Structures of capsid and capsid-associated tegument complex inside the Epstein-Barr virus.

Amino Acid Sequence Capsid / chemistry Capsid Proteins / chemistry Cryoelectron Microscopy Epstein-Barr Virus Infections / virology Herpesvirus 4, Human / physiology Humans Imaging, Three-Dimensional Models, Molecular Protein Subunits Structure-Activity Relationship Virion / ultrastructure Virus Assembly

Journal

Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869

Informations de publication

Date de publication:
10 2020
Historique:
received: 02 01 2020
accepted: 19 06 2020
pubmed: 29 7 2020
medline: 22 12 2020
entrez: 29 7 2020
Statut: ppublish

Résumé

As the first discovered human cancer virus, Epstein-Barr virus (EBV) causes Burkitt's lymphoma and nasopharyngeal carcinoma. Isolating virions for determining high-resolution structures has been hindered by latency-a hallmark of EBV infection-and atomic structures are thus available only for recombinantly expressed EBV proteins. In the present study, by symmetry relaxation and subparticle reconstruction, we have determined near-atomic-resolution structures of the EBV capsid with an asymmetrically attached DNA-translocating portal and capsid-associated tegument complexes from cryogenic electron microscopy images of just 2,048 EBV virions obtained by chemical induction. The resulting atomic models reveal structural plasticity among the 20 conformers of the major capsid protein, 2 conformers of the small capsid protein (SCP), 4 conformers of the triplex monomer proteins and 2 conformers of the triplex dimer proteins. Plasticity reaches the greatest level at the capsid-tegument interfaces involving SCP and capsid-associated tegument complexes (CATC): SCPs crown pentons/hexons and mediate tegument protein binding, and CATCs bind and rotate all five periportal triplexes, but notably only about one peri-penton triplex. These results offer insights into the EBV capsid assembly and a mechanism for recruiting cell-regulating factors into the tegument compartment as 'cargoes', and should inform future anti-EBV strategies.

Identifiants

DOI: 10.1038/s41564-020-0758-1 PMID: 32719506 PMC: PMC7546529
pubmed: 32719506
doi: 10.1038/s41564-020-0758-1
pii: 10.1038/s41564-020-0758-1
pmc: PMC7546529
mid: NIHMS1630658
doi:

Substances chimiques

Capsid Proteins 0
Protein Subunits 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

1285-1298

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI094386
Pays : United States
Organisme : NIH HHS
ID : S10 OD018111
Pays : United States
Organisme : NIGMS NIH HHS
ID : U24 GM116792
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE025567
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR023057
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE028583
Pays : United States

