Dr. Watts’ research is focused on two viruses that have great impacts on people’s health, human immunodeficiency virus (HIV-1) and hepatitis B virus (HBV). Globally, 78 million people have been afflicted with HIV since the beginning of the epidemic, 37 million are living with HIV, and over 1 million die annually of related illnesses. HIV-1 expresses a regulatory protein called Rev that is indispensable for viral replication, yet its complete molecular structure remains unknown and there are no therapeutics that target Rev. The Protein Expression Laboratory, in collaboration with the Laboratory of Structural Biology Research, was the first to solve the atomic structure of the amino-terminal domain of Rev. We are currently pursuing the structure of the carboxyl-terminal domain, and also the structures of Rev in complex with viral RNA and with host proteins. In addition, we have generated synthetic antibody fragments targeted against Rev that strongly inhibit HIV replication in peripheral blood mononuclear cells.

Hepatitis B virus (HBV) is a major cause of liver disease in humans, afflicting almost 400 million worldwide, and is the leading cause of hepatic cancer. HBV expresses a protein indispensable to its replication called “core-antigen” (this forms the virus capsid) and a very closely related protein called “e-antigen” whereby the virus blinds the human immune system to its presence. The Protein Expression Laboratory, again in close collaboration with the Laboratory of Structural Biology Research, has closely examined, primarily by electron microscopy, the interaction of core-antigen with not only numerous monoclonal antibodies widely employed in clinical diagnosis but also the entire antibody repertoire in a patient. In addition, our laboratory was the first to determine the molecular structure of the e-antigen, and the remarkable way in which it differs from core-antigen. With this information we have developed not only the first and only completely molecularly defined clinical assay for HBV, but are also developing specific inhibitors of core-antigen and e-antigen function.