CAS  PubMed  Google Scholar 

  28. Xu S, Song A, Nie J, Li X, Li J, Bao Z, Wang Y (2008) Comparative evaluation of the COBAS AmpliPrep/COBAS TaqMan HIV type 1 test (CAP/CTM) and VERSANT HIV type 1 RNA 3.0 assay (bDNA) for quantifying HIV type 1 viral loads in China. AIDS Res Hum Retroviruses 24:1365–1373

    Article  CAS  PubMed  Google Scholar 

  29. Zwick MB, Jensen R, Church S, Wang M, Stiegler G, Kunert R, Katinger H, Burton DR (2005) Anti-human immunodeficiency virus type 1 (HIV-1) antibodies 2F5 and 4E10 require surprisingly few crucial residues in the membrane-proximal external region of glycoprotein gp41 to neutralize HIV-1. J Virol 79:1252–1261

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Dr. Zhiqiang He (Fapon Biotech Inc.) for technical assistance with protein expression and Dr. Yi Ye, Feifei Dai, Qifeng Zhang and Zhi Zhang (Kinghawk Pharmaceutical Co., Ltd) for technical assistance with ELISA assays. This study was supported by the key project on infectious diseases such as AIDS, Hepatitis, Tuberculosis (grant: 2009ZX10004-801) from the Ministry of Science and Technology, China.

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Youchun Wang.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nie, J., Song, A., Xu, S. et al. The effect of human immunodeficiency virus type 1 (HIV-1) gp41 variability on antibody detection. Arch Virol 155, 1813–1822 (2010). https://doi.org/10.1007/s00705-010-0775-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-010-0775-0

Keywords

Navigation