Dr. Prashant Desai
Associate Professor of Oncology
Ph.D., University of Cambridge
Postdoctoral Fellow, Department of Human Genetics, University of Michigan, Ann Arbor
Postdoctoral Fellow, Department of Molecular Genetics and Biochemistry, University of Pittsburgh
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.
Okoye, M.E.; Sexton, G.L.; Huang, E.; McCaffery, J.M.; Desai, P. Functional analysis of the triplex proteins (VP19C and VP23) of herpes simplex virus type 1. J Virol. 2006 Jan;80(2):929-940.
Huang, E.; Perkins, E.M.; Desai, P. 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. 2007 Sep;81(17):9396-9407.
Sole, M.; Perkins, E.M.; Frisancho, A.; Huang, E.; Desai, P. 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. 2007 Aug;81(15):8367-8370.
Desai, P.; Sexton, G.L.; Huang, E.; Person, S. Localization of herpes simplex virus type 1 UL37 in the Golgi complex requires UL36 but not capsid structures. J Virol. 2008 Nov;82(22):11354-11361.
Perkins, E.M.; Anacker, D.; Davis, A.; Sankar, V.; Ambinder, R.F.; Desai, P. Small capsid protein pORF65 is essential for assembly of Kaposi's sarcoma-associated herpesvirus capsids. J Virol. 2008 Jul;82(14):7201-7211.
Henson, B.W.; Perkins, E.M.; Cothran, J.E.; Desai, P. Self-assembly of Epstein-Barr virus capsids. J Virol. 2009 Apr;83(8):3877-3890.
Oh, M.J.; Akhtar, J.; Desai, P.; Shukla, D. A role for heparan sulfate in viral surfing. Biochem Biophys Res Commun. 2009 Nov 10: in press.
Zhu, J.; Liao, G.; Shan, L.; Zhang, J.; Chen, M.R.; Hayward, G.S.; Hayward, S.D.; Desai, P.; Zhu, H. Protein array identification of substrates of the Epstein-Barr virus protein kinase BGLF4. J Virol. 2009 May;83(10):5219-5231.
Alcendor, D.J.; Knobel, S.M.; Desai, P.; Zhu, W.Q.; Vigil, H.E.; Hayward, G.S. KSHV downregulation of galectin-3 in Kaposi's sarcoma. Glycobiology. 2010 May;20(5):521-532.
Oh, M.J.; Akhtar, J.; Desai, P.; Shukla, D. A role for heparan sulfate in viral surfing. Biochem Biophys Res Commun. 2010 Jan 1;391(1):176-181.
Henson, B. W., Johnson, N., Bera, A., Okoye, M. E., Desai, K. V., and P. J. Desai. 2011. Expression of the HSV-1 capsid protein VP19C in Escerichia coli: A single amino acid change overcomes an expression block of the full-length polypeptide. Protein Expr. Purif. 77:80-85.
KSHV regulation of fibulin-2 in Kaposi's sarcoma: implications for tumorigenesis. Alcendor DJ, Knobel S, Desai P, Zhu WQ, Hayward GS. Am J Pathol. 2011 Sep;179(3):1443-54. Epub 2011 Jul 7.