Our research studies three stages of the retroviral life-cycle: entry, replication and integration. Retroviruses are RNA viruses capable of inducing various diseases including cancers and immunodeficiencies. The focus of our research is to study three stages in the infectious retroviral life cycle. These include the entry, replication and integration of the virus.
Entry: Retroviral entry is defined by the interaction of the host receptor protein with the viral envelope proteins. Retroviruses are frequently used as a means of gene delivery for gene therapy. We have developed a new approach to retarget the retroviral entry to novel receptors using a mammalian Env random display library. This system is now being applied to biologically relevant systems including cancer cells. The ability to specifically target viral entry into selective cells has widespread applications.
Additional studies aim at understanding on the molecular level the mechanism by which Murine Leukemia Viruses choose and enter their host cells. Viral gene products are known to be required for the entry of the virus into cells. In our laboratory these proteins, the Envelope gene products. are studied genetically and biochemically.
Replication and Integration: The retroviral pol gene encodes the reverse transcriptase (RT) and integrase (IN) proteins. Our research involves the expression, purification and characterization of the reverse transcriptase and integrase proteins. The reverse transcriptase is a multifunctional protein, which replicates the viral RNA into double-stranded DNA form. This DNA product is subsequently integrated into the host DNA, a reaction requiring the viral integrase. A main focus of the studies on viral integration involve the X-ray crystallographic analysis of the MuLV integrase protein and subdomains.