Structural Analysis of Virulence Determinants and Genomic DNA Packaging Constraints in a ssDNA Virus

University Of Florida, Gainesville FL

Investigators

Abstract

Capsid proteins play many functional roles during the life cycle of viruses, including host cell recognition, specific encapsidation of genomic nucleic acid, and the formation of the essential interactions required for progeny virus capsid assembly and release. For the ssDNA Parvoviridae, the exact role of their capsid proteins in these processes requires further elucidation. Genetics studies have shown that interaction of the major parvoviral capsid protein, VP2, with host cell factors play a crucial role in tissue tropism and entry into the host cell. The methodologies of X-ray crystallography, biochemistry and virology will be utilized to study two closely related strains of minute virus of mice, MVMi (immunosuppressive strain) and MVMp (prototype strain) and their interactions with sialic acid, a component of their infectious receptor, to gain insights into mechanisms of specificity of capsid interactions in virulence determination. In addition, the X-ray structure of MVMi, in which approximately 30% of the ssDNA genome is ordered provides a unique model for defining molecular interactions between a viral capsid and its genome that ensure selective recognition and packaging. The aim is to identify a possible genomic signature that drives parvoviral DNA recognition and encapsidation. Research developments and achievements will be integrated with educational training of senior undergraduate and graduate students in the use of a multidisciplinary approach to study macromolecular interactions.