Loading...
Publication
An ancestral HIV-2/simian immunodeficiency virus peptide with potent HIV-1 and HIV-2 fusion inhibitor activity
| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| 445.68 KB | Adobe PDF |
Advisor(s)
Abstract(s)
"Objectives: To produce new fusion inhibitor peptides for HIV-1 and HIV-2 based on
ancestral envelope sequences.
Methods: HIV-2/simian immunodeficiency virus (SIV) ancestral transmembrane
protein sequences were reconstructed and ancestral peptides were derived from the
helical region 2 (HR2). The activity of one ancestral peptide (named P3) was examined
against a panel of HIV-1 and HIV-2 primary isolates in TZM-bl cells and peripheral
blood mononuclear cells and compared to T-20. Peptide secondary structure was
analyzed by circular dichroism. Resistant viruses were selected and resistance
mutations were identified by sequencing the env gene.
Results: P3 has 34 residues and overlaps the N-terminal pocket-binding region and
heptad repeat core of HR2. In contrast to T-20, P3 forms a typical a-helical structure in
solution, binds strongly to the transmembrane protein, and potently inhibits both HIV-2
(mean IC50, 63.8 nmol/l) and HIV-1 (11 nmol/l) infection, including T-20-resistant
isolates. The N43K mutation in the HR1 region of HIV-1 leads to 120-fold resistance
to P3 indicating that the HR1 region in transmembrane glycoprotein is the target of P3.
No HIV-2-resistant mutations could be selected by P3 suggesting that the genetic barrier
to resistance is higher in HIV-2 than in HIV-1. HIV-1-infected patients presented
significantly lower P3-specific antibody reactivity compared to T-20.
Conclusion: P3 is an HIV-2/SIV ancestral peptide with low antigenicity, high stability,
and potent activity against both HIV-1, including variants resistant to T-20, and HIV-2.
Similar evolutionary biology strategies should be explored to enhance the production of
antiviral peptide drugs, microbicides, and vaccines."
Description
Keywords
Ancestral P3 peptide Inhibition of HIV-1 and HIV-2 cell fusion and entry P3 antigenic reactivity P3 mechanism of action Resistance to P3
Citation
This is a non-final version of an article published in final form in AIDS: 24 April 2013 - Volume 27 - Issue 7 - p 1081–1090 doi: 10.1097/QAD.0b013e32835edc1d