IMV Executive Assistant
tel. (612) 624-1926
fax. (612) 625-1108
18-242 Moos Tower
515 Delaware St. SE
Minneapolis, MN 55455
Graduate School Trainee
Phone: (612) 624-5172
HIV-1 & HIV-2 genetic diversity & evolution; HIV lethal mutagenesis
Two distinct types of HIV are found in humans—HIV-1 and HIV-2. HIV-1 is the major cause of the global pandemic. In contrast, HIV-2 has stayed concentrated in West Africa, where it is estimated to infect 1-2 million people. HIV-2 differs from HIV-1 in several other important ways as well: HIV-2 encodes an additional gene that is missing in HIV-1, HIV-2 is poorly transmitted, and HIV-2 is much less pathogenic than HIV-1, leading to AIDS in only a minority of untreated individuals. Therefore, HIV-2 is often thought of as an attenuated model of HIV-1 infection. Unfortunately, the biological basis for the attenuated pathogenicity of HIV-2 is still poorly understood. These differences in pathogenicity could be explained by varying mutation rates, and, indeed, several observations suggest that HIV-1 and HIV-2 might differ in terms of viral mutation. First, the HIV-2 RT (the major generator of mutations in HIV) is quite distinct (~40%) from the HIV-1 RT in terms of its protein sequence. Second, HIV-2 naturally contains polymorphisms in RT, such as V75I, that have been proven to alter RT fidelity in HIV-1. Third, HIV-2 has been proposed to evolve more slowly than HIV-1, which could be due to a lower mutation rate. For these reasons, we decided to investigate whether HIV-1 and HIV-2 differ in viral mutation.
I am working with Tara Peterson (undergraduate researcher in the Mansky lab) to unravel the basic biological differences that are responsible for the reduced pathogenicity of HIV-2 observed clinically. Though HIV-2 is less prevalent than HIV-1 worldwide, uncovering the basis of its reduced pathogenicity is valuable because it would likely impact HIV-1 treatment and prevention strategies. If, as we hypothesize, we find that HIV-2 has a lower mutation rate than HIV-1, it would support a model in which HIV-2 is less pathogenic because it can’t mutate quickly enough to efficiently escape the host immune response. This finding would support the development of therapeutic strategies against HIV-1 that act by blocking viral mutation.
Rawson, JM, Heineman, RH, Beach, LB, Martin, JL, Schnettler, EK, Dapp, MJ, Patterson, SE, Mansky, LM. 2013. 5,6-Dihydro-5-aza-2'-deoxycytidine potentiates the anti-HIV-1 activity of ribonucleotide reductase inhibitors. Bioorganic and Medicinal Chemistry. 21:7222-7228.
'Wisc-e-sota', a Joint UMN-UW Virology Training Grant Symposium was first held on Friday, Sepbember 20th, 2013 at the Uniiversity of Wisconsin-La Crosse, Cartwright Center. This was the inaugural collaborative symposium of the NIH T32-supported virology training programs at the University of Wisconsin-Madison and the University of Minnesota-Twin Cities. Talks and poster sessions were presented by students, postdocs and faculty. The second UMN-UW Virology Training Grant Symposium will be held in the Fall 2014. Details to follow.
The 2014 IMV Symposium will be held on May 12, 2014 and Mark Denison (Vanderbilt) and Bert Semler (UC-Irvine) will be the Keynote Speakers. Click on the link below to register and submit abstracts.
Read about bacteriophage phi 29 and why it matters.
Explore nearly a century's worth of discovery in the field of virology at the University of Minnesota.
"This Week in Virology" from professor Vincent Racaniello.