IMV Executive Assistant
tel. (612) 624-1926
fax. (612) 625-1108
18-242 Moos Tower
515 Delaware St. SE
Minneapolis, MN 55455
Jose O. Maldonado-Ortiz,
Graduate School Trainee
Phone: (612) 624-5172
HIV-1 mutagenesis and drug resistance; HTLV-1 Gag trafficking and particle assembly
Approximately 30 million individuals have died of AIDS and 33 million are currently infected with human immunodeficiency virus type 1 (HIV-1) worldwide. Highly active antiretroviral therapy (HAART) is currently the best treatment for HIV infection. HAART has dramatically reduced the rate of HIV-1 and AIDS-related morbidity and mortality. However, drug administration may result in drug therapy failure, which is associated with drug resistance mutations. Drug resistance significantly limits the clinical benefit of antiretroviral treatment. I am a D.D.S./Ph.D. dual degree student and my research will thoroughly investigate the biological relevance of the A62V amino acid substitution in HIV-1 reverse transcriptase (RT). The A62V mutation is a substitution observed in HIV-1 clinical isolates that is associated with multi-drug resistance but is known not to be a resistance-conferring mutation. My preliminary studies have discovered that A62V increases HIV-1 mutant frequency. This is the first observation that this residue can influence HIV-1 mutagenesis. In this application, I propose 2 specific aims. In Specific Aim 1, I will investigate a) the role of A62V on virus fitness compared to wt virus using dual competition assay and b) the role of A62V on the efficiency of HIV-1 viral DNA synthesis by real-time PCR. I will also investigate the impact of A62V on HIV-1 mutagenesis in primary T-cells and macrophages using a single cycle replication assay. In Specific Aim 2, I will examine A62V in the context of known multi-dideoxynucleoside resistance (MDR) mutations. In particular, I will thoroughly examine these HIV-1 RT variants for effects on viral fitness, for effects on the efficiency of viral DNA synthesis, and effects on HIV-1 mutagenesis. A better understand HIV-1 population dynamics in the context of antiretroviral therapy is important for predicting disease progression, the durability of antiretroviral drug regimens, and for providing insights into potential vaccine approaches.
Previous molecular analyses of HTLV-1 replication have been severely hampered by the low levels of viral replication in tissue culture. In particular, the low level of viral replication of HTLV-1 in tissue culture has been thought to be due, in part, to the poor infectivity of cell-free HTLV-1 particles. Given the technical and experimental limitations of working with HTLV-1, our group created an experimental model system that is amenable to successfully and efficiently analyzing HTLV-1 particles. My research is using a combination of cryo-EM/ET, scanning transmission electron microscopy (STEM) and FFS to further investigate HTLV-1 particle size and Gag stoichiometry.
'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.
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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.