Sphingolipids: Modulators of HIV-1 Infection and Pathogenesis

Rawat, Satinder S.; Johnson, Benitra T.; Puri, Anu

doi:10.1007/s10540-005-2894-5

Cited by 36 publications

(37 citation statements)

References 70 publications

(64 reference statements)

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“…One of these domain types, termed rafts, is in a solid-like ordered state [50]. The rafts are present in most mammalian plasma membranes and can serve as platforms for both signaling as well as the entry of pathogens such as viruses, including the HIV [50][51][52][53][54][55]. Also the lipid composition of native HIV membranes resembles raft domains [56].…”

Section: Resultsmentioning

confidence: 99%

Synchrotron SAX and WAX diffraction study of a hydrated very long-chain, dendritic amphiphile+DPPC mixture

Karlovská

Williams

Macri

et al. 2007

Colloids and Surfaces B: Biointerfaces

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The tri-headed anionic dendritic amphiphile, 4-(2-carboxyethyl)-4-[(icosyloxycarbonyl)amino]heptanedioic acid (3CCb20), forms solid-like gel-state mixed micelles with dipalmitoylphosphatidylcholine (DPPC) in excess water at 3CCb20 : DPPC = 0.91 : 1 molar ratio. On heating, these micelles transform into fluid bilayers stacked in the liquid crystalline lamellar L α phase at about 40 °C. This phase transition and the microstructure of 3CCb20 + DPPC aggregates were studied using smalland wide-angle synchrotron X-ray diffraction. The ability of 3CCb20 to solubilize solid-like lipid bilayers could be important in microbiocidal activities of 3CCb20, including in its anti-HIV activity.Keywords: amphiphiles; DPPC; micelles; bilayers; X-ray diffraction; phase transition 3 IntroductionSaturated fatty acids have a long history as microbicides against many pathogens [1][2][3][4][5]. Measurements of inhibitory activities can be problematic because of the very low solubility of saturated fatty acids in aqueous solutions [6]. Furthermore, as the chain length increases to C 18 and beyond, the aqueous solubility becomes immeasurable. Knowing that the compounds completely dissolve in aqueous media enables speculation about how chain length affects microbiological activity. In a homologous series of compounds, antimicrobial activity can show a cut-off effect [7]. Without knowing that the amphiphiles fully dissolve in aqueous media, we cannot conclude that the cut-off effect is due to the "intrinsic" activity of the amphiphiles or due to the decreased solubility of the amphiphile in the microbiological media. The antimicrobial data for 3CCbn show that longer chains (3CCb18-22) are more active than the shorter chains (3CCb14-16). These data contrast with those of saturated fatty acids, where the most active compounds are in the range of C 8 to C 14 [1][2][3][4][5]. A dendritic structure should reduce the absorption of an amphiphile into a cell. The highly branched structure of the head group resembles the dendritic structure of glycolipids that are anchored on the outside of cells. Branching and the triple charge might retard diffusion across membranes. Given the success of very long chain amphiphiles as antimicrobials, there might be a preference for absorption of these amphiphiles on pathogens as opposed to epithelial cells resulting in the reduced irritancy.To understand molecular mechanisms in the biological activities of these compounds, their interactions with different cell constituents must be studied. Several researchers [2,5,19] have proposed that the microbicidal mechanism of action involves fatty acids interacting with membranes. Because of the long alkyl chains, 3CCbn will likely partition into biological membranes. Upon doing so, these amphiphiles will affect the structure and dynamics of the membrane. The phospholipid bilayer comprises the structural matrix of biological membranes. Understanding how amphiphiles interact with a phopholipid bilayer will provide clues to the molecular mechanism of the biological a...

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Section: Resultsmentioning

confidence: 99%

Synchrotron SAX and WAX diffraction study of a hydrated very long-chain, dendritic amphiphile+DPPC mixture

Karlovská

Williams

Macri

et al. 2007

Colloids and Surfaces B: Biointerfaces

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“…CXCR4 is a G-coupled heptahelical receptor that first drew attention as a major coreceptor for the entry of HIV(human immunodeficiency virus) [1]. The CXCR4 and its only characterized chemokine ligand, stromal cell-derived factor-1 (SDF-1), are important in HIV infection [2]. A variety of compounds that target CXCR4 to prevent HIV infection have been developed [2].…”

Section: Introductionmentioning

confidence: 99%

“…The CXCR4 and its only characterized chemokine ligand, stromal cell-derived factor-1 (SDF-1), are important in HIV infection [2]. A variety of compounds that target CXCR4 to prevent HIV infection have been developed [2]. Viral macrophage inflammatory protein (vMIP)-II, a chemokine encoded by human herpes virus 8, displays diverse interactions with both CC and CXC chemokine receptors and inhibits HIV-1 entry mediated through CCR3, CCR5, and CXCR4 [3].…”

Section: Introductionmentioning

confidence: 99%

Anti-HIV Effect of Liposomes Bearing CXCR4 Receptor Antagonist N15P

Yu-hong¹,

Sun²,

Li³

et al. 2013

Trop. J. Pharm Res

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“…It has been hypothesized that recruitment of receptors at the plasma membrane microdomains enriched in sphingolipids and cholesterol (rafts) regulates initial interactions necessary for productive infection [20,21,31,32]. However, the notion that plasma membrane rafts serve as portals for HIV-1 entry has been challenged recently [23,25,36], and, therefore, an understanding of plasma membrane micro-environment at the site of virus-receptor interactions warrants further investigation.…”

Section: Introductionmentioning

confidence: 99%

Restricted lateral mobility of plasma membrane CD4 impairs HIV-1 envelope glycoprotein mediated fusion

Rawat¹,

Zimmerman²,

Johnson³

et al. 2008

Molecular Membrane Biology

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We investigated the effect of receptor mobility on HIV-1 envelope glycoprotein (Env)-triggered fusion using B16 mouse melanoma cells that are engineered to express CD4 and CXCR4 or CCR5. These engineered cells are resistant to fusion mediated CD4-dependent HIV-1 envelope glycoprotein. Receptor mobility was measured by fluorescence recovery after photobleaching (FRAP) using either fluorescently-labeled antibodies or transient expression of GFP-tagged receptors in the cells. No significant differences between B16 and NIH3T3 (fusion-permissive) cells were seen in lateral mobility of CCR5 or lipid probes. By contrast CD4 mobility in B16 cells was about seven-fold reduced compared to its mobility in fusion-permissive NIH3T3 cells. However, a CD4 mutant (RA5) that localizes to non-raft membrane microdomains exhibited a three-fold increased mobility in B16 cells as compared with WT-CD4. Interestingly, the B16 cells expressing the RA5 mutant (but not the wild type CD4) and coreceptors supported HIV-1 Envmediated fusion. Our data demonstrate that the lateral mobility of CD4 is an important determinant of HIV-1 fusion/entry. KeywordsCD4 receptor localization in the plasma membrane; Receptor mobility restriction and HIV-1 fusion

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Sphingolipids: Modulators of HIV-1 Infection and Pathogenesis

Cited by 36 publications

References 70 publications

Synchrotron SAX and WAX diffraction study of a hydrated very long-chain, dendritic amphiphile+DPPC mixture

Synchrotron SAX and WAX diffraction study of a hydrated very long-chain, dendritic amphiphile+DPPC mixture

Anti-HIV Effect of Liposomes Bearing CXCR4 Receptor Antagonist N15P

Restricted lateral mobility of plasma membrane CD4 impairs HIV-1 envelope glycoprotein mediated fusion

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