Références

Epstein, M. A., Achong, B. G. & Barr, Y. M. Virus particles in cultured lymphoblasts from Burkitt’s lymphoma. Lancet 283, 702–703 (1964).
Salahuddin, S. Z. et al. Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science 234, 596–601 (1986).
pubmed: 2876520
Andersson, J. P. Clinical aspects on Epstein–Barr virus infection. Scand. J. Infect. Dis. Suppl. 80, 94–104 (1991).
pubmed: 1666450
Fugl, A. & Andersen, C. L. Epstein–Barr virus and its association with disease—a review of relevance to general practice. BMC Fam. Pract. 20, 62 (2019).
pubmed: 31088382 pmcid: 6518816
Bochkarev, A. et al. Crystal structure of the DNA-binding domain of the Epstein–Barr virus origin-binding protein EBNA1. Cell 83, 39–46 (1995).
pubmed: 7553871
Huang, H. et al. Structural basis underlying viral hijacking of a histone chaperone complex. Nat. Commun. 7, 12707 (2016).
pubmed: 27581705 pmcid: 5025803
Mullen, M. M., Haan, K. M., Longnecker, R. & Jardetzky, T. S. Structure of the Epstein–Barr virus gp42 protein bound to the MHC class II receptor HLA-DR1. Mol. Cell 9, 375–385 (2002).
pubmed: 11864610
Matsuura, H., Kirschner, A. N., Longnecker, R. & Jardetzky, T. S. Crystal structure of the Epstein–Barr virus (EBV) glycoprotein H/glycoprotein L (gH/gL) complex. Proc. Natl Acad. Sci. USA 107, 22641–22646 (2010).
pubmed: 21149717
Machón, C. et al. Atomic structure of the Epstein–Barr virus portal. Nat. Commun. 10, 3891 (2019).
pubmed: 31467275 pmcid: 6715670
Germi, R. et al. Three-dimensional structure of the Epstein–Barr virus capsid. J. Gen. Virol. 93, 1769–1773 (2012).
pubmed: 22592267
Dai, X. et al. Structure and mutagenesis reveal essential capsid protein interactions for KSHV replication. Nature 553, 521–525 (2018).
pubmed: 29342139 pmcid: 6039102
Dai, X. & Zhou, Z. H. Structure of the herpes simplex virus 1 capsid with associated tegument protein complexes. Science 360, eaao7298 (2018).
Wang, J. et al. Structure of the herpes simplex virus type 2 C-capsid with capsid-vertex-specific component. Nat. Commun. 9, 3668 (2018).
pubmed: 30201968 pmcid: 6131487
Yuan, S. et al. Cryo-EM structure of a herpesvirus capsid at 3.1 Å. Science 360, eaao7283 (2018).
Yu, X., Jih, J., Jiang, J. & Zhou, Z. H. Atomic structure of the human cytomegalovirus capsid with its securing tegument layer of pp150. Science 356, eaam6892 (2017).
pubmed: 28663444 pmcid: 5715728
Liu, W. et al. Atomic structures and deletion mutant reveal different capsid-binding patterns and functional significance of tegument protein pp150 in murine and human cytomegaloviruses with implications for therapeutic development. PLoS Pathog. 15, e1007615 (2019).
pubmed: 30779794 pmcid: 6396938
Zhang, Y. et al. Atomic structure of the human herpesvirus 6B capsid and capsid-associated tegument complexes. Nat. Commun. 10, 5346 (2019).
pubmed: 31767868 pmcid: 6877594
Gong, D. et al. DNA-packing portal and capsid-associated tegument complexes in the tumor herpesvirus KSHV. Cell 178, 1329–1343 (2019).
pubmed: 31447177 pmcid: 6753055
Liu, Y. T., Jih, J., Dai, X., Bi, G. Q. & Zhou, Z. H. Cryo-EM structures of herpes simplex virus type 1 portal vertex and packaged genome. Nature 570, 257–261 (2019).
pubmed: 31142842 pmcid: 6732574
Fokine, A. et al. Structural and functional similarities between the capsid proteins of bacteriophages T4 and HK97 point to a common ancestry. Proc. Natl Acad. Sci. USA 102, 7163–7168 (2005).
pubmed: 15878991
Zhang, X. et al. A new topology of the HK97-like fold revealed in Bordetella bacteriophage by cryoEM at 3.5 Å resolution. eLife 2, e01299 (2013).
pubmed: 24347545 pmcid: 3863775
Scrima, N. et al. Insights into herpesvirus tegument organization from structural analyses of the 970 central residues of HSV-1 UL36 protein. J. Biol. Chem. 290, 8820–8833 (2015).
pubmed: 25678705 pmcid: 4423674
Wang, W. et al. Atomic structures of varicella-zoster virus capsids. Nat. Microbiol. (in the press).
Liu, Y.-T. et al. A pUL25 dimer interfaces the pseudorabies virus capsid and tegument. J. Gen. Virol. 98, 2837–2849 (2017).
pubmed: 29035172 pmcid: 5718256
McElwee, M., Vijayakrishnan, S., Rixon, F. & Bhella, D. Structure of the herpes simplex virus portal-vertex. PLoS Biol. 16, e2006191 (2018).
pubmed: 29924793 pmcid: 6028144
Crick, F. H. C. & Watson, J. D. Structure of small viruses. Nature 177, 473–475 (1956).
pubmed: 13309339
Caspar, D. L. & Klug, A. Physical principles in the construction of regular viruses. Cold Spring Harb. Symp. Quant. Biol. 27, 1–24 (1962).
pubmed: 14019094
Harrison, S. C., Olson, A. J., Schutt, C. E., Winkler, F. K. & Bricogne, G. Tomato bushy stunt virus at 2.9 Å resolution. Nature 276, 368–373 (1978).
pubmed: 19711552
Abad-Zapatero, C. et al. Structure of southern bean mosaic virus at 2.8 Å resolution. Nature 286, 33–39 (1980).
pubmed: 19711553
Liddington, R. C. et al. Structure of simian virus 40 at 3.8-Å resolution. Nature 354, 278–284 (1991).
