Interactions of peptide triazole thiols with Env gp120 induce irreversible breakdown and inactivation of HIV-1 virions

Retrovirology
Arangassery Rosemary BastianIrwin M Chaiken

Abstract

We examined the underlying mechanism of action of the peptide triazole thiol, KR13 that has been shown previously to specifically bind gp120, block cell receptor site interactions and potently inhibit HIV-1 infectivity. KR13, the sulfhydryl blocked KR13b and its parent non-sulfhydryl peptide triazole, HNG156, induced gp120 shedding but only KR13 induced p24 capsid protein release. The resulting virion post virolysis had an altered morphology, contained no gp120, but retained gp41 that bound to neutralizing gp41 antibodies. Remarkably, HIV-1 p24 release by KR13 was inhibited by enfuvirtide, which blocks formation of the gp41 6-helix bundle during membrane fusion, while no inhibition of p24 release occurred for enfuvirtide-resistant virus. KR13 thus appears to induce structural changes in gp41 normally associated with membrane fusion and cell entry. The HIV-1 p24 release induced by KR13 was observed in several clades of HIV-1 as well as in fully infectious HIV-1 virions. The antiviral activity of KR13 and its ability to inactivate virions prior to target cell engagement suggest that peptide triazole thiols could be highly effective in inhibiting HIV transmission across mucosal barriers and provide a novel probe to understand bioc...Continue Reading

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Citations

Dec 30, 2015·Biochemistry·Ramalingam Venkat Kalyana SundaramIrwin M Chaiken
Nov 26, 2015·Future Medicinal Chemistry·Irwin Chaiken, Adel A Rashad
Nov 6, 2014·The Journal of Biological Chemistry·Arangassery Rosemary BastianIrwin Chaiken
Feb 5, 2021·ACS Chemical Biology·Althea GaffneyIrwin Chaiken
Jan 8, 2021·ACS Chemical Biology·Althea GaffneyIrwin Chaiken

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Methods Mentioned

BETA
surface plasmon resonance
ELISA
density gradient fractionation
Transmission electron microscopy
chip
Surface
biosensor

Software Mentioned

Origin
Image J
BiaEvaluation
Origin Pro

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