Journal article
Impact of HIV-1 Membrane Cholesterol on Cell-Independent Lytic Inactivation and Cellular Infectivity
Biochemistry (Easton), v 55(3), pp 447-458
26 Jan 2016
PMID: 26713837
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Peptide triazole thiols (PTTs) have been found previously to bind to HIV-1 Env spike gp120 and cause irreversible virus inactivation by shedding gp120 and lytically releasing luminal capsid protein p24. Since the virions remain visually intact, lysis appears to occur via limited membrane destabilization. To better understand the PTT-triggered membrane transformation involved, we investigated the role of envelope cholesterol on p24 release by measuring the effect of cholesterol depletion using methyl beta-cyclodextrin (MβCD). An unexpected bell-shaped response of PTT-induced lysis to [MβCD] was observed, involving lysis enhancement at low [MβCD] vs loss of function at high [MβCD]. The impact of cholesterol depletion on PTT-induced lysis was reversed by adding exogenous cholesterol and other sterols that support membrane rafts, while sterols that do not support rafts induced only limited reversal. Cholesterol depletion appears to cause a reduced energy barrier to lysis as judged by decreased temperature dependence with MβCD. Enhancement/replenishment responses to [MβCD] also were observed for HIV-1 infectivity, consistent with a similar energy barrier effect in the membrane transformation of virus cell fusion. Overall, the results argue that cholesterol in the HIV-1 envelope is important for balancing virus stability and membrane transformation, and that partial depletion, while increasing infectivity, also makes the virus more fragile. The results also reinforce the argument that the lytic inactivation and infectivity processes are mechanistically related and that membrane transformations occurring during lysis can provide an experimental window to investigate membrane and protein factors important for HIV-1 cell entry.
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Details
- Title
- Impact of HIV-1 Membrane Cholesterol on Cell-Independent Lytic Inactivation and Cellular Infectivity
- Creators
- Ramalingam Venkat Kalyana Sundaram - School of Biomedical Engineering, Science and Health Systems, Drexel University , Philadelphia, Pennsylvania 19104, United StatesHuiyuan Li - Shared Research Facilities, West Virginia University , Morgantown, West Virginia 26506, United StatesLauren Bailey - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine , Philadelphia, Pennsylvania 19102, United StatesAdel A Rashad - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine , Philadelphia, Pennsylvania 19102, United StatesRachna Aneja - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine , Philadelphia, Pennsylvania 19102, United StatesKarl Weiss - Department of Chemical and Biological Engineering, Drexel University , Philadelphia, Pennsylvania 19104, United StatesJames Huynh - Department of Biological Sciences, Drexel University , Philadelphia, Pennsylvania 19104, United StatesArangaserry Rosemary Bastian - School of Biomedical Engineering, Science and Health Systems, Drexel University , Philadelphia, Pennsylvania 19104, United StatesElisabeth Papazoglou - School of Biomedical Engineering, Science and Health Systems, Drexel University , Philadelphia, Pennsylvania 19104, United StatesCameron Abrams - Department of Chemical and Biological Engineering, Drexel University , Philadelphia, Pennsylvania 19104, United StatesSteven Wrenn - Department of Chemical and Biological Engineering, Drexel University , Philadelphia, Pennsylvania 19104, United StatesIrwin Chaiken - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine , Philadelphia, Pennsylvania 19102, United States
- Publication Details
- Biochemistry (Easton), v 55(3), pp 447-458
- Publisher
- American Chemical Society; Washington, DC
- Grant note
- P01 GM056550 / NIGMS NIH HHS R01GM115249 / NIGMS NIH HHS R01 GM115249 / NIGMS NIH HHS R01AI048117 / NIAID NIH HHS R01 AI048117 / NIAID NIH HHS P01GM56550 / NIGMS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Chemical and Biological Engineering
- Web of Science ID
- WOS:000368950200004
- Scopus ID
- 2-s2.0-84956783015
- Other Identifier
- 991014877943704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology