Publication
An ancestral HIV-2/simian immunodeficiency virus peptide with potent HIV-1 and HIV-2 fusion inhibitor activity
| dc.contributor.author | Borrego, Pedro | |
| dc.contributor.author | Calado, Rita | |
| dc.contributor.author | Marcelino, José M. | |
| dc.contributor.author | Pereira, Patrícia | |
| dc.contributor.author | Quintas, Alexandre | |
| dc.contributor.author | Barroso, Helena | |
| dc.contributor.author | Taveira, Nuno | |
| dc.date.accessioned | 2014-05-29T10:35:18Z | |
| dc.date.available | 2014-05-29T10:35:18Z | |
| dc.date.issued | 2013-04 | |
| dc.description.abstract | "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." | por |
| dc.identifier.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 | por |
| dc.identifier.issn | 0269-9370 | |
| dc.identifier.issn | 1473-5571 | |
| dc.identifier.uri | http://hdl.handle.net/10400.26/6424 | |
| dc.language.iso | eng | por |
| dc.peerreviewed | yes | por |
| dc.publisher | Wolters Kluwer / LWW | por |
| dc.relation.publisherversion | http://journals.lww.com/aidsonline/Fulltext/2013/04240/An_ancestral_HIV_2_simian_immunodeficiency_virus.4.aspx | por |
| dc.subject | Ancestral P3 peptide | por |
| dc.subject | Inhibition of HIV-1 and HIV-2 cell fusion and entry | por |
| dc.subject | P3 antigenic reactivity | por |
| dc.subject | P3 mechanism of action | por |
| dc.subject | Resistance to P3 | por |
| dc.title | An ancestral HIV-2/simian immunodeficiency virus peptide with potent HIV-1 and HIV-2 fusion inhibitor activity | por |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-FAR%2F115290%2F2009/PT | |
| oaire.citation.endPage | 1090 | por |
| oaire.citation.startPage | 1081 | por |
| oaire.citation.title | AIDS | por |
| oaire.citation.volume | 27 | por |
| oaire.fundingStream | 3599-PPCDT | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| rcaap.rights | openAccess | por |
| rcaap.type | article | por |
| relation.isProjectOfPublication | 15aded3d-70a1-4e02-8508-f5e6a4e56f9a | |
| relation.isProjectOfPublication.latestForDiscovery | 15aded3d-70a1-4e02-8508-f5e6a4e56f9a |