STRUCTURAL STUDIES OF THE SSDNA PARVOVIRUSES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The aim of our projects on the ssDNA viruses is to identify structural determinants of receptor attachment, tissue tropism, in vivo pathogenicity, and transduction efficiencies between highly homologous Parvoviridae strains and serotypes. Our structural studies so far indicate that slight capsid surface alterations, resulting from amino acid differences, are associated with pronounced differences in biological properties during the viral life cycle of parvoviruses. The long-term goal of our studies are to utilize the structural information obtained for the design of viral vaccines, foreign antigenic delivery systems, viral gene therapy vectors for the treatment of animal and human diseases. This rapid mode application is to obtain experimental beam time for X-ray diffraction data collection on the adeno-associated virus serotypes 4, 5 and 8 (AAV4, AAV5 and AAV8)¿¿¿¿¿"being exploited for gene therapy applications and the prototype strain of minute virus of mice (MVMp). We aim to collect native data on crystals of AAV5 and AAV8 for which there is no structural information and to collect data for AAV4 and MVMp on crystals soaked or co-crystallized with trisaccharide components (containing sialic acid) of their cell surface receptors. The structures of wt AAV4 and MVMp have already been determined, with X-ray diffraction data collected at either the F1 station at CHESS.