Research Interests
Recent studies have associated natural strains of simian virus 40 (SV40) with human brain tumors of early childhood. The goal of our research is to understand the pathways that contribute to the formation of a DNA tumor virus, namely, SV40, and to understand how tumor antigens play a role in viral morphogenesis. Currently, our work seeks to define individual functional domains of SV40 structural proteins that determine the individual steps in the morphogenesis, to relate these domains to their biological activities. We are using molecular biological, genetic, biochemical, and immunological approaches to ask various questions, specifically: (1) What is the structural determinant for the nuclear targeting of an infectious virion particle, and what is the mechanism of the targeting? (2) What components of SV40 are important for viral DNA targeting? (3) How does the newly synthesized major coat protein fold and form a capsomere, a building block of the virion, in the cytoplasm? (4) How are individual proteins intracellularly targeted to the nucleus following their synthesis? (5) What are the determinants of individual proteins that specify protein-protein interactions? (6) Where and how do the interactions of each protein occur during virion assembly? (7) What are the determinants that initiate genome packaging, and how does the packaging occur? A basic understanding of the functional determinants is indispensable for identifying the protein determinants that mediate infection and for devising measures that can prevent the spread of DNA tumor viruses. Successful identification of specific viral protein domains responsible for the effective nuclear targeting of SV40 DNA may lead to the development of a general, effective means to exogenously introduce therapeutic DNA or tumor killing reagents into mammalian cells.
Selected Publications
Nakanishi, A., Itoh, N., Li, P.P., Handa, H., Liddington, R.C. and Kasamatsu, H.. 2007. Minor capside proteins of SV40 are dispensable for nucleocapsid assembly and cell entyr, but are required for nuclear entry of the viral genome J. Virol 81: 3778-3785 .
Li, P.P., Nguyen, A.P., Qu, Q., Jafri, Q.H. Aungsumart, S., Cheng, R.H. and Kasamatsu, H.. 2007. Importance of calcium-binding site 2 in simian virus 40 infection J. Virol 81: 6099-6105 .
Nakanishi, A., Nakamura, A., Liddington, R. and Kasamatsu, H.. 2006. 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 80: 8891-8898 .
Nakanishi, A., Li, P.P., Qu, Q., Jafri, Q.H. and Kasamatsu, H.. 2006. Molecular dissection of nuclear entry-competent SV40 during infection Virus Res 124: 226-230 .
Li, P.,P., Nakanishi, A., Fontanes, V. and Kasamatsu, H.. 2005. Pairs of Vp1 Cysteine Residues Essential for Simian Virus 40 Infection J. Virol 79: 3859-3864 .
Nakanishi, A., Shum, D., Morioka, H., Otsuka, E., and Kasamatsu, H.. 2003. Interaction of the Vp3 nuclear localization signal with the importin a2/ß heterodimer directs nuclear entry of infecting simian virus 40 J. of Virol 76: 9368-9377 .
Li, P.P., Nakanishi, A., Tran, M.A., Ishizu, K.-I., Kawano, M., Harda, H., Liddington, R.C., and Kasamatsu, H.. 2003. Importance of Vp1 calcium-binding residues in assembly, cell entry, and nuclear entry of simian virus 40 J. Virol 77: 7527-7538 .
Li, P.P., Nakanishi, A., Clark, S., and Kasamatsu, H.. 2002. Formation of transitory intrachain and interchain disulfide bonds accompanies the folding and oligomerization of simian virus 40 Vp1 in the cytoplasm Proc. Natl. Acad. Sci. USA 99: 1353-1358 .
Li, P.P., Nakanishi, A., Shum, D., Sun, P.C.-K., Salazar, A.M., Fernandez, C.F., Chan, S.-W. and Kasamatsu, H.. 2001. Simian virus 40 Vp1 DNA binding domain is functionally separable from the overlapping nuclear localization signal and is required for effective virion formation and full viability J. Virol 75: 7321-7329 .
Li, P.P., Nakanishi, A., Tran, M.A., Salazar, A.M., Liddington, R.C. and Kasamatsu H.. 2000. Role of simian virus 40 Vp1 cysteines in virion infectivity J. Virol 74: 11388-11393 .