Three-dimensional structure and functional investigations will examine early (attachment, entry, uncoating) and late (assembly, exit from the host cell, transmission to other cells) stages of viral infection. The principal tools will be X-ray crystallography, electron microscopy and molecular biology. Viral infectivity will be probed with antibodies, site-directed and selected mutations, antiviral agents that block specific stages in the infectious process, soluble and membrane-bound receptors, pH and temperature variation and changes of the environment that alter capsid stability. The viruses currently under investigation at Parti include picornaviruses, alphaviruses, parvoviruses and retroviruses infecting vertebrates; alphaviruses, nodaviruses and Nudaurelia viruses infecting insects; comoviruses, cowpea chlorotic mottle virus and barley yellow dwarf virus infecting plants; and a phage infecting E. coli. Only some of these studies are to be funded by this application. Because plant viruses can, in general, be obtained in much larger quantities than animal viruses, the cowpea mosaic virus, cowpea chlorotic mottle virus and barley yellow dwarf virus systems will come in useful to develop techniques and background knowledge. Indeed, the availability of plant viruses was the reason why the first virus structures were of plant viruses. The proximity of the groups on the same floor of one building permits exchange of crystallographic and computing technology as well as virological and molecular biological techniques. Collaborations on specific virus systems are in progress on picornaviruses, barley yellow dwarf virus and cucomoviruses, alphaviruses, and como-, tetra- and nodaviruses. The existing core facility encompasses a crystallographic and computing laboratory, an electron microscopy laboratory and a containment laboratory for cell culture, virus propagation and purification.
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