Details

Autor(en) / Beteiligte

• Alsahafi, Nirmin
• Bakouche, Nordine
• Kazemi, Mohsen
• Richard, Jonathan
• Ding, Shilei
• Bhattacharyya, Sudipta
• Das, Durba
• Anand, Sai Priya
• Prévost, Jérémie
• Tolbert, William D.
• Lu, Hong
• Medjahed, Halima
• Gendron-Lepage, Gabrielle
• Ortega Delgado, Gloria Gabrielle
• Kirk, Sharon
• Melillo, Bruno
• Mothes, Walther
• Sodroski, Joseph
• Smith, Amos B.
• Kaufmann, Daniel E.
• Wu, Xueling
• Pazgier, Marzena
• Rouiller, Isabelle
• Finzi, Andrés
• Munro, James B.

Titel

An Asymmetric Opening of HIV-1 Envelope Mediates Antibody-Dependent Cellular Cytotoxicity

Ist Teil von

• Cell host & microbe, 2019-04, Vol.25 (4), p.578-587.e5

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Link zum Volltext

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• The HIV-1 envelope glycoprotein (Env) (gp120-gp41)3 is the target for neutralizing antibodies and antibody-dependent cellular cytotoxicity (ADCC). HIV-1 Env is flexible, sampling different conformational states. Before engaging CD4, Env adopts a closed conformation (State 1) that is largely antibody resistant. CD4 binding induces an intermediate state (State 2), followed by an open conformation (State 3) that is susceptible to engagement by antibodies that recognize otherwise occluded epitopes. We investigate conformational changes in Env that induce ADCC in the presence of a small-molecule CD4-mimetic compound (CD4mc). We uncover an asymmetric Env conformation (State 2A) recognized by antibodies targeting the conserved gp120 inner domain and mediating ADCC. Sera from HIV+ individuals contain these antibodies, which can stabilize Env State 2A in combination with CD4mc. Additionally, triggering State 2A on HIV-infected primary CD4+ T cells exposes epitopes that induce ADCC. Strategies that induce this Env conformation may represent approaches to fight HIV-1 infection. [Display omitted] •HIV Env exists in several conformations, including an asymmetric State 2A•State 2A is difficult to trigger and is susceptible to non-neutralizing antibody attack•Sera from HIV+ individuals contain antibodies that can stabilize Env State 2A•Conditions triggering State 2A expose epitopes that induce ADCC HIV-1 envelope glycoproteins (Env) are very flexible and exist in at least three different conformational states. Alsahafi et al. characterize a fourth Env state that is efficiently recognized by antibodies capable of mediating potent antibody-dependent cellular toxicity.