scholarly journals Cell Membrane Lipid Rafts Mediate Caveolar Endocytosis of HIV-1 Tat Fusion Proteins

2003 ◽  
Vol 278 (36) ◽  
pp. 34141-34149 ◽  
Author(s):  
Antonio Fittipaldi ◽  
Aldo Ferrari ◽  
Monica Zoppé ◽  
Caterina Arcangeli ◽  
Vittorio Pellegrini ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Lipid Rafts ◽  
Fusion Proteins ◽  
Membrane Lipid ◽  
Tat Fusion Proteins ◽  
Hiv 1

scholarly journals Caveolae-Mediated internalization of extracellular HIV-1 tat fusion proteins visualized in real time

2003 ◽  
Vol 8 (2) ◽  
pp. 284-294 ◽  
Author(s):  
Aldo Ferrari ◽  
Vittorio Pellegrini ◽  
Caterina Arcangeli ◽  
Antonio Fittipaldi ◽  
Mauro Giacca ◽  
...  
Keyword(s):  
Real Time ◽  
Fusion Proteins ◽  
Tat Fusion Proteins ◽  
Hiv 1

scholarly journals Procyanidins can interact with Caco-2 cell membrane lipid rafts: Involvement of cholesterol

2013 ◽  
Vol 1828 (11) ◽  
pp. 2646-2653 ◽  
Author(s):  
Sandra V. Verstraeten ◽  
Grayson K. Jaggers ◽  
Cesar G. Fraga ◽  
Patricia I. Oteiza
Keyword(s):  
Cell Membrane ◽  
Lipid Rafts ◽  
Membrane Lipid

scholarly journals Concerted interactions between multiple gp41 trimers and the target cell lipidome may be required for HIV-1 entry

2020 ◽  
Author(s):  
Biswajit Gorai ◽  
Anil Kumar Sahoo ◽  
Anand Srivastava ◽  
Narendra M. Dixit ◽  
Prabal K. Maiti
Keyword(s):  
Cell Membrane ◽  
Host Cell ◽  
Target Cell ◽  
Cell Membranes ◽  
Molecular Level ◽  
Membrane Lipid ◽  
Coarse Grained ◽  
Free Energy Barrier ◽  
Hiv 1

ABSTRACTThe HIV-1 envelope glycoprotein gp41 mediates the fusion between viral and host cell membranes leading to virus entry and target cell infection. Despite years of research, important aspects of this process such as the number of gp41 trimers involved and how they orchestrate the rearrangement of the lipids in the apposed membranes along the fusion pathway remain obscure. To elucidate these molecular underpinnings, we performed coarse-grained molecular dynamics simulations of HIV-1 virions pinned to the CD4 T cell membrane by different numbers of gp41 trimers. We built realistic cell and viral membranes by mimicking their respective lipid compositions. We found that a single gp41 was inadequate for mediating fusion. Lipid mixing between membranes, indicating the onset of fusion, was efficient when 3 or more gp41 trimers pinned the membranes. The gp41 trimers interacted strongly with many different lipids in the host cell membrane, triggering lipid configurational rearrangements, exchange, and mixing. Simpler membranes, comprising fewer lipid types, displayed strong resistance to fusion, revealing the crucial role of the lipidomes in HIV-1 entry. Performing simulations at different temperatures, we estimated the free energy barrier to lipid mixing, and hence membrane stalk formation, with 4 tethering gp41 trimers to be ~6.2 kcal/mol, a >4-fold reduction over estimates without gp41. Together, these findings present molecular-level, quantitative insights into the early stages of gp41-mediated HIV-1 entry. Preventing the requisite gp41 molecules from tethering the membranes or altering membrane lipid compositions may be potential intervention strategies.SIGNIFICANCEInteractions between viral envelope proteins and host cell surface receptors leading to HIV-1 entry are well studied, however the role of membrane lipids remains obscure, although entry hinges on lipid mixing and the fusion of viral and cell membranes. We performed detailed simulations of HIV-1 and target cell membranes tethered by viral gp41 trimeric proteins to elucidate the proteo-lipidic contributions to viral entry. We found that the cooperative effects of multiple gp41 trimers and natural lipidomes of the membranes facilitate membrane fusion. The functional domains of gp41 altered local lipid concentrations, reduced membrane repulsions, and facilitated inter-membrane lipid mixing. These molecular-level insights offer a glimpse of the cryptic mechanisms underlying HIV-1 entry and suggest new interventions to combat HIV-1 infection.

scholarly journals Caveolin-1 Modulates HIV-1 Envelope-Induced Bystander Apoptosis through gp41

