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The major focus of the laboratory is to understand how herpes simplex virus utilizes cellular machinery to optimize its own assembly. The work is divided into two areas. The first area of interest focuses on the process of DNA cleavage and packaging within infected cell nuclei; the process is the target of a novel class of antiviral drugs currently under development. We have discovered that herpesvirus capsids utilize actin to allow capsids to move in a directed fashion in infected cell nuclei. This is done by tracking capsids tagged with green fluorescent protein in living cells by time lapse cofocal microscoopy. These studies should shed light on the roles of actin-dependent motors in the nucleus; such motors have been implicated in intranuclear movement of chromosome remodeling complexes and telomeres, among other structures. A second area concerns envelopment of nucleocapsids at the inner nuclear membrane. We have identified proteins, essential to envelopment of nucleocapsids, that alter the structure of the nucleus, presumably to allow efficient production of virions by facilitating budding at the inner nuclear membrane. The goal of this research is to determine how the HSV proteins alter the nuclear cytoskeleton and mediate nucleocapsid trafficking through the nuclear lamina which forms a fibrous barrier and acts to fortify the structure of the nucleus. This should shed light not only on envelopment of nucleocapsids, but also the functions of the nuclear lamins.
Dr. Baines is a member of the following Graduate Fields:
Elizabeth Wills, a research technical expert in electron microscopy and monoclonal antibody production.
Forest, T, Barnard, S. and J.D. Baines. (2005) Active intranuclear movement of herpes simplex virus capsids. Nature Cell Biology 7:429-431. Park, R. and J.D. Baines (2006) Herpes simplex virus type 1 infection induces activation and recruitment of protein kinase C to the nuclear membrane and increased phosphorylation of lamin B. J. Virol. 80:494-504. (Featured article) Yang, K and J.D. Baines (2006) The putative terminase subunit of herpes simplex virus 1 encoded by UL28 is necessary and sufficient to mediate interaction between pUL15 and pUL33. J. Virol. 80:5733-5739. Baines, J.D., Hsieh, C., Wills, E., Mannella, C., Marko, M. (2007). Electron tomography of nascent herpes simplex virus 1 virions. J.Virol. 81:2726-2735 (Editor-featured article - cover photograph). Yang, K., Homa, F., and, J.D. Baines. (2007). Putative terminase subunits of herpes simplex virus 1 form a complex in the cytoplasm and interact with portal protein in nuclei of infected cells. Epub. March 23. J. Virol. 81:6419-6433. Mou, F., Forest, T. and J.D. Baines. (2007). US3 of Herpes Simplex type 1 Encodes a Promiscuous Protein Kinase that Phosphorylates and Redistributes Lamin A/C in infected cells. Epub. April 16. J. Virol. 81:6459-6470. |