RNA aptamers and HIV reverse transcriptase : molecular basis of their interactions and the evaluation of aptamer resistance

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[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI SYSTEM AT REQUEST OF AUTHOR.] Human Immunodeficiency virