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Kennedy Epitope (KE)-dependent Retrograde Transport of Efficiently Cleaved HIV-1 Envelopes (Envs) and its Effect on Env Cell Surface Expression and Viral Particle Formation.
Das, Supratik; Parray, Hilal Ahmad; Chiranjivi, Adarsh Kumar; Kumar, Prince; Goswami, Abhishek; Bansal, Manish; Rathore, Deepak Kumar; Kumar, Rajesh; Samal, Sweety.
Afiliación
  • Das S; Infection and Immunology, Translational Research Program, 3rd Milestone, Faridabad-Gurgaon Expressway, PO box #04, Faridabad, 121001, Haryana, India. supratik@thsti.res.in.
  • Parray HA; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, PO box #04, Faridabad, 121001, Haryana, India. supratik@thsti.res.in.
  • Chiranjivi AK; Infection and Immunology, Translational Research Program, 3rd Milestone, Faridabad-Gurgaon Expressway, PO box #04, Faridabad, 121001, Haryana, India.
  • Kumar P; Infection and Immunology, Translational Research Program, 3rd Milestone, Faridabad-Gurgaon Expressway, PO box #04, Faridabad, 121001, Haryana, India.
  • Goswami A; Infection and Immunology, Translational Research Program, 3rd Milestone, Faridabad-Gurgaon Expressway, PO box #04, Faridabad, 121001, Haryana, India.
  • Bansal M; Infection and Immunology, Translational Research Program, 3rd Milestone, Faridabad-Gurgaon Expressway, PO box #04, Faridabad, 121001, Haryana, India.
  • Rathore DK; Translational Health Science and Technology Institute, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, PO box #04, Faridabad, 121001, Haryana, India.
  • Kumar R; Infection and Immunology, Translational Research Program, 3rd Milestone, Faridabad-Gurgaon Expressway, PO box #04, Faridabad, 121001, Haryana, India.
  • Samal S; Department of Biosciences and Bioengineering, Indian Institute of Technology - Roorkee, Roorkee, Uttarakhand, 247667, India.
Protein J ; 2023 Oct 04.
Article en En | MEDLINE | ID: mdl-37794304
Efficiently cleaved HIV-1 Envs are the closest mimics of functional Envs as they specifically expose only bNAb (broadly neutralizing antibody) epitopes and not non-neutralizing ones, making them suitable for developing vaccine immunogens. We have previously identified several efficiently cleaved Envs from clades A, B, C and B/C. We also described that truncation of the CT (C-terminal tail) of a subset of these Envs, but not others, impairs their ectodomain conformation/antigenicity on the cell surface in a CT conserved hydrophilic domain (CHD) or Kennedy epitope (KE)-dependent manner. Here, we report that those Envs (4 - 2.J41 and JRCSF), whose native-like ectodomain conformation/antigenicity on the cell surface is disrupted upon CT truncation, but not other Envs like JRFL, whose CT truncation does not have an effect on ectodomain integrity on the cell surface, are also defective in retrograde transport from early to late endosomes. Restoration of the CHD/KE in the CT of these Envs restores wild-type levels of distribution between early and late endosomes. In the presence of retrograde transport inhibitor Retro 2, cell surface expression of 4 - 2.J41 and JRCSF Envs increases [as does in the presence of Rab7a DN and Rab7b DN (DN: dominant negative)] but particle formation decreases for 4 - 2.J41 and JRCSF Env pseudotyped viruses. Our results show for the first time a correlation between CT-dependent, CHD/KE regulated retrograde transport and cell surface expression/viral particle formation of these efficiently cleaved Envs. Based on our results we hypothesize that a subset of these efficiently cleaved Envs use a CT-dependent, CHD/KE-mediated mechanism for assembly and release from late endosomes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Protein J Asunto de la revista: BIOQUIMICA Año: 2023 Tipo del documento: Article País de afiliación: India Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Protein J Asunto de la revista: BIOQUIMICA Año: 2023 Tipo del documento: Article País de afiliación: India Pais de publicación: Países Bajos