%0 Journal Article
%T The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype
%A Francesc Cunyat
%A Silvia Marfil
%A Elisabet Garc¨ªa
%A Valentina Svicher
%A Nuria P¨¦rez-Alv¨¢rez
%A Marta Curriu
%A Carlo Perno
%A Bonaventura Clotet
%A Juli¨¤ Blanco
%A Cecilia Cabrera
%J Retrovirology
%D 2012
%I BioMed Central
%R 10.1186/1742-4690-9-15
%X 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.HIV infection causes a progressive depletion of CD4+ T cells, which leads to the development of AIDS [1,2]. Although CD4+ T cell loss in HIV infection is a multifaceted process [3-5], the death of bystander CD4+ T cells seems to be one of the main contributors to HIV-induced pathogenesis [6-8]. Various mechanisms have been proposed to explain the destruction of bystander CD4+ T cells, including apoptosis, autophagy or abortive infection [6,8-11]. The HIV envelope (Env) glycoprotein, which mediates viral entry into the host cell by fusion of the viral and host cell membranes (reviewed in [12-14]), is one of the viral factors involved in the death of both infected [15] and bystander cells [7,8,16]. The Env complex is composed of two non-covalently linked subunits, namely, the surface glycoprotein (gp120) and the transmembrane glycoprotein (gp41), and is displayed as heterotrimers on the surface of virions and infected cells [14,17-20]. Viral entry is a multistep phenomenon
%K HIV
%K gp41
%K enfuvirtide
%K single cell death
%K fusogenicity
%U http://www.retrovirology.com/content/9/1/15