Research Abstracts Online
January 2009 - March 2010
University of Minnesota Twin Cities
Academic Health Center
Institute for Molecular Virology
PI: Louis M. Mansky
Mechanisms of HIV Variation
The high level of genetic variation of HIV type 1 (HIV-1) is of fundamental importance to the emergence of antiretroviral drug resistance and to the challenges encountered in the development of an effective preventative or prophylactic vaccine. The high virus mutation rate and the high turnover rate of infected cells together help drive virus evolution. Recombination is also thought to play a significant role in shaping population diversity. HIV-1 replication and evolution is thought to be responsible for the gradual breakdown of the immune system and is the mechanism of disease progression to AIDS.
Despite the fundamental importance of HIV-1 variation to therapy and viral pathogenesis, there are many basic principles that remain unexplored or are poorly understood. In this proposal, we propose studies to continue this work. These researchers use MSI resources to explore three lines of investigation to continue this work.
First, they are thoroughly examining the interplay between the HIV-1 mutation rate and viral fitness. Although distinct studies have been performed to analyze each, no comprehensive studies have been performed to date. In particular, they are investigating these aspects of HIV-1 replication by analysis of drug-resistant virus, particularly resistance mutations to nucleoside and non-nucleoside reverse transcriptase inhibitors.
The researchers are also exploring the adaptive evolution HIV-1 mutation rates during the selection of antiretroviral drug resistance. Since in many instances the alteration of mutation rate results in a change in viral fitness, these experiments will help better define the interplay between mutation rate and viral fitness.
Finally, the researchers are investigating the origins of G-to-A transition mutations in HIV-1 proviruses and to determine if frequent, yet sublethal cytosine deamination shapes HIV-1 variation.
Lauren Beach, Graduate Student
Matthew Bess, Graduate Student
Christine Clouser, Research Associate
Jose Cotto, Graduate Student
Michael Dapp, Graduate Student
Casey Dorr, Graduate Student
Keir Fogarty, Research Associate
Willie Greggs, Research Associate
Iwen Grigsby, Research Associate
Colleen Lockman, Graduate Student
Jonathan Rawson, Graduate Student
Holly Sadler, Research Associate
Azah Tabah, Research Associate