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Cholesterol in the Viral Membrane is a Molecular Switch Governing HIV‐1 Env Clustering
- Source :
- Digital.CSIC. Repositorio Institucional del CSIC, instname, Advanced Science, Vol 8, Iss 3, Pp n/a-n/a (2021), Advanced Science
- Publication Year :
- 2020
- Publisher :
- Wiley-Blackwell, 2020.
-
Abstract
- HIV‐1 entry requires the redistribution of envelope glycoproteins (Env) into a cluster and the presence of cholesterol (chol) in the viral membrane. However, the molecular mechanisms underlying the specific role of chol in infectivity and the driving force behind Env clustering remain unknown. Here, gp41 is demonstrated to directly interact with chol in the viral membrane via residues 751–854 in the cytoplasmic tail (CT751–854). Super‐resolution stimulated emission depletion (STED) nanoscopy analysis of Env distribution further demonstrates that both truncation of gp41 CT751–854 and depletion of chol leads to dispersion of Env clusters in the viral membrane and inhibition of virus entry. This work reveals a direct interaction of gp41 CT with chol and indicates that this interaction is an important orchestrator of Env clustering.<br />The authors are grateful to Barbara Müller, N. Landau, and Tom Hope for providing the plasmids pCHIV and pCAGGS NL4‐3 Env, pMM310, and peGFP‐Vpr, respectively. Proteomic analysis was performed by the SGIKER service of the University of the Basque Country. The authors would like to thank Advanced Light Microscopy Unit at the Centre for Genomic Regulation (CRG), Barcelona, Spain for the access to Leica STED microscope. The following reagents were obtained through the NIH AIDS Reagent Program (Division of NIAID, NIH): Anti‐HIV‐1 gp41 Hybridome (Chessie 8) (Cat# 526) from Dr. George Lewis; Antiviral bicyclam JM‐2987 (hydrobromide salt of AMD‐3100) from NIAID, DAIDS (cat# 8128). This project was supported by the Basque Government (grant number IT1264‐19 to M.L. and F.‐X.C.) and the Spanish Ministry of Science, Innovation, and Universities (BFU‐2015‐68981‐P). This work was supported in part by the Fundación Biofísica Bizkaia and the Basque Excellence Research Centre (BERC) program of the Basque Government. J.A.N.‐G. was supported by a FI predoctoral fellowship from the Basque Government and currently by Fundación Biofísica Bizkaia. A.A. was supported by Fundación Biofísica Bizkaia. S.O. was supported by an IKASIKER fellowship from the Basque Government. J.C. was supported by European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska‐Curie grant agreement No. 793830. H.G.‐K. was supported by a grant from the Deutsche Forschungsgemeischaft within TRR86.
- Subjects :
- gp41 cytoplasmic tails
General Chemical Engineering
viruses
General Physics and Astronomy
Medicine (miscellaneous)
02 engineering and technology
010402 general chemistry
Gp41
01 natural sciences
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Viral entry
Env clustering
polycyclic compounds
General Materials Science
Protein–lipid interactions
lcsh:Science
Infectivity
Molecular switch
chemistry.chemical_classification
Full Paper
Chemistry
HIV‐1
General Engineering
STED microscopy
technology, industry, and agriculture
virus diseases
Full Papers
Viral membrane
021001 nanoscience & nanotechnology
3. Good health
0104 chemical sciences
Cell biology
Cholesterol
Cytoplasm
HIV-1
lcsh:Q
lipids (amino acids, peptides, and proteins)
0210 nano-technology
Glycoprotein
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Digital.CSIC. Repositorio Institucional del CSIC, instname, Advanced Science, Vol 8, Iss 3, Pp n/a-n/a (2021), Advanced Science
- Accession number :
- edsair.doi.dedup.....8132a3d0f491d962965b614d955dc13e