title: A new paradigm in molecular recognition? Specific antibody binding to membrane-inserted HIV-1 epitopes.
abstract: The conserved membrane proximal external region (MPER), adjacent to the transmembrane domain (TMD) of human immunodeficiency virus type-1 (HIV-1) gp41 glycoprotein subunit, is accessible to the broadly neutralizing 4E10 and 2F5 monoclonal antibodies (mAbs) and, therefore, constitutes a potential target for vaccine design. This gp41 domain is postulated to be functional during the Env glycoprotein-mediated fusion reaction by destabilizing the highly rigid viral envelope. To perform this task, the aromatic-rich MPER is believed to insert into the interfacial region of the viral membrane external monolayer, thereby inducing the restructuring of the lipid bilayer required for fusion-pore opening. This model predicts that: (i) 2F5 and 4E10 mAbs are capable of binding epitopes inserted into the membrane interface; (ii) in-membrane binding will result in effective blocking of MPER membrane activity; and (iii) both processes, in-membrane recognition and blocking of membrane activity, can be modulated by altering both the lipid composition and the MPER amino acid sequence. We review here recently reported experimental data consistent with those predictions, and further speculate on their relevance for prospective anti-HIV vaccine development.
authors.affiliation: Biophysics Unit (CSIC-UPV/EHU) and Biochemistry Department, University of the Basque Country, P.O. Box 644, 48080 Bilbao, Spain. gbpniesj@lg.ehu.es
authors.forename: José L
authors.initials: JL
authors.lastname: Nieva
authors.forename: Beatriz
authors.initials: B
authors.lastname: Apellaniz
authors.forename: Nerea
authors.initials: N
authors.lastname: Huarte
authors.forename: Maier
authors.initials: M
authors.lastname: Lorizate
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D010455:Peptides / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D010455:Peptides