Studies On The Antiretroviral Mechanism Of Action Of Clofarabine

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Studies On The Antiretroviral Mechanism Of Action Of Clofarabine

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Beach, Lauren

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2014-07

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Abstract

Since the beginning of the AIDS epidemic over thirty years ago, human immunodeficiency virus type 1 (HIV-1) has infected seventy-five million people and has claimed the lives of over thirty-six million people worldwide, making HIV/AIDS one of the most devastating global infectious disease epidemics in history. To date, no preventative vaccine or curative treatment exists for HIV-1 infection. The availability of drugs to treat HIV-1 infection has led to drug resistance, which limits the utility of antiviral therapy. This has provided the basis for the continual need for identifying new targets for antiviral drugs. This dissertation investigated the antiretroviral activity and mechanism of action for clofarabine, a purine nucleoside antimetabolite. Clofarabine was demonstrated to exert antiretroviral activity against both HIV-1 and human immunodeficiency virus type 2 (HIV-2). Studies directed at elucidating the antiretroviral mechanism of action support a model in which clofarabine acts as an inhibitor of ribonucleotide reductase, leading to imbalances in cellular dNTP pools, which reduces viral infectivity through an increase in the HIV-1 mutation rate.

Keywords

AIDS

Clofarabine

HIV-1

HIV-2

Retrovirus

Ribonucleotide Reductase Inhibitors

Description

University of Minnesota Ph.D. dissertation. July 2014. Major: Molecular, Cellular, Developmental Biology and Genetics. Advisor: Louis Mansky. 1 computer file (PDF); xi, 143 pages.

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Beach, Lauren. (2014). Studies On The Antiretroviral Mechanism Of Action Of Clofarabine. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/174838.

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