Minnesota 554554 ?

Is 554554 the post code of "Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota"?

Context:

Exploiting Drug Repositioning for Discovery of a Novel HIV Combination Therapy

Christine L. Clouser,1,2 Steven E. Patterson,3 and Louis M. Mansky1,2,3,4*
Institute for Molecular Virology,1 Department of Diagnostic and Biological Sciences, School of Dentistry,2 Center for Drug Design,3 Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota 554554
Received 8 May 2010/ Accepted 29 June 2010

The development of HIV drugs is an expensive and a lengthy process. In this study, we used drug repositioning, a process whereby a drug approved to treat one condition is used to treat a different condition, to identify clinically approved drugs that have anti-HIV activity. The data presented here show that a combination of two clinically approved drugs, decitabine and gemcitabine, reduced HIV infectivity by 73% at concentrations that had minimal antiviral activity when used individually. Decreased infectivity coincided with a significant increase in mutation frequency and a shift in the HIV mutation spectrum. These results indicate that an increased mutational load is the primary antiviral mechanism for inhibiting the generation of infectious progeny virus from provirus. Similar results were seen when decitabine was used in combination with another ribonucleotide reductase inhibitor. Our results suggest that HIV infectivity can be decreased by combining a nucleoside analog that forms noncanonical base pairs with certain ribonucleotide reductase inhibitors. Such drug combinations are relevant since members of these drug classes are used clinically. Our observations support a model in which increased mutation frequency decreases infectivity through lethal mutagenesis.