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  • Oral presentation
  • Open Access

Detection of Novel Neutralizing Antibody Reactivities Against The Membrane Proximal External Region (MPER) of gp41 in HIV-1 Infected Humans

Retrovirology20052 (Suppl 1) :S102

https://doi.org/10.1186/1742-4690-2-S1-S102

  • Published:

Keywords

  • Parental Virus
  • 4E10 Epitope
  • Membrane Proximal External Region
  • IC50 Titer

Background

Previously, we employed site-directed mutagenesis to introduce HIV-1 4E10 and 2F5 epitopes into the corresponding region of a functional HIV-2 envelope glycoproteins (AIDS Vaccine 2005, abstract #A210). The resulting "chimeric" viruses were used to screen HIV-1 infected human plasma for 4E10 or 2F5-like neutralizing antibodies (Nabs). Among 177 subjects infected with HIV-1 representing ten different subtypes or circulating recombinant forms, none had significant Nab titers directed toward these epitopes.

Materials and methods

Here, we tested the same HIV-1 positive plasma specimens for neutralizing activity against chimeric HIV-2 viruses in which we substituted the complete 25 amino acid HIV-1 MPER (designated clone C1) or non-overlapping amino-terminal or carboxy-terminal portions of it (designated C3 and C4, respectively) using a single-cycle infectivity assay (Nature 422:307, 2003).

Results

HIV-2 viruses containing the C1, C3 or C4 MPER, and the parental virus HIV-2/7312A, were infectious and equally susceptible to neutralization by T1249, sCD4, the anti-HIV-2 Env mAb 1.7A, and polyclonal anti-HIV-2 antibodies. This result demonstrates that none of the chimeric HIV-2 viruses was "globally sensitive" to neutralization. Surprisingly, 60 out of 165 (36%) of HIV-1 plasmas tested contained MPER specific Nabs. IC50 titers ranged from 0.0005–0.02 (mean 0.006; median 0.004; standard deviation 0.004). Anti-MPER Nab reactivities were mapped to C3 (6 subjects) or C4 (14 subjects) regions of the HIV-1 MPER or to epitopes spanning them (13 subjects). None of the 60 subjects with Nabs to C1, C3, or C4 had antibodies that neutralized HIV-2 viruses containing 2F5 or 4E10 epitopes only.

Conclusion

These results indicate that the MPER of HIV-1 elicits Nab responses in a substantial proportion of infected patients and that the epitopes recognized by these Nabs are distinct from those recognized by 4E10 or 2F5.

Notes

Authors’ Affiliations

(1)
Univ. of Alabama, B'ham, AL, USA

Copyright

© The Author(s) 2005

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