The effect of polyethylene glycol-modified lipids on the interaction of HIV-1 derived peptide–dendrimer complexes with lipid membranes

N4-hexadecyl-5′-0-(4-monomethoxytrityl)-2′-deoxycytidine-3′-hydrogenphosphonate and 5′-0-(4-monomethoxytrityl)-2′-deoxythymidine-3′-0-hydrogenphosphonate were condensed with 2′,3′-dideoxycytidine (ddC) according to the hydrogenphosphonate method to yield N4-hexadecyl-2′-deoxycytidylyl-(3′-5′)-2′,3′-dideoxycytidine (N4-hexadecyldC-ddC) and 2′-deoxythymidylyl-(3′-5′)-N4-palmitoyl-2′,3′-dideoxycytidine (dT-N4-palmddC). N4-palmitoyl-2′,3′-dideoxycytidine (N4-palmddC) was synthesized by reacting palmitic anhydride with ddC. Both dinucleoside phosphates have amphiphilic properties and represent a new class of ddC derivatives in which in the case of the dinucleosides, the ddC-5′-monophosphate is masked with lipophilic residues of variable stability. The ddC derivatives can be solubilized in water by micelle formation and, because they have lipophilic residues, they can be incorporated into the lipid membranes of liposomes. The ddC derivatives were shown to have antiviral activities comparable to those of AZT and ddC when tested in vitro against HIV-1-infected HeLa and H9 cells as well as infected human monocytes/macrophages.

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Mechanistic insights into the translocation of full length HIV-1 Tat across lipid membranes

Biochimica et Biophysica Acta (BBA) - Biomembranes ◽

10.1016/j.bbamem.2011.07.030 ◽

2011 ◽

Vol 1808 (11) ◽

pp. 2685-2693 ◽

Cited By ~ 5

Author(s):

Annegret Boll ◽

Aline Jatho ◽

Nadine Czudnochowski ◽

Matthias Geyer ◽

Claudia Steinem

Keyword(s):

Lipid Membranes ◽

Full Length ◽

Hiv 1

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Effects of HIV-1 gp41-Derived Virucidal Peptides on Virus-like Lipid Membranes

Biophysical Journal ◽

10.1016/j.bpj.2017.06.061 ◽

2017 ◽

Vol 113 (6) ◽

pp. 1301-1310 ◽

Cited By ~ 6

Author(s):

Pablo Carravilla ◽

Antonio Cruz ◽

Itziar Martin-Ugarte ◽

Itziar R. Oar-Arteta ◽

Johanna Torralba ◽

...

Keyword(s):

Lipid Membranes ◽

Hiv 1

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Self assembly of HIV-1 Gag protein on lipid membranes generates PI(4,5)P2/Cholesterol nanoclusters

Scientific Reports ◽

10.1038/srep39332 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 31

Author(s):

Naresh Yandrapalli ◽

Quentin Lubart ◽

Hanumant S. Tanwar ◽

Catherine Picart ◽

Johnson Mak ◽

...

Keyword(s):

Self Assembly ◽

Lipid Membranes ◽

Gag Protein ◽

Hiv 1

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Binding of the C-terminal domain of the HIV-1 capsid protein to lipid membranes: a biophysical characterization

Biochemical Journal ◽

10.1042/bj20051487 ◽

2006 ◽

Vol 394 (1) ◽

pp. 345-353 ◽

Cited By ~ 7

Author(s):

Francisco N. Barrera ◽

Estefanía Hurtado-Gómez ◽

María C. Lidón-Moya ◽

José L. Neira

Keyword(s):

Capsid Protein ◽

Lipid Membranes ◽

Three Dimensional ◽

Lipid Vesicles ◽

Lipid Binding ◽

Scanning Calorimetry ◽

Form Part ◽

Virion Envelope ◽

Hiv 1

The capsid protein, CA, of HIV-1 forms a capsid that surrounds the viral genome. However, recent studies have shown that an important proportion of the CA molecule does not form part of this capsid, and its location and function are still unknown. In the present work we show, by using fluorescence, differential scanning calorimetry and Fourier-transform infrared spectroscopy, that the C-terminal region of CA, CA-C, is able to bind lipid vesicles in vitro in a peripheral fashion. CA-C had a greater affinity for negatively charged lipids (phosphatidic acid and phosphatidylserine) than for zwitterionic lipids [PC/Cho/SM (equimolar mixture of phosphatidylcholine, cholesterol and sphingomyelin) and phosphatidylcholine]. The interaction of CA-C with lipid membranes was supported by theoretical studies, which predicted that different regions, occurring close in the three-dimensional CA-C structure, were responsible for the binding. These results show the flexibility of CA-C to undergo conformational rearrangements in the presence of different binding partners. We hypothesize that the CA molecules that do not form part of the mature capsid might be involved in lipid-binding interactions in the inner leaflet of the virion envelope.