2010 ◽  
Vol 84 (13) ◽  
pp. 6515-6526 ◽  
Author(s):  
Xiao Mei Wang ◽  
Peter E. Nadeau ◽  
Yung-Tsun Lo ◽  
Ayalew Mergia
Keyword(s):  
Lipid Rafts ◽  
Human Peripheral Blood ◽  
Membrane Lipid ◽  
Target Cells ◽  
Signal Pathways ◽  
Caveolin 1 ◽  
Immunodeficiency Virus ◽  
Hiv Envelope ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus (HIV) envelope (Env)-mediated bystander apoptosis is known to cause the progressive, severe, and irreversible loss of CD4+ T cells in HIV-1-infected patients. Env-induced bystander apoptosis has been shown to be gp41 dependent and related to the membrane hemifusion between envelope-expressing cells and target cells. Caveolin-1 (Cav-1), the scaffold protein of specific membrane lipid rafts called caveolae, has been reported to interact with gp41. However, the underlying pathological or physiological meaning of this robust interaction remains unclear. In this report, we examine the interaction of cellular Cav-1 and HIV gp41 within the lipid rafts and show that Cav-1 modulates Env-induced bystander apoptosis through interactions with gp41 in SupT1 cells and CD4+ T lymphocytes isolated from human peripheral blood. Cav-1 significantly suppressed Env-induced membrane hemifusion and caspase-3 activation and augmented Hsp70 upregulation. Moreover, a peptide containing the Cav-1 scaffold domain sequence markedly inhibited bystander apoptosis and apoptotic signal pathways. Our studies shed new light on the potential role of Cav-1 in limiting HIV pathogenesis and the development of a novel therapeutic strategy in treating HIV-1-infected patients.

Targeting Cell Membrane Lipid Rafts by Stoichiometric Functionalization of Gold Nanoparticles with a Sphingolipid-Binding Domain Peptide

2015 ◽  
Vol 4 (6) ◽  
pp. 911-917 ◽  
Author(s):  
David Paramelle ◽  
Daniel Nieves ◽  
Benjamin Brun ◽  
Rachel S. Kraut ◽  
David G. Fernig
Keyword(s):  
Gold Nanoparticles ◽  
Cell Membrane ◽  
Lipid Rafts ◽  
Membrane Lipid ◽  
Binding Domain ◽  
Domain Peptide

scholarly journals Further evidence that paroxysmal nocturnal haemoglobinuria is a disorder of defective cell membrane lipid rafts

2015 ◽  
Vol 19 (9) ◽  
pp. 2193-2201 ◽  
Author(s):  
Mariusz Z. Ratajczak ◽  
Sylwia Borkowska ◽  
Kasia Mierzejewska ◽  
Magda Kucia ◽  
Ewa Mendek-Czajkowska ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Lipid Rafts ◽  
Membrane Lipid ◽  
Paroxysmal Nocturnal Haemoglobinuria

scholarly journals Human Immunodeficiency Virus Type 1 Envelope Glycoproteins That Lack Cytoplasmic Domain Cysteines: Impact on Association with Membrane Lipid Rafts and Incorporation onto Budding Virus Particles

2004 ◽  
Vol 78 (10) ◽  
pp. 5500-5506 ◽  
Author(s):  
Jayanta Bhattacharya ◽  
Paul J. Peters ◽  
Paul R. Clapham
Keyword(s):  
Human Immunodeficiency Virus ◽  
Lipid Rafts ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cytoplasmic Domain ◽  
Membrane Lipid ◽  
Immunodeficiency Virus ◽  
Envelope Trafficking ◽  
Hiv 1

ABSTRACT The human immunodeficiency virus type 1 (HIV-1) envelope comprises a surface gp120 and a transmembrane gp41. The cytoplasmic domain of gp41 contains cysteine residues (C764 and C837) which are targets for palmitoylation and were reported to be required for envelope association with lipid rafts and assembly on budding virions (I. Rousso, M. B. Mixon, B. K. Chen, and P. S. Kim, Proc. Natl. Acad. Sci. USA 97:13523-13525, 2000). Several infectious HIV-1 clones contain envelopes that have no gp41 cytoplasmic cysteines. Since no other gp41 amino acid is a target for palmitoylation, these clones imply that palmitoylation is not essential for envelope trafficking and assembly. Here, we show that HIV-1 envelope mutants that lack gp41 cytoplasmic cysteines are excluded from light lipid rafts. Envelopes that contained residues with bulky hydrophobic side chains instead of cysteines retained their association with heavy rafts and were nearly fully functional for incorporation into virions and infectivity. Substitution of cysteines with alanines or serines eliminated raft association and more severely reduced envelope incorporation onto virions and their infectivity. Nevertheless, the A764/A837 mutant envelope retained nearly 40% infectivity compared to the wild type, even though this envelope was excluded from lipid rafts. Our results demonstrate that gp41 cytoplasmic cysteines that are targets for palmitoylation and are required for envelope trafficking to classical lipid rafts are not essential for HIV-1 replication.

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