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. 2004 Mar;78(5):2627-31.
doi: 10.1128/jvi.78.5.2627-2631.2004.

Binding of the 2F5 monoclonal antibody to native and fusion-intermediate forms of human immunodeficiency virus type 1 gp41: implications for fusion-inducing conformational changes

Eve de Rosny  1 , Russell Vassell, Shibo Jiang, Renate Kunert, Carol D Weiss
Affiliations

Binding of the 2F5 monoclonal antibody to native and fusion-intermediate forms of human immunodeficiency virus type 1 gp41: implications for fusion-inducing conformational changes

Eve de Rosny et al. J Virol. 2004 Mar.

Abstract

We investigated how the broadly neutralizing monoclonal antibody 2F5 affects the human immunodeficiency virus type 1 envelope glycoprotein as it undergoes receptor-induced conformational changes and show that 2F5 binds both native and fusion-intermediate conformations, suggesting inhibition of a late step in virus entry. We also demonstrate conformational changes in the C heptad of gp41.

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Figures

FIG. 1.
FIG. 1.
(A) Linear representation of gp41 domains and approximate localization of epitopes for 2F5 and D50 monoclonal antibodies (MAbs). Numbering is based on the HIV-1 HXB2 strain according to the Los Alamos National Laboratory database. N36 peptide contains the following residues (546 to 581): SGIVQQQNNLLRAIEAQQHLLQLTVWGIKQLQARIL. C34 peptide contains the following residues (628 to 661): WMEWDREINNYTSLIHSLIEESQNQQEKNEQELL. FP, fusion peptide; TM, transmembrane domain. (B) Model of HIV-1 entry involving conformational changes in gp41. Brackets show a putative fusion intermediate that is trapped with the C-heptad repeat peptide, preventing formation of the six-helix bundle. (C) Schematic representation of the six-helix bundle structure generated by self assembly of the N- and C-heptad repeat domains.
FIG. 2.
FIG. 2.
CD4 dependence of antibody binding to gp41. 2F5 and D50 MAbs were used to immunoprecipitate gp41 on the surface of Env-expressing cells (A) or virions (B) in the absence (−) or presence (+) of sCD4. Blots were probed with an antibody to gp41. Control is an immunoblot of Env-expressing cell lysate. Results shown are representative of at least three independent experiments.
FIG. 3.
FIG. 3.
Antibody binding to the fusion intermediate. 2F5 (A) and D50 (B) MAbs were used to immunoprecipitate peptide-trapped Env from gp41 expressed on cell surface with (+) or without (−) sCD4 in the absence (−) or presence (+) of the C34 or N36 peptide. The C34 peptide binds the N heptad of gp41, and the N36 peptide binds the C heptad of gp41, preventing formation of the six-helix bundle using endogenous heptad repeats from gp41. Blots were probed with an antibody to gp41. Results shown are representative of at least three independent experiments.
FIG. 4.
FIG. 4.
Antibodies binding to the six-helix bundle after pretreatment with 2F5. (A) Increasing concentrations of the NC-1 MAb or anti-six-helix bundle antibodies (α-b1, α-b2) are able to immunoprecipitate gp41 equally well in the presence or absence of pretreatment with 2F5. (B) Increasing concentrations of 2F5 do not impair the ability of the NC-1 to precipitate gp41. Blots were probed with an antibody to gp41. Control is an immunoblot of Env-expressing cell lysate. Results shown are representative of at least three independent experiments.
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