Dr. Imperiale's laboratory studies the molecular biology of the small DNA tumor viruses. They are particularly interested in how these viruses assemble, how they deregulate normal cell growth control, and how they interact with the host immune system.
One major area of study is the interaction of the human polyomavirus, BKV, with the host cell. BKV is a DNA virus that establishes a subclinical, persistent infection of the urinary tract. In healthy individuals, the virus does not cause disease, but in renal and bone marrow transplant patients, the virus can reactivate and cause life threatening illness. Dr. Imperiale and his lab are interested in the interplay between viral and host factors that allow the virus to persist in the presence of a healthy immune system, as well as those that drive lytic replicatio when the immune system is suppressed. They have demonstrated that interferon-g can inhibit viral transcription in renal proximal tubular epithelial cells, the natural host cell for the virus. Their current efforts are aimed at determining the mechanism of inhibition, which may involve nuclear structures called PML nuclear bodies. These have been shown to be involved in the interferon response to other DNA viruses.
Another project involves assembly of adenovirus, a virus that is a major cause of upper respiratory and ocular infections in children, and that also can cause serious illness in the transplant setting. Dr. Imperiale and his lab have identified two viral proteins, the L1 52/55 kDa protein and the IVa2 protein, that are required for packaging of the viral genome into capsids. Moreover, it appears that the IVa2 protein is required for capsid assembly. They are currently attempting to elucidate the mechanism by which these two proteins function to allow the virus to encapsidate its DNA. These studies will enhance our knowledge of how the virus carries out this important step in its life cycle.