University of Virginia Health System

Email Address: dhk3k@virginia.edu

Kaposi's sarcoma (KS), the most common AIDS-associated malignancy, is caused by the human herpesvirus, KSHV. Nevertheless, the details of KSHV infection and pathogenesis remain unclear. A rare type of B cell lymphoma (PEL) also arising from KSHV infection, has allowed the development of cell lines that produce KSHV in culture. These lines have allowed the study of viral structure, assembly, gene expression and pathogenesis. Our investigations involve four major areas:

1. Isolation and characterization of viral genes and their protein products involved in KSHV pathogenesis. In particular we are interested in the mechanisms underlying the virus’s ability to evade host cell defenses as well as to activate and potentially exploit host signal transduction pathways.

2. Determination of the protein composition, spatial arrangement and assembly of viral and subviral particles. Our approaches include the coupling of classical molecular biology and virology with biochemistry, electron microscopy (EM), immuno-EM and cryo-EM.

3. Development of a transgenic mouse model of KSHV infection that will allow us to monitor the cellular immune response to viral proteins (antigens), taking advantage of a transgenic mice expressing human HLA molecules.

4. Identification of the cell types initially infected during primary transmission of KSHV in humans, including understanding better the intracellular milieu favoring latent versus lytic stages of the viral life cycle.