Liposomes as Target Membranes in the Study of Virus Receptor Interaction and Membrane Fusion

Smit, Jolanda M.; Waarts, Barry-Lee; Bittman, Robert; Wilschut, Jan

doi:10.1016/s0076-6879(03)72022-9

Cited by 16 publications

(31 citation statements)

References 29 publications

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“…We utilized a model liposome fusion assay with pyrene-labeled virus [37], [38] to confirm these results. Pyrene-labeled CHIKV was pre-incubated with different concentrations of MAb, mixed with liposomes at 37°C, and fusion was triggered by addition of a low-pH buffer [37].…”

Section: Resultsmentioning

confidence: 99%

Development of a Highly Protective Combination Monoclonal Antibody Therapy against Chikungunya Virus

Pal

Dowd

Brien³

et al. 2013

PLoS Pathog

244

368

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Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes global epidemics of a debilitating polyarthritis in humans. As there is a pressing need for the development of therapeutic agents, we screened 230 new mouse anti-CHIKV monoclonal antibodies (MAbs) for their ability to inhibit infection of all three CHIKV genotypes. Four of 36 neutralizing MAbs (CHK-102, CHK-152, CHK-166, and CHK-263) provided complete protection against lethality as prophylaxis in highly susceptible immunocompromised mice lacking the type I IFN receptor (Ifnar−/−) and mapped to distinct epitopes on the E1 and E2 structural proteins. CHK-152, the most protective MAb, was humanized, shown to block viral fusion, and require Fc effector function for optimal activity in vivo. In post-exposure therapeutic trials, administration of a single dose of a combination of two neutralizing MAbs (CHK-102+CHK-152 or CHK-166+CHK-152) limited the development of resistance and protected immunocompromised mice against disease when given 24 to 36 hours before CHIKV-induced death. Selected pairs of highly neutralizing MAbs may be a promising treatment option for CHIKV in humans.

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Section: Resultsmentioning

confidence: 99%

Development of a Highly Protective Combination Monoclonal Antibody Therapy against Chikungunya Virus

Pal

Dowd

Brien³

et al. 2013

PLoS Pathog

244

368

View full text Add to dashboard Cite

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“…This was determined in a direct binding assay. Radioactively labeled SFV, prepared by infection of BHK-21 cells in the presence of [ 35 S]methionine as described before (3,25,33,37), was exposed to pH 5.5 in the absence of liposomes for 2 min. Subsequently, liposomes were added, and the incubation was continued for 3 min, after which the mixture was neutralized for analysis.…”

Section: Vol 79 2005 Notes 7943mentioning

confidence: 99%

“…As a control, a mixture of virus and liposomes was exposed to low pH for 5 min and subsequently neutralized for analysis. Binding of the virus to the liposomes was assessed by flotation analysis on a sucrose density gradient as described before (3,25,33,37). Figure 2 shows the results.…”

Section: Vol 79 2005 Notes 7943mentioning

confidence: 99%

“…Fusion of SFV with liposomes was measured by using pyrene-labeled virus, essentially as described before (3,25,33,37). Briefly, SFV was grown on baby hamster kidney cells (BHK-21) cultured beforehand in the presence of 1-pyrenehexadecanoic acid (Molecular Probes, Leiden, The Netherlands).…”

mentioning

confidence: 99%

“…There was no detectable fusion when liposomes were added 80 s or longer after the initial acidification of the virus. (33). The fusion scale was set such that the initial excimer fluorescence at 480 nm represented 0% fusion and the residual fluorescence, after addition of the detergent octaethyleneglycol-monododecyl ether to a final concentration of 10 mM (representing infinite dilution of the fluorophore), corresponded to 100% fusion.…”

mentioning

confidence: 99%

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Reversible Acid-Induced Inactivation of the Membrane Fusion Protein of Semliki Forest Virus

