Three-Dimensional Structure of Herpes Simplex Virus from Cryo-Electron Tomography

Grünewald, Kay; Desai, Prashant; Winkler, Dennis C.; Heymann, J. Bernard; Belnap, David M.; Baumeister, Wolfgang; Steven, Alasdair C.

doi:10.1126/science.1090284

Cited by 518 publications

(483 citation statements)

References 24 publications

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“…Indeed, it is known that proteins, such as Fc gamma receptors, can be indirectly raft associated through their affinity for other raft-associated proteins (16). Importantly, since lipid raft formation and protein association with lipid rafts occur in the Golgi complex (14), such a putative glycoprotein and tegument protein concentrating function of lipid rafts may also be significant for efficient alphaherpesvirus budding and particle formation, as has been hypothesized recently (17,23,26). In this context, it is interesting that lipid rafts have recently been shown to serve as budding platforms for several enveloped viruses, such as human immunodeficiency virus, Ebola virus, influenza virus, and measles virus (1,28,35,36,40), and that such lipid raft-mediated budding has been hypothesized to explain pseudotyping of different viruses, including HSV (37).…”

Section: Vol 78 2004 Lipid Raft Association Of Prv Glycoproteins 5285mentioning

confidence: 89%

“…In this context, it is interesting that lipid rafts have recently been shown to serve as budding platforms for several enveloped viruses, such as human immunodeficiency virus, Ebola virus, influenza virus, and measles virus (1,28,35,36,40), and that such lipid raft-mediated budding has been hypothesized to explain pseudotyping of different viruses, including HSV (37). Further, the viral glycoprotein distribution in the HSV virion envelope has been shown to be nonrandom, which has been hypothesized to be caused by association of viral glycoproteins with lipid rafts (17). In addition, we have found that, like for human immunodeficiency virus (15,27), cholesterol in the PRV envelope is required for infectivity, since depletion of cholesterol from PRV preparations by using 10 mM MCD completely abolished PRV's ability to successfully infect susceptible cells (data not shown).…”

Section: Vol 78 2004 Lipid Raft Association Of Prv Glycoproteins 5285mentioning

confidence: 99%

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Copatching and Lipid Raft Association of Different Viral Glycoproteins Expressed on the Surfaces of Pseudorabies Virus-Infected Cells

Favoreel

Mettenleiter²,

Nauwynck³

2004

J Virol

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Pseudorabies virus (PRV) is a swine alphaherpesvirus that is closely related to human herpes simplex virus (HSV). Both PRV and HSV express a variety of viral envelope glycoproteins in the plasma membranes of infected cells. Here we show that at least four major PRV glycoproteins (gB, gC, gD, and gE) in the plasma membrane of infected swine kidney cells and monocytes seem to be linked, since monospecific antibody-induced patching of any one of these proteins results in copatching of the others. Further, for all four PRV glycoproteins, monospecific antibody-induced patches were enriched in GM1, a typical marker of lipid raft microdomains, but were excluded for transferrin receptor, a nonraft marker, suggesting that these viral proteins may associate with lipid rafts. However, only gB and, to a lesser extent, gE were found in lipid raft fractions by using detergent floatation assays, indicating that gC and gD do not show strong lipid raft association. Addition of methyl-␤-cyclodextrin (MCD), a cholesterol-depleting agent that is commonly used to disrupt lipid rafts, only slightly reduced copatching efficiency between the different viral proteins, indicating that other factors, perhaps tegument-glycoprotein interactions, may be important for the observed copatching events. On the other hand, MCD strongly reduced polarization of the antibody-induced viral glycoprotein patches to a cap structure, a gE-dependent process that has been described for specific PRV-and HSV-infected cells. Therefore, we hypothesize that efficient gE-mediated capping of antibody-antigen patches may require the lipid raft-associated signal transduction machinery.

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Section: Vol 78 2004 Lipid Raft Association Of Prv Glycoproteins 5285mentioning

confidence: 89%

Section: Vol 78 2004 Lipid Raft Association Of Prv Glycoproteins 5285mentioning

confidence: 99%

Copatching and Lipid Raft Association of Different Viral Glycoproteins Expressed on the Surfaces of Pseudorabies Virus-Infected Cells

Favoreel

Mettenleiter²,

Nauwynck³

2004

J Virol

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“…Using the conservative 0.5 criterion, the resolution of the complex was estimated to be 3.0 nm. One alternative criterion, which infers the correlation between a perfect reference and a reconstruction from the full data set, as proposed in (Grunewald et al, 2003;Rosenthal and Henderson, 2003) gives a resolution of 2.6 nm. Another alternative, accepting the 1/2 bit criterion formulated in (van Heel and Schatz, 2005), gives an estimate of 2.7 nm.…”

