Recent studies appear to associate natural SV40 strains with human brain tumors in early childhood. The goal of Dr. Harumi Kasamatsu's research is to understand the pathways that contribute to the formation of the DNA tumor virus, SV40, and to understand how tumor antigens play a role in viral morphogenesis.
Currently, Kasamatsu's work concerns defining the individual protein domains of SV40 structural proteins that determine the individual steps in the morphogenesis and relating these domains to their biological activities. She and her colleagues are using various molecular, biological, genetic, biochemical and immunological approaches to ask questions, specifically:
- What is the structural determinant for the nuclear targeting of an infectious virion particle, and what is the mechanism of the targeting?
- What components of SV40 are important for viral DNA targeting?
- How are individual proteins intracellularly targeted to the nucleus following their synthesis?
- What are the determinants of individual proteins that specify protein-protein interactions?
- Where and how do the interactions of each protein leading to virion assembly occur?
- What are the determinants that initiate genome packaging and how does the packaging occur?
A basic understanding of the functional determinants is indispensable toward understanding which ones mediate infection and which ones prevent the spread of the DNA tumor viruses. Success in identifying the component and specific protein domains of viral proteins responsible for effective nuclear targeting of SV40 DNA may lead to the development of a general, effective means to exogenously introduce DNA or tumor killing reagent into mammalian cells.
Selected Cancer-Related Publications:
Nakanishi A, Li PP, Qu Q, Jafri QH, Kasamatsu H. Molecular dissection of nuclear entry-competent SV40 during infection. Virus Res. 2007; 124(1-2): 226-30.
Li PP, Nguyen AP, Qu Q, Jafri QH, Aungsumart S, Cheng RH, Kasamatsu H. Importance of calcium-binding site 2 in simian virus 40 infection. J Virol. 2007; 81(11): 6099-105.
Nakanishi A, Itoh N, Li PP, Handa H, Liddington RC, Kasamatsu H. Minor capsid proteins of simian virus 40 are dispensable for nucleocapsid assembly and cell entry but are required for nuclear entry of the viral genome. J Virol. 2007; 81(8): 3778-85.
Kasamatsu H, Woo J, Nakamura A, Muller P, Tevethia MJ, Liddington RC. A structural rationale for SV40 Vp1 temperature-sensitive mutants and their complementation. Protein Sci. 2006; 15(9): 2207-13.
Nakanishi A, Nakamura A, Liddington R, Kasamatsu H. Identification of amino acid residues within simian virus 40 capsid proteins Vp1, Vp2, and Vp3 that are required for their interaction and for viral infection. J Virol. 2006; 80(18): 8891-8.