pubmed: 1659663
Vogel, R. H., Provencher, S. W., von Bonsdorff, C. H., Adrian, M. & Dubochet, J. Envelope structure of Semliki Forest virus reconstructed from cryo-electron micrographs. Nature 320, 533–535 (1986).
pubmed: 3960136
Liu, X. & Cohen, J. I. Epstein–Barr virus (EBV) tegument protein BGLF2 promotes EBV reactivation through activation of the p38 mitogen-activated protein kinase. J. Virol. 90, 1129–1138 (2016).
pubmed: 26559845
Tsai, K., Thikmyanova, N., Wojcechowskyj, J. A., Delecluse, H. J. & Lieberman, P. M. EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription. PLoS Pathog. 7, e1002376 (2011).
pubmed: 22102817 pmcid: 3213115
Shumilov, A. et al. Epstein–Barr virus particles induce centrosome amplification and chromosomal instability. Nat. Commun. 8, 14257 (2017).
pubmed: 28186092 pmcid: 5309802
Whitehurst, C. B. et al. Knockout of Epstein–Barr virus BPLF1 retards B-cell transformation and lymphoma formation in humanized mice. mBio 6, e01574-15 (2015).
pubmed: 26489865 pmcid: 4620474
Rozen, R., Sathish, N., Li, Y. & Yuan, Y. Virion-wide protein interactions of Kaposi’s sarcoma-associated herpesvirus. J. Virol. 82, 4742–4750 (2008).
pubmed: 18321973 pmcid: 2346726
Crowther, R. A., Amos, L. A., Finch, J. T., De Rosier, D. J. & Klug, A. Three dimensional reconstructions of spherical viruses by fourier synthesis from electron micrographs. Nature 226, 421–425 (1970).
pubmed: 4314822
Weibel, R. E. et al. Live attenuated varicella virus vaccine. Efficacy trial in healthy children. N. Engl. J. Med. 310, 1409–1415 (1984).
pubmed: 6325909
Gong, D. et al. Virus-Like Vesicles of Kaposi’s Sarcoma-Associated Herpesvirus Activate Lytic Replication by Triggering Differentiation Signaling. J. Virol. 91, 17 (2017).
Mastronarde, D. N. Automated electron microscope tomography using robust prediction of specimen movements. J. Struct. Biol. 152, 36–51 (2005).
pubmed: 16182563
Jin, L. et al. Applications of direct detection device in transmission electron microscopy. J. Struct. Biol. 161, 352–358 (2008).
pubmed: 18054249
Yonekura, K., Braunfeld, M. B., Maki-Yonekura, S. & Agard, D. A. Electron energy filtering significantly improves amplitude contrast of frozen-hydrated protein at 300 kV. J. Struct. Biol. 156, 524–536 (2006).
pubmed: 16987672
Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331–332 (2017).
pubmed: 28250466 pmcid: 5494038
Rohou, A. & Grigorieff, N. CTFFIND4: fast and accurate defocus estimation from electron micrographs. J. Struct. Biol. 192, 216–221 (2015).
pubmed: 26278980 pmcid: 6760662
Scheres, S. H. W. RELION: implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol. 180, 519–530 (2012).
pubmed: 23000701 pmcid: 3690530
Ilca, S. L. et al. Localized reconstruction of subunits from electron cryomicroscopy images of macromolecular complexes. Nat. Commun. 6, 8843 (2015).
pubmed: 26534841 pmcid: 4667630
Cui, Y., Zhang, Y., Zhou, K., Sun, J. & Zhou, Z. H. Conservative transcription in three steps visualized in a double-stranded RNA virus. Nat. Struct. Mol. Biol. 26, 1023–1034 (2019).
pubmed: 31695188 pmcid: 7526681
DeRosier, D. J. Correction of high-resolution data for curvature of the Ewald sphere. Ultramicroscopy 81, 83–98 (2000).
pubmed: 10998793
Zhang, X. & Zhou, Z. H. Limiting factors in atomic resolution cryo electron microscopy: no simple tricks. J. Struct. Biol. 175, 253–263 (2011).
pubmed: 21627992 pmcid: 3710782
Pettersen, E. F. et al. UCSF chimera—a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).
pubmed: 15264254
Rosenthal, P. B. & Henderson, R. Optimal determination of particle orientation, absolute hand, and contrast loss in single-particle electron cryomicroscopy. J. Mol. Biol. 333, 721–745 (2003).
pubmed: 14568533
Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126–2132 (2004).
pubmed: 15572765
Yu, I. et al. Building atomic models based on near atomic resolution cryoEM maps with existing tools. J. Struct. Biol. 204, 313–318 (2018).
pubmed: 30114513 pmcid: 6754738
Schwede, T., Kopp, J. R., Guex, N. & Peitsch, M. C. SWISS-MODEL: an automated protein homology-modeling server. Nucleic Acids Res. 31, 3381–3385 (2003).
pubmed: 12824332 pmcid: 168927
Kelley, L. A., Mezulis, S., Yates, C. M., Wass, M. N. & Sternberg, M. J. The Phyre2 web portal for protein modeling, prediction and analysis. Nat. Protoc. 10, 845–858 (2015).
pubmed: 25950237 pmcid: 5298202
Afonine, P. V. et al. Towards automated crystallographic structure refinement with phenix.refine. Acta Crystallogr. D Biol. Crystallogr. 68, 352–367 (2012).
pubmed: 22505256 pmcid: 3322595
Berman, H., Henrick, K. & Nakamura, H. Announcing the worldwide protein data bank. Nat. Struct. Biol. 10, 980 (2003).
pubmed: 14634627
Goddard, T. D. et al. UCSF ChimeraX: meeting modern challenges in visualization and analysis. Protein Sci. Publ. Protein Soc. 27, 14–25 (2018).