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Binding Mechanism of the Matrix Domain of HIV-1 Gag on Lipid Membranes

10.1101/2020.05.06.080945 ◽

2020 ◽

Author(s):

V. Monje-Galvan ◽

Gregory A. Voth

Keyword(s):

Lipid Bilayers ◽

Lipid Membranes ◽

Electrostatic Interactions ◽

Membrane Dynamics ◽

Collective Effects ◽

Gag Protein ◽

Matrix Domain ◽

Viral Budding ◽

The Matrix ◽

Hiv 1

AbstractAggregation of the HIV-1 Gag protein onto the plasma membrane (PM) enables viral budding and infection propagation. Gag assembly at the membrane interface is mediated by its matrix domain (MA), the Myristoylated (Myr) N-terminus. MA targets the PM through electrostatic interactions, mainly at its highly-basic-region (HBR). The mechanism of Myr insertion and its role in protein-membrane dynamics remains unclear. Using all-atom molecular dynamics, we examined an MA unit in the vicinity of lipid bilayers that model different characteristics of the PM. Interaction with PIP2 and PS lipids is highly favored around the HBR, and is enough to keep the protein bound. Additionally, we simulated three MA units near our bilayers and quantified the collective effects of free monomers vs. formed trimers on Myr insertion events. Micro-second-long trajectories allowed us to observe Myr insertion, propose a mechanism, quantify specific interactions with lipids, and examine the response of the local membrane environment.

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Use of Tri-Chloroacetic Acid /Acetone/polyethylene glycol for protein purification from HIV-1 infected human plasma

10.21203/rs.2.11976/v1 ◽

2019 ◽

Author(s):

Sushanta Kumar Barik ◽

Keshar Kunja Mohanty ◽

Deepa Bisht ◽

Partha Sarathi Mohanty ◽

Shripad Patil ◽

...

Keyword(s):

Molecular Weight ◽

Polyethylene Glycol ◽

Protein Purification ◽

Human Plasma ◽

Water Soluble ◽

Low Molecular Weight ◽

High Concentration ◽

Low Concentration ◽

Low Molecular Weight Proteins ◽

Hiv 1

Abstract Human plasma contains high amount of abundant proteins like albumin and globulin. Normally, the proteins having potential for biomarkers are present in very low concentration in human plasma. To resolve the low concentration proteins in polyacrylamide gel, the removal of high abundant proteins from plasma are very essential. Polyethylene glycol is a nontoxic, water soluble synthetic polymer has several applications in chemical and biomedical industries. Various molecular variants of poly ethylene glycol is available and used in protein purification. The mechanism behind the use of high concentration of polyethylene glycol is it binds the molecule in more compact or interpenetrates forming a gel like network surrounding the molecule. Polyethylene glycol -6000 removes the high abundant proteins like Albumin and Globulin in the HIV -1 infected plasma samples and concentrates the low molecular weight proteins as the low molecular weight proteins are essential in biomarker study.

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Self assembly of HIV-1 Gag protein on lipid membranes generates PI(4,5)P2/Cholesterol nanoclusters

10.1101/081737 ◽

2016 ◽

Author(s):

Naresh Yandrapalli ◽

Quentin Lubart ◽

Hanumant S. Tanwar ◽

Catherine Picart ◽

Johnson Mak ◽

...

Keyword(s):

Plasma Membrane ◽

Self Assembly ◽

Lipid Membranes ◽

Membrane Lipids ◽

Virus Assembly ◽

Specific Interaction ◽

Membrane Lipid ◽

Gag Protein ◽

Gag Polyprotein ◽

Hiv 1

AbstractThe self-assembly of HIV-1 Gag polyprotein at the inner leaflet of the cell host plasma membrane is the key orchestrator of virus assembly. The binding between Gag and the plasma membrane is mediated by specific interaction of the Gag matrix domain and the PI(4,5)P2 lipid (PIP2). It is unknown whether this interaction could lead to local reorganization of the plasma membrane lipids. In this study, using model membranes, we examined the ability of Gag to segregate specific lipids upon self-assembly. We show for the first time that Gag self-assembly is responsible for the formation of PIP2 lipid nanoclusters, enriched in cholesterol but not in sphingomyelin. We also show that Gag mainly partition into liquid-disordered domains of these lipid membranes. Our work strongly suggests that, instead of targeting pre-existing plasma membrane lipid domains, Gag is more prone to generate PIP2/Cholesterol lipid nanodomains at the inner leaflet of the plasma membrane during early events of virus assembly.

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