Web of Science: 7 citations, Scopus: 6 citations, Google Scholar: citations
The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype
Cunyat, Francesc (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Marfil, Silvia (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
García, Elisabet (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Svicher, Valentina (Department of Experimental Medicine. University of "Tor Vergata," Rome, Italy)
Pérez-Alvárez, Nuria (Statistics and Operation Research Department, Universitat Politècnica de Catalunya, Barcelona, Spain)
Curriu, Marta (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Perno, Carlo Federico (Department of Experimental Medicine. University of "Tor Vergata," Rome, Italy)
Clotet, Bonaventura (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Blanco, Julià (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Cabrera, Cecilia (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Universitat Autònoma de Barcelona

Date: 2012
Abstract: Resistance to the fusion inhibitor enfuvirtide (ENF) is achieved by changes in the gp41 subunit of the HIV envelope glycoprotein (Env). Specific ENF-associated mutational pathways correlate with immunological recovery, even after virological failure, suggesting that the acquisition of ENF resistance alters gp41 pathogenicity. To test this hypothesis, we have characterized the expression, fusion capability, induction of CD4 + T cell loss and single CD4 + T cell death of 48 gp41 proteins derived from three patients displaying different amino acids (N, T or I) at position 140 that developed a V38A mutation after ENF-based treatment. In all cases, intra-patient comparison of Env isolated pre- or post-treatment showed comparable values of expression and fusogenic capacity. Furthermore, Env with either N or T at position 140 induced comparable losses of CD4 + T-cells, irrespective of the residue present at position 38. Conversely, Env acquiring the V38A mutation in a 140I background induced a significantly reduced loss of CD4 + T cells and lower single-cell death than did their baseline controls. No altered ability to induce single-cell death was observed in the other clones. Overall, primary gp41 proteins with both V38A and N140I changes showed a reduced ability to induce single cell death and deplete CD4 + T cells, despite maintaining fusion activity. The specificity of this phenotype highlights the relevance of the genetic context to the cytopathic capacity of Env and the role of ENF-resistance mutations in modulating viral pathogenicity in vivo, further supporting the hypothesis that gp41 is a critical mediator of HIV pathogenesis.
Note: Altres ajuts: This work was supported by the FIS project 07/0418 (to CC), the Spanish AIDS network, "RIS, Red Temática Cooperativa de Investigación en SIDA (RD06/0006)" and the CHAIN European Consortium. C. Cabrera and J. Blanco are researchers from Fundació Institut de Recerca en Ciències de la Salut Germans Trias i Pujol supported by the Health Department of the Catalan Government (Generalitat de Catalunya). F. Cunyat is supported by the FIS project 07/0418 and VS is supported by grants from CHAIN, Collaborative HIV and Anti-HIV Drug-Resistance Network, Integrated Project no.223131, funded by the European-Commission Framework-7 Program. MC is supported by a RIS contract. This work is part of the PhD thesis of F. Cunyat at Universitat Autònoma de Barcelona, Barcelona, Spain.
Note: Número d'acord de subvenció EC/07/0418
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès
Document: article ; recerca ; publishedVersion ; article ; publishedVersion
Subject: HIV ; Gp41 ; Enfuvirtide ; Single cell death ; Fusogenicity
Published in: Retrovirology, Vol. 9 (february 2012) , p. 15, ISSN 1742-4690

DOI: 10.1186/1742-4690-9-15
PMID: 22333046


11 p, 548.7 KB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles

 Record created 2018-01-26, last modified 2021-02-21



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