2017
DOI: 10.1128/jvi.00174-17
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Induction of a Tier-1-Like Phenotype in Diverse Tier-2 Isolates by Agents That Guide HIV-1 Env to Perturbation-Sensitive, Nonnative States

Abstract: The envelope glycoproteins (Envs) on the surfaces of HIV-1 particles are targeted by host antibodies. Primary HIV-1 isolates demonstrate different global sensitivities to antibody neutralization; tier-1 isolates are sensitive, whereas tier-2 isolates are more resistant. Single-site mutations in Env can convert tier-2 into tier-1-like viruses. We hypothesized that such global change in neutralization sensitivity results from weakening of intramolecular interactions that maintain Env integrity. Three strategies … Show more

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Cited by 12 publications
(48 citation statements)
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“…The metastability of Env creates immense challenges for structural studies and for the creation of vaccine immunogens. The pretriggered state 1 Env readily transitions into lower-energy conformational states upon removal from its native membrane environment (39)(40)(41)(42). Soluble Env trimers lacking the transmembrane region and cytoplasmic tail are labile and easily dissociate into monomers and dimers (39,(43)(44)(45)(46).…”
mentioning
confidence: 99%
“…The metastability of Env creates immense challenges for structural studies and for the creation of vaccine immunogens. The pretriggered state 1 Env readily transitions into lower-energy conformational states upon removal from its native membrane environment (39)(40)(41)(42). Soluble Env trimers lacking the transmembrane region and cytoplasmic tail are labile and easily dissociate into monomers and dimers (39,(43)(44)(45)(46).…”
mentioning
confidence: 99%
“…The above data demonstrate that Envs of diverse primary HIV-1 isolates have different sensitivities to changes in membrane lipid content. Interestingly, the 89.6 Env, which is the most sensitive of the panel to membrane lipid changes, was also recently shown to be unstable relative to the Envs of other primary isolates (1). Envs of diverse HIV-1 strains differ considerably in their inherent level of stability (77,87,141).…”
Section: Sensitivity Of Hiv-1 Strains To Cholesterol Depletion Is Assmentioning
confidence: 99%
“…Stable Envs maintain a 'closed' conformation wherein cryptic epitopes that overlap the coreceptor-binding site (CoR-BS) are not exposed. Additionally, stable Envs are more resistant to the effects of treatments that perturb protein structure, including cold denaturation and inhibitory ligands (85,246). We hypothesized that sensitivity of HIV-1 to membrane lipid changes is affected by stability of Env.…”
Section: Sensitivity Of Hiv-1 Strains To Cholesterol Depletion Is Assmentioning
confidence: 99%
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