Auteurs

Wei Liu (W)

California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Microbiology Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Center for Integrative Imaging, Hefei National Laboratory for Physical Sciences at the Microscale, and School of Life Sciences, University of Science and Technology of China, Hefei, China.

Yanxiang Cui (Y)

California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA, USA.
ORCID: 0000-0002-8909-6576

Caiyan Wang (C)

California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Microbiology Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.

Zihang Li (Z)

California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Microbiology Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
ORCID: 0000-0002-4625-9283

Danyang Gong (D)

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Therapeutics Discovery, Amgen Research, Amgen Inc., Thousand Oaks, CA, USA.

Xinghong Dai (X)

California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Microbiology Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.

Guo-Qiang Bi (GQ)

Center for Integrative Imaging, Hefei National Laboratory for Physical Sciences at the Microscale, and School of Life Sciences, University of Science and Technology of China, Hefei, China.
ORCID: 0000-0001-8735-3818

Ren Sun (R)

California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.

Z Hong Zhou (ZH)

California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA, USA. Hong.Zhou@ucla.edu.
Department of Microbiology Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA. Hong.Zhou@ucla.edu.
ORCID: 0000-0002-8373-4717

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Sciences de l'information › Sources d'information › Services d'information › Documentation › Données de séquences moléculaires › Séquence d'acides aminés › Structures of capsid and capsid-associated...
questionsmedicales.fr › Structures virales › Virion › Nucléocapside › Capside › Structures of capsid and capsid-associated...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines virales › Protéines virales structurales › Protéines nucléocapside › Protéines de capside › Structures of capsid and capsid-associated...
questionsmedicales.fr › Techniques d'investigation › Microscopie électronique › Cryomicroscopie électronique › Structures of capsid and capsid-associated...
questionsmedicales.fr › Infection › Maladies virales › Infections à virus oncogènes › Infections à virus Epstein-Barr › Structures of capsid and capsid-associated...
questionsmedicales.fr › Virus › Virus oncogènes › Virus tumoraux à ADN › Gammaherpesvirinae › Lymphocryptovirus › Herpèsvirus humain de type 4 › Structures of capsid and capsid-associated...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Structures of capsid and capsid-associated...
questionsmedicales.fr › Sciences de l'information › Méthodologies informatiques › Traitement d'image par ordinateur › Imagerie tridimensionnelle › Structures of capsid and capsid-associated...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles moléculaires › Structures of capsid and capsid-associated...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Sous-unités de protéines › Structures of capsid and capsid-associated...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Relation structure-activité › Structures of capsid and capsid-associated...
questionsmedicales.fr › Structures virales › Virion › Structures of capsid and capsid-associated...
questionsmedicales.fr › Phénomènes microbiologiques › Phénomènes physiologiques viraux › Réplication virale › Assemblage viral › Structures of capsid and capsid-associated...