Waarts

Smit

Aneke

et al. 2005

J Virol

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Previously, it has been shown that the exposure of Semliki Forest virus (SFV) to a mildly acidic environment induces a rapid and complete loss of the ability of the virus to bind and fuse to target membranes added subsequently. In the present study, incubation of SFV at low pH followed by a specific reneutralization step resulted in a partial reversion of this loss of viral fusion capacity, as assessed in a liposomal model system. Also, the ability of the viral E1 fusion protein to undergo liposome-stimulated trimerization was restored. Furthermore, acid-treated and neutralized SFV largely retained infectivity. Exposure of SFV to low pH induced dissociation of the E1/E2 heterodimer, which was not reversed upon neutralization. It is concluded that the SFV E1 fusion protein, after acid-induced dissociation from E2, rapidly adopts an intermediate, nontrimeric conformation in which it is no longer able to interact with target membrane lipids. Neutralization restores the ability of E1 to interact with membranes. This interaction, however, remains strictly dependent on low pH.Semliki Forest virus (SFV) is an enveloped positive-strand RNA virus belonging to the genus Alphavirus of the family Togaviridae. It is well established that SFV enters its host cell through receptor-mediated endocytosis via the clathrin-coated pit pathway, fusing subsequently from within acidic endosomes (14,20). Through this fusion reaction, the viral genome gains access to the host cell cytosol and initiates the infection process. The low-pH-induced fusion process of SFV has been studied extensively in cell-free model systems involving liposomes as receptor-free target membranes (3,16,25,37,39,40). These studies have demonstrated that low pH is the sole trigger for membrane fusion of SFV and that receptor interaction is not required for the induction of the process. In addition, these studies have revealed a striking dependence of SFV fusion on the presence of both cholesterol (Chol) and sphingolipids in the target membrane (3,5,15,16,24,25,36,37,39,40). Studies conducted with another prototype alphavirus, Sindbis virus, have led to similar conclusions (30,31,32,34).Membrane fusion of alphaviruses is mediated by the E1 component of the heterodimeric E1/E2 envelope glycoprotein (6, 37). Recent X-ray crystallographic analyses of the structure of the alphavirus membrane fusion protein (19) have revealed that it has striking similarities with the structure of membrane fusion protein E of flaviviruses (22, 27) and major differences with the structure of the fusion protein hemagglutinin (HA) of influenza virus (29, 41) and other HA-related viral membrane fusion proteins. This has led to the definition of class I (HA and related proteins) and class II (alphavirus and flavivirus proteins) viral fusion proteins. Interestingly, very recent structural analyses of the postfusion structures of two class II proteins (2, 10, 11, 23) suggest that there may well be mechanistic similarities between the fusion reactions mediated by the structurally distinct clas...

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Nano‐therapeutic strategies to target coronavirus

Rauf

Tasleem

Bhise

et al. 2021

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The coronaviruses have caused severe acute respiratory syndrome (SARS), the Middle East respiratory syndrome (MERS), and the more recent coronavirus pneumonia . The global COVID-19 pandemic requires urgent action to develop anti-virals, new therapeutics, and vaccines. In this review, we discuss potential therapeutics including human recombinant ACE2 soluble, inflammatory cytokine inhibitors, and direct anti-viral agents such as remdesivir and favipiravir, to limit their fatality. We also discuss the structure of the SARS-CoV-2, which is crucial to the timely development of therapeutics, and previous attempts to generate vaccines against SARS-CoV and MERS-CoV. Finally, we provide an overview of the role of nanotechnology in the development of therapeutics as well as in the diagnosis of the infection. This information is key for computational modeling and nanomedicine-based new therapeutics by counteracting the variable proteins in the virus. Further, we also try to effectively share the latest information about many different aspects of COVID-19 vaccine developments and possible management to further scientific endeavors.

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Liposomes as Target Membranes in the Study of Virus Receptor Interaction and Membrane Fusion

Cited by 16 publications

References 29 publications

Development of a Highly Protective Combination Monoclonal Antibody Therapy against Chikungunya Virus

Development of a Highly Protective Combination Monoclonal Antibody Therapy against Chikungunya Virus

Reversible Acid-Induced Inactivation of the Membrane Fusion Protein of Semliki Forest Virus

Nano‐therapeutic strategies to target coronavirus

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