2003
DOI: 10.1128/jvi.77.3.1666-1671.2003
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Peptides Trap the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Fusion Intermediate at Two Sites

Abstract: HR peptide and compare these data with inhibition by a C-HR peptide. Using intact envelope glycoprotein (Env) under fusogenic conditions, we show that the N-HR peptide preferentially binds receptor-activated Env and that CD4 binding is sufficient for triggering conformational changes that allow the peptide to bind Env, results similar to those seen with the C-HR peptide. However, activation by both CD4 and chemokine receptors further enhances Env binding by both peptides. We also show that a nonconservative mu… Show more

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Cited by 132 publications
(118 citation statements)
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“…The exposure of this element after CD4 binding could allow the subsequent interaction with the gp41 HR2 region to form the six-helix bundle, a process that is thought to promote viral and target cell membrane fusion (4)(5)(6). Importantly, in contrast to previous studies (19,20), we have designed our assay to rule out gp120 shedding as an explanation for CD4-induced exposure of gp41 moieties. The relevance of CD4-induced gp120 shedding to HIV-1 entry is doubtful, given the documented necessity of chemokine receptor binding to infection (11)(12)(13)(14)(15); gp120 shedding may represent an exaggerated or aberrant response to CD4 binding that ultimately inactivates the envelope glycoprotein spike (16).…”
Section: Discussionmentioning
confidence: 89%
See 2 more Smart Citations
“…The exposure of this element after CD4 binding could allow the subsequent interaction with the gp41 HR2 region to form the six-helix bundle, a process that is thought to promote viral and target cell membrane fusion (4)(5)(6). Importantly, in contrast to previous studies (19,20), we have designed our assay to rule out gp120 shedding as an explanation for CD4-induced exposure of gp41 moieties. The relevance of CD4-induced gp120 shedding to HIV-1 entry is doubtful, given the documented necessity of chemokine receptor binding to infection (11)(12)(13)(14)(15); gp120 shedding may represent an exaggerated or aberrant response to CD4 binding that ultimately inactivates the envelope glycoprotein spike (16).…”
Section: Discussionmentioning
confidence: 89%
“…It has been hypothesized that, for enveloped viruses such as HIV-1 that fuse viral and target cell membranes at neutral pH, receptor binding by the exterior envelope glycoprotein serves as the trigger that activates the fusogenic functions of the transmembrane envelope glycoprotein (3-6). Indeed, sCD4 binding to the HIV-1 envelope glycoproteins has been reported to result in the exposure of gp41 elements (18)(19)(20). However, as noted above, sCD4 binding can also induce gp120 shedding (16), allowing gp41 exposure by a process not obviously related to virus entry.…”
Section: The Antiviral Activity Of Bms-806 Is Not Due To Inhibition Omentioning
confidence: 99%
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“…Each protomer composing the trimeric Env spike thus consists of a gp120 exterior subunit and a gp41 transmembrane subunit. The sequential binding of gp120 to the target cell receptors, CD4 and chemokine receptor (either CCR5 or CXCR4), allows the metastable Env complex to transit into fusion-active conformations (3,(8)(9)(10)(11). These conformational transitions expose the hydrophobic gp41 N-terminal fusion peptide, promoting its insertion into the target cell membrane, and further permit the formation of a highly stable gp41 six-helix bundle that mediates viral-cell membrane fusion (12)(13)(14).…”
mentioning
confidence: 99%
“…[44][45][46][47] Here we describe a method for potentially increasing the efficacy of current viral entry inhibitors without increasing the complexity of production. In fact, in most cases ligation will simplify inhibitor design and assembly.…”
Section: Chemoselective Ligationmentioning
confidence: 99%