The Fusion Glycoprotein Shell of Semliki Forest Virus

Lescar, Julien; Roussel, Alain; Wien, M.W.; Navaza, Jorge; Fuller, Stephen D.; Wengler, Gerd; Rey, F.A.

doi:10.1016/s0092-8674(01)00303-8

Cited by 461 publications

(159 citation statements)

References 45 publications

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“…Studies with Semliki Forest virus have demonstrated that the low pH environment of the endosome leads to a dissociation of the E1/E2 heterodimer and a concomitant trimerization of the E1 subunits (6,7,10). An important consequence of the conformational change is the exposure and outward movement of fusion peptides.…”

Section: Fusion Of Sindbis Virus With Erythrocyte Ghosts After Virus mentioning

confidence: 99%

Hydrostatic Pressure Induces the Fusion-active State of Enveloped Viruses

Gaspar¹,

Silva²,

Gomes³

et al. 2002

Journal of Biological Chemistry

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Enveloped animal viruses must undergo membrane fusion to deliver their genome into the host cell. We demonstrate that high pressure inactivates two membrane-enveloped viruses, influenza and Sindbis, by trapping the particles in a fusion-intermediate state. The pressure-induced conformational changes in Sindbis and influenza viruses were followed using intrinsic and extrinsic fluorescence spectroscopy, circular dichroism, and fusion, plaque, and hemagglutination assays. Influenza virus subjected to pressure exposes hydrophobic domains as determined by tryptophan fluorescence and by the binding of bis-8-anilino-1-naphthalenesulfonate, a well established marker of the fusogenic state in influenza virus. Pressure also produced an increase in the fusion activity at neutral pH as monitored by fluorescence resonance energy transfer using lipid vesicles labeled with fluorescence probes. Sindbis virus also underwent conformational changes induced by pressure similar to those in influenza virus, and the increase in fusion activity was followed by pyrene excimer fluorescence of the metabolically labeled virus particles. Overall we show that pressure elicits subtle changes in the whole structure of the enveloped viruses triggering a conformational change that is similar to the change triggered by low pH. Our data strengthen the hypothesis that the native conformation of fusion proteins is metastable, and a cycle of pressure leads to a final state, the fusion-active state, of smaller volume.Enveloped viruses utilize regulated membrane fusion to introduce their genomes in the cytoplasm of the host cell. The fusion is mediated by surface envelope proteins of the virus in response to a trigger (1, 2). Once triggered, the fusion process leads to a conformational change that promotes the interaction of a specific sequence (fusion peptide) with the target membrane and initiates membrane fusion. Membrane fusion is crucial in other biological functions such as myotube formation, fertilization, and trafficking of endocytic and exocytic vesicles within eukaryotic cells (1, 3). Many enveloped animal viruses have been studied as models for understanding the mechanism of membrane fusion. While the fusion proteins of many viruses reveal significant similarity in their putative fusogenic conformation, such as those of influenza virus (hemagglutinin HA2), 1 human immunodeficiency virus (gp41 protein), Moloney murine leukemia virus (TM protein), and Ebola virus (GP2 protein) (4), the events of membrane fusion for other virus families (e.g. Flaviviridae and Togaviridae) are beginning to be understood. Alphavirus and the flavivirus fusion proteins appear to have evolved from a common ancestor (5) and possess a similar new class of membrane fusion proteins that do not form coiledcoils (6 -8).Sindbis and influenza are enveloped viruses that first enter a cell by endocytosis and then fuse with the cellular membrane in response to acidic conditions. Sindbis virus is the prototype of the Alphavirus genus, Togaviridae family. The Alphavirus spike is...

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Section: Fusion Of Sindbis Virus With Erythrocyte Ghosts After Virus mentioning

confidence: 99%

Hydrostatic Pressure Induces the Fusion-active State of Enveloped Viruses

Gaspar¹,

Silva²,

Gomes³

et al. 2002

Journal of Biological Chemistry

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“…They are type I membrane glycoproteins that fold into trimers and contain a protease cleavage site, a fusion peptide and at least two heptad repeat regions, one of which (here designated as HR1) is located downstream and in the vicinity of the fusion peptide, whereas the other (HR2) usually occurs adjacent to the transmembrane domain (3). The fusion proteins acquire a metastable state upon cleavage by cellular proteases.…”

mentioning

confidence: 99%

Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition using spike protein heptad repeat-derived peptides

Bosch

Martina

Zee

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

370

432

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The coronavirus SARS-CoV is the primary cause of the life-threatening severe acute respiratory syndrome (SARS). With the aim of developing therapeutic agents, we have tested peptides derived from the membrane-proximal (HR2) and membrane-distal (HR1) heptad repeat region of the spike protein as inhibitors of SARS-CoV infection of Vero cells. It appeared that HR2 peptides, but not HR1 peptides, were inhibitory. Their efficacy was, however, significantly lower than that of corresponding HR2 peptides of the murine coronavirus mouse hepatitis virus (MHV) in inhibiting MHV infection. Biochemical and electron microscopical analyses showed that, when mixed, SARS-CoV HR1 and HR2 peptides assemble into a six-helix bundle consisting of HR1 as a central triple-stranded coiled coil in association with three HR2 ␣-helices oriented in an antiparallel manner. The stability of this complex, as measured by its resistance to heat dissociation, appeared to be much lower than that of the corresponding MHV complex, which may explain the different inhibitory potencies of the HR2 peptides. Analogous to other class I viral fusion proteins, the six-helix complex supposedly represents a postfusion conformation that is formed after insertion of the fusion peptide, proposed here for coronaviruses to be located immediately upstream of HR1, into the target membrane. The resulting close apposition of fusion peptide and spike transmembrane domain facilitates membrane fusion. The inhibitory potency of the SARS-CoV HR2-peptides provides an attractive basis for the development of a therapeutic drug for SARS.

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“…Because different flaviviruses (i.e., TBE, dengue, yellow fever, West Nile, Japanese encephalitis viruses, and others) display Ϸ40% amino acid conservation in their envelope protein (6), the overall fold and the arrangement of domains of these proteins is expected to be similar. This prediction has been further substantiated by the finding that the fusion glycoprotein E1 of Semliki Forest virus (SFV), an alphavirus belonging to the togaviridae family of viruses, displays structural homology, with the same fold and domain arrangement despite the absence of any noticeable sequence similarity (8). In contrast to flaviviruses, the membrane fusion and the receptor-binding functions of alphaviruses are carried out by two different glycoproteins (9).…”

mentioning

confidence: 99%

“…Now, Modis et al (4) find that most of the side chains identified by these mutations line the pocket, which opens as a result of the transfer of a ␤-hairpin from one ␤-sheet to a neighboring, apposed ␤-sheet. Flexibility in the hinge region of the fusion protein is likely to be a hallmark of class II enveloped viruses, because different conformations about this area were also identified in the case of the SFV E1 glycoprotein (8). This feature is very likely to be involved in the conformational change that is necessary to trigger membrane fusion.…”

mentioning

confidence: 99%

The Fusion Glycoprotein Shell of Semliki Forest Virus

Cited by 461 publications

References 45 publications

Hydrostatic Pressure Induces the Fusion-active State of Enveloped Viruses

Hydrostatic Pressure Induces the Fusion-active State of Enveloped Viruses

Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition using spike protein heptad repeat-derived peptides

Dengue virus envelope glycoprotein structure: New insight into its interactions during viral entry

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