Roberto Mateo, Ph.D.
Postdoctoral Fellow

Ph. D. Molecular Biology, Universidad Autónoma de Madrid, 2004
B.S. Biochemistry, Universidad del País Vasco, 1999
D321 Fairchild
299 Campus Drive
Stanford CA 94305-5124
Research Summary

The high error rate of RNA-dependent RNA polymerases responsible for RNA viral genome replication presents an enormous challenge to successful drug therapy due to the high probability of mutations that can confer resistance to any antiviral pharmaceutical.

Our laboratory has devoted considerable time to understanding the transmission genetics of positive-strand RNA viruses. Recently, the laboratory of Karla Kirkegaard has consolidated this research to show that for polioviruses, choices of drug target can be made so that drug-sensitive genomes dominantly inhibit the outgrowth of drug-resistant genomes. In particular, all lethat mutations made in the capsid proteins of poliovirus were found to be dominant, inhibiting the growth of wild-type virus in the same cell. A viral capsid is an excellent example of a highly oligomeric structure required for sucessful virus production, which means that capsid proteins encoded by different genomes within the same cell can mix to form chimeric capsids that could destroy the function of all virions that assemble in the same cell. As the first example of a dominant, drug-sensitive genome, our laboratory has shown that co-infections between pleconaril-resistant and pleconaril-sensitive polioviruses gave rise to viral progeny with poor pleconaril resistance. This provides a strong rationale for the development of inhibitors to the assemby and function of capsid proteins of RNA viruses. My goal is to extend these observations described for poliovirus to other RNA viruses; in particular my project is focussed on screening for small organic compounds that will derange assembly of dengue C capsid protein and test our working hypothesis that capsid proteins sensitive to the drug will slow the growth of other, drug-resistant genomes. This will serve as a proof of principle that the basic genetic strategies of RNA virus replication can be exploited to fight them in a highly effective way.

Copyright 2006 - 2007. The Laboratory of Karla Kirkegaard, Ph.D. All rights reserved.