Section: Reconstruction Of Poliovirus-receptor-liposome Complexmentioning

confidence: 99%

“…Initially, this approach was applied to determine the structures of macromolecular complexes in vitro (Beck et al, 2004;Cardone et al, 2007;Chang et al, 2007;Cheng et al, 2007;Deng et al, 2007;Grunewald et al, 2003;Harris et al, 2006;Nicastro et al, 2005;Nicastro et al, 2006;Nickell et al, 2007;Zhu et al, 2006). Perhaps more excitingly, the approach has begun to be used to study macromolecular complexes within the context of intact cells.…”

Section: Introductionmentioning

confidence: 99%

Single particle cryoelectron tomography characterization of the structure and structural variability of poliovirus–receptor–membrane complex at 30 Å resolution

Bostina

Bubeck

Schwartz

et al. 2007

Journal of Structural Biology

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As a long-term goal we want to use cryoelectron tomography to understand how non-enveloped viruses, such as picornaviruses, enter cells and translocate their genomes across membranes. To this end, we developed new image-processing tools using an in vitro system to model viral interactions with membranes. The complex of poliovirus with its membrane-bound receptors was reconstructed by averaging multiple sub-tomograms, thereby producing three-dimensional maps of surprisingly high resolution (30Å). Recognizable images of the complex could be produced by averaging as few as 20 copies. Additionally, model-free reconstructions of free poliovirus particles, clearly showing the major surface features, could be calculated from 60 virions. All calculations were designed to avoid artifacts caused by missing information typical for tomographic data ("missing wedge"). To investigate structural and conformational variability we applied a principal component analysis classification to specific regions. We show that the missing wedge causes a bias in classification, and that this bias can be minimized by supplementation with data from the Fourier transform of the averaged structure. After classifying images of the receptor into groups with high similarity, we were able to see differences in receptor density consistent with the known variability in receptor glycosylation.

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“…The virion structure is of interest not only in the context of virus assembly but also in light of the possibility that pleiomorphic variations may correlate with infectivity and/or pathogenicity. As a step toward addressing these questions, we have used cryoelectron tomography, a technique capable of rendering the 3D structures of individual macromolecular particles in their native states (19)(20)(21)(22)(23)(24)(25), to visualize influenza virions of the type A eggadapted X-31 strain (26).…”

mentioning

confidence: 99%

Influenza virus pleiomorphy characterized by cryoelectron tomography

Harris

Cardone

Winkler

et al. 2006

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

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449

542

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Influenza virus remains a global health threat, with millions of infections annually and the impending threat that a strain of avian influenza may develop into a human pandemic. Despite its importance as a pathogen, little is known about the virus structure, in part because of its intrinsic structural variability (pleiomorphy): the primary distinction is between spherical and elongated particles, but both vary in size. Pleiomorphy has thwarted structural analysis by image reconstruction of electron micrographs based on averaging many identical particles. In this study, we used cryoelectron tomography to visualize the 3D structures of 110 individual virions of the X-31 (H3N2) strain of influenza A. The tomograms distinguish two kinds of glycoprotein spikes [hemagglutinin (HA) and neuraminidase (NA)] in the viral envelope, resolve the matrix protein layer lining the envelope, and depict internal configurations of ribonucleoprotein (RNP) complexes. They also reveal the stems that link the glycoprotein ectodomains to the membrane and interactions among the glycoproteins, the matrix, and the RNPs that presumably control the budding of nascent virions from host cells. Five classes of virions, four spherical and one elongated, are distinguished by features of their matrix layer and RNP organization. Some virions have substantial gaps in their matrix layer (''molecular fontanels''), and others appear to lack a matrix layer entirely, suggesting the existence of an alternative budding pathway in which matrix protein is minimally involved.envelope glycoproteins ͉ matrix protein ͉ ribonucleoprotein particles ͉ virus assembly ͉ virus structure

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Three-Dimensional Structure of Herpes Simplex Virus from Cryo-Electron Tomography

Cited by 518 publications

References 24 publications

Copatching and Lipid Raft Association of Different Viral Glycoproteins Expressed on the Surfaces of Pseudorabies Virus-Infected Cells

Copatching and Lipid Raft Association of Different Viral Glycoproteins Expressed on the Surfaces of Pseudorabies Virus-Infected Cells

Single particle cryoelectron tomography characterization of the structure and structural variability of poliovirus–receptor–membrane complex at 30 Å resolution

Influenza virus pleiomorphy characterized by cryoelectron tomography

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