Program Director/Principal Investigator (Last, First, IVliddle): ROSSMANN, Michael G.PROJECT SUMr'4ARY (See instructions): When this project started in the early 70's. the objective had been to determine the three-dimensionalatomic resolution structure of a virus - any virus. With the attainment of this goal some eight years later,attention shifted from plant viruses to the greater challenge of animal viruses. The first success came in 1985with the work on human rhinovirus serotype 14. The associated technological developments provided themomentum for structural studies of a large variety of animal, plant and bacterial viruses in the PrincipleInvestigator's laboratory as well as elsewhere. The focus of these projects was the interaction of viruses withcellular factors such as receptors and neutralizing antibodies, the conformational changes that occur duringcell infection, and the assembly of the virus from its constituent parts. Since the mid 90s there have beenmajor advances in the use of cryo-electron microcopy and image reconstruction techniques for structuralstudies of uncrystallizable viral assemblies in combination with crystaliographic investigations of smaller viralcomponents. This has made it possible to obtain 'pseudo-atomic resolution' structures of enormous viruseswith diameters ranging from 1000 to 7,500A and with genomes that provide the potential for most of thefunction of a biological cell. Many of these giant viruses retain at least approximate icosahedral symmetryboth of their capsid and, often, of their internal lipid envelope, providing a handle for the investigation ofparticles that approach the size and complexity of a small bacterium. Currently we are studying three groups of large, icosahedral, dsDNA viruses: (i) the algal Parameciumbursaris chlorella virus-1 (PBCV-1). (ii) the insect Chito irredescent virus (CIV) and (iii) the amoebaMimivirus. We have also initiated X-ray crystaliographic studies of the major capsid proteins of these virusesas well as specific viral proteins such as the unique glycosyltransferases that modify the viral surfaceproteins essential for virus assembly and interaction of the virus with its environment. At the same time the earlier work on small, icosahedral (ssRNA) picorna- and (ssDNA) parvoviruses hascontinued during the current project period as planned. We have studied the interaction of polioviruses,echovoviruses, and Coxsackievirus with their cellular receptors. Similarly, we studied the interaction ofparvoviruses with their cellular receptors and with neutralizing antibodies. The emphasis over the next few years will be on the large icosahedral viruses, their organization andtheir interaction with their hosts, using cryo-electron tomography and electron microscopy of the whole virusand of thin sectioned virus, as well as crystallography of their component parts.
The large dsDNA viruses we are studying are approaching the complexity of a small bacterium. Thus,our current studies of large viruses are gradually merging with the study of small cells as we develop ourtechnology. Although initially we benefitted by the presence of icosahedral symmetry present in theseviruses but not in bacteria, we are now learning how to relinquish strict symmetry to find out more aboutthese viruses and their interactions with cells.
| De Castro, Cristina; Klose, Thomas; Speciale, Immacolata et al. (2018) Structure of the chlorovirus PBCV-1 major capsid glycoprotein determined by combining crystallographic and carbohydrate molecular modeling approaches. Proc Natl Acad Sci U S A 115:E44-E52 |
| Zhu, Dongjie; Wang, Xiangxi; Fang, Qianglin et al. (2018) Pushing the resolution limit by correcting the Ewald sphere effect in single-particle Cryo-EM reconstructions. Nat Commun 9:1552 |
| Baggen, Jim; Thibaut, Hendrik Jan; Staring, Jacqueline et al. (2016) Enterovirus D68 receptor requirements unveiled by haploid genetics. Proc Natl Acad Sci U S A 113:1399-404 |
| Liu, Yue; Hill, Marchel G; Klose, Thomas et al. (2016) Atomic structure of a rhinovirus C, a virus species linked to severe childhood asthma. Proc Natl Acad Sci U S A 113:8997-9002 |
| Klose, Thomas; Reteno, Dorine G; Benamar, Samia et al. (2016) Structure of faustovirus, a large dsDNA virus. Proc Natl Acad Sci U S A 113:6206-11 |
| Liu, Yue; Sheng, Ju; Baggen, Jim et al. (2015) Sialic acid-dependent cell entry of human enterovirus D68. Nat Commun 6:8865 |
| Klose, Thomas; Herbst, Dominik A; Zhu, Hanyu et al. (2015) A Mimivirus Enzyme that Participates in Viral Entry. Structure 23:1058-65 |
| Liu, Yue; Sheng, Ju; Fokine, Andrei et al. (2015) Structure and inhibition of EV-D68, a virus that causes respiratory illness in children. Science 347:71-4 |
| Reteno, Dorine Gaëlle; Benamar, Samia; Khalil, Jacques Bou et al. (2015) Faustovirus, an asfarvirus-related new lineage of giant viruses infecting amoebae. J Virol 89:6585-94 |
| Rossmann, Michael G (2014) Serial crystallography using synchrotron radiation. IUCrJ 1:84-6 |
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