Journal article
The lipid membrane of HIV-1 stabilizes the viral envelope glycoproteins and modulates their sensitivity to antibody neutralization
The Journal of biological chemistry, Vol.295(2), pp.348-362
01/10/2020
DOI: 10.1074/jbc.RA119.009481
PMCID: PMC6956520
PMID: 31757809
Abstract
The envelope glycoproteins (Envs) of HIV-1 are embedded in the cholesterol-rich lipid membrane of the virus. Chemical depletion of cholesterol from HIV-1 particles inactivates their infectivity. We observed that diverse HIV-1 strains exhibit a range of sensitivities to such treatment. Differences in sensitivity to cholesterol depletion could not be explained by variation in Env components known to interact with cholesterol, including the cholesterol-recognition motif and cytoplasmic tail of gp41. Using antibody-binding assays, measurements of virus infectivity, and analyses of lipid membrane order, we found that depletion of cholesterol from HIV-1 particles decreases the conformational stability of Env. It enhances exposure of partially cryptic epitopes on the trimer and increases sensitivity to structure-perturbing treatments such as antibodies and cold denaturation. Substitutions in the cholesterol-interacting motif of gp41 induced similar effects as depletion of cholesterol. Surface-acting agents, which are incorporated into the virus lipid membrane, caused similar effects as disruption of the Env-cholesterol interaction. Furthermore, substitutions in gp120 that increased structural stability of Env (
induced a "closed" conformation of the trimer) increased virus resistance to cholesterol depletion and to the surface-acting agents. Collectively, these results indicate a critical contribution of the viral membrane to the stability of the Env trimer and to neutralization resistance against antibodies. Our findings suggest that the potency of poorly neutralizing antibodies, which are commonly elicited in vaccinated individuals, may be markedly enhanced by altering the lipid composition of the viral membrane.
Details
- Title: Subtitle
- The lipid membrane of HIV-1 stabilizes the viral envelope glycoproteins and modulates their sensitivity to antibody neutralization
- Creators
- Hamid Salimi - Roy J. and Lucille A. Carver College of MedicineJacklyn Johnson - Roy J. and Lucille A. Carver College of MedicineManuel G Flores - Roy J. and Lucille A. Carver College of MedicineMichael S Zhang - Roy J. and Lucille A. Carver College of MedicineYunxia O'Malley - University of IowaJon C Houtman - University of IowaPatrick M Schlievert - University of IowaHillel Haim - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.295(2), pp.348-362
- DOI
- 10.1074/jbc.RA119.009481
- PMID
- 31757809
- PMCID
- PMC6956520
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Grant note
- T32 GM007337 / NIGMS NIH HHS R25 GM116686 / NIGMS NIH HHS T32 AI007533 / NIAID NIH HHS
- Language
- English
- Date published
- 01/10/2020
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Gastroenterology, Hepatology, Pancreatology, and Nutrition; Internal Medicine
- Record Identifier
- 9984297434602771
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