Prashant Desai, Ph.D.
Titles
Assistant Professor of Oncology
Schools/Degrees
Ph.D., University of Cambridge
Training
Postdoctoral Fellow, Department of Human Genetics, University of Michigan, Ann Arbor
Postdoctoral Fellow, Department of Molecular Genetics and Biochemistry, University of Pittsburgh
Research Summary
The herpesvirus capsid comprises seven proteins that together form a large complex assembly. The intimate association of these proteins to create a protective shell around the virus genome requires multiple protein-protein interactions. These interactions drive the self-assembly of this structure. Assemblies of large protein complexes are evident in a number of cellular systems, including transcription, protein translation, molecular motors and protein degradation. Thus, defining how these multiprotein assemblies associate and interact and characterizing their structural features is a fundamental problem in biology.
The protein coat that protects the virus genomes has been studied as a paradigm for how proteins interact and self-assemble into higher-order structures. Our research addresses the interactions between the herpes simplex virus type 1 (HSV-1) capsid proteins and the residues that mediate these interactions. The structural features of these multiprotein complexes will be analyzed from isolated complexes and in the context of the capsid shell. The validation of an antiviral target depends on the information gained from identification of interactive domains and their structural characteristics.
Herpesviruses have evolved mechanisms that subvert and hijack normal cellular activities to propagate their progeny. Our goal is to understand the mechanism by which the virus acquires its infectious coat and the role of the virus-encoded functions in this pathway, primarily by analyzing the functions of two tegument proteins, the UL36 and UL37 gene products. The goals of this research program are to understand how these two proteins function in the morphogenesis of the infectious particle and identify the functional domains required for these activities and the interactions that occur during this process. This could potentially lead to the discovery of novel pathways that can be targeted by antiviral intervention.
Journal Citations
Desai, P., Sexton, G.L., Huang, E., and Person, S. (2008). Localization of herpes simplex virus type 1 UL37 in the Golgi complex requires UL36 but not capsid structures. J Virol 82, 11354-11361.
Huang, E., E. M. Perkins, and P. Desai. 2007. Structural features of the scaffold interaction domain at the N terminus of the major capsid protein (VP5) of herpes simplex virus type 1. J Virol 81:9396-407.
Okoye, M. E., Sexton, G. L., Huang, E., McCaffery, J. M. & Desai, P. (2006). Functional analysis of the triplex proteins (VP19C and VP23) of herpes simplex virus type 1. J Virol 80, 929-40.
Perkins, E.M., Anacker, D., Davis, A., Sankar, V., Ambinder, R.F., and Desai, P. (2008). Small capsid protein pORF65 is essential for assembly of Kaposi's sarcoma-associated herpesvirus capsids. J Virol 82, 7201-7211.
Sole, M., E. M. Perkins, A. Frisancho, E. Huang, and P. Desai. 2007. The N terminus of the herpes simplex virus type 1 triplex protein, VP19C, cannot be detected on the surface of the capsid shell by using an antibody (hemagglutinin) epitope tag. J Virol 81:8367-70.
Desai, P., Akpa, J. C., & Person, S. 2003. Residues of VP26 of herpes simplex virus type 1 that are required for its interaction with capsids. J. Virol. 77:391-404.
Desai, P., Sexton, G. L., McCaffery, J. M., & Person, S. 2001. A null mutation in the gene encoding the herpes simplex virus type 1 UL37 polypeptide abrogates virus maturation. J. Virol. 75:10259-10271.
Grunewald, K., Desai, P., Winkler, D. C., Heymann, J. B., Belnap, D. M., Baumeister, W., et al. 2003. Three-dimensional structure of herpes simplex virus from cryo-electron tomography. Science. 302:1396-1398.
Walters, J. N., Sexton, G. L., McCaffery, J. M., & Desai, P. 2003. Mutation of single hydrophobic residues, I27, L35, F39, L58, L65, L67 or L71 in the N-terminus of VP5 abolish interaction with the scaffold protein and abrogate closure of herpes simplex virus type 1 capsid shells. J. Virol. 77:4043-4059.
Warner, S. C., Chytrova, G., Desai, P., & Person, S. 2001. Mutations in the N-terminus of VP5 alter its interaction with the scaffold proteins of herpes simplex virus type 1. Virology. 284:308-316.
