Mechanism of HIV entry: surface stiffnes and steric defense.

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Publication Type thesis
School or College School of Medicine
Department Biochemistry
Author Shi, Yu.
Title Mechanism of HIV entry: surface stiffnes and steric defense.
Date 2007-12
Description HIV undergoes a maturation process required for infectivity after leaving the cell. Significant internal morphological rearrangements occur during the maturation process, converting the immature HIV particle with a thick protein shell into a mature particle with a thin protein shell and a prominent conical core. In this study, we explored the linkage between virion morphology and mechanical properties during maturation. Our results showed that the stiffness of HIV drops dramatically during maturation, and that there is a correlation between virion stiffness and entry ability. We also showed that virion stiffness is mainly regulated by the ENV CT domain. During HIV entry, HIV Env (gp120/gp41 complex undergoes a series of conformational changes that induce viral and target cell membrane fusion. Membrane fusion is driven by the formation of gp41 six-helix bundle composed of the N-trimer region surrounded by three helices from the C-peptide region (C-peptides). Prevention of six-helix bundle formation inhibits membrane fusion and viral entry. This critical role in entry and its highly conserved sequences make the gp41 N-trimer a key drug target. Gp41 C-peptides bind the N-trimer and potently inhibit HIV entry by preventing binding of the endogenous C-peptide region. Extensive efforts have been made to find potent broadly neutralizing Abs against the N-trimer, but without success. Our lab previously demonstrated that there is a steric block on the viral side of the N-trimer region, which may explain why such Abs are difficult to discover.
Type Text
Publisher University of Utah
Subject HIV (Viruses); Etiology
Subject MESH HIV; Membrane Fusion
Dissertation Institution University of Utah
Dissertation Name MS
Language eng
Relation is Version of Digital reproduction of "Mechanism of HIV entry: surface stiffnes and steric defense." Spencer S. Eccles Health Sciences Library. Print version of "Mechanism of HIV entry: surface stiffnes and steric defense." available at J. Willard Marriott Library Special Collection. .QR6.5 2007 .S48.
Rights Management © Yu Shi.
Format Medium application/pdf
Identifier us-etd2,43
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
ARK ark:/87278/s6sn0qnd
Setname ir_etd
Date Created 2012-04-23
Date Modified 2021-05-06
ID 193973
Reference URL