Ronald Desrosiers, M.D., Ph.D.
Professor of Pathology
Description of Research
KSHV is the cause of Kaposi’s sarcoma and body cavity based lymphomas in humans. Dr. Desrosiers and his laboratory are the discoverers of a closely related herpesvirus of monkeys called the rhesus monkey rhadinovirus (RRV). They have sequenced the RRV genome, demonstrated the close gene-for-gene homology with human KSHV, developed a genetic system for changing the gene sequences present in the RRV genome, and used this system for experimental infection of rhesus monkeys. A number of different fundamental questions regarding this RRV/KSHV group of viruses are being addressed. What are the cellular receptors used to gain entry into target cells? Are different cellular receptors used to gain entry into different types of target cells? What are the viral glycoproteins used to gain entry into different target cells? The Desrosiers laboratory has recently discovered a remarkable influence of codon usage on regulating expression of glycoproteins as late genes. How do natural transinducers such as orf57 sense the nature of bad codon usage? How do they overcome the restriction against expression of genes with such bad codon usage? What are the cellular proteins imposing this restriction and how do they work? The Desrosiers laboratory has also defined the major cell growth-transforming gene of this group of viruses, a gene called STP in the gamma-2 herpesvirus of New World primates (herpesvirus saimiri), R1 in RRV and K1 in KSHV.
Dr. Desrosiers’ laboratory is interested in how individual viral genes contribute to the successful survival strategies employed by persisting viruses. Viruses under study include KSHV, the AIDS virus HIV, and the monkey homologs of these viruses (RRV and SIV). His approach includes laboratory-based research and use of monkey models of these human viral infections. Lessons learned at a basic fundamental level are applied to the quest for an effective vaccine against HIV/AIDS. The Desrosiers' laboratory, as well as a few other laboratories around the world, are exploring the use of persistent recombinant herpesviruses for the elicitation of persistent anti-SIV immune responses that can be protective against SIV in monkeys.
- Discovery of the simian immunodeficiency virus and development of its use for AIDS pathogenesis and vaccine research
- Discovery of the gamma-2 herpesvirus called RRV that is a close monkey homolog of the Kaposi sarcoma herpesvirus (human herpesvirus 8).
- Identification and characterization of the most important transforming gene of the gamma-2 herpesviruses
- Discovery of the first infectious pathogenic molecular clone of any lentivirus
- Characterization of the relative importance and functional contribution of the auxiliary genes of SIV.
- Identification of natural cases of humans infected with attenuated strains of HIV-1, including the first report of a human infected with nef-deleted HIV-1.
- Demonstration on the protective effects of live attenuated strains of SIV as vaccines
Selected Cancer-Related Publications
Collaborating in the Multidisciplinary Research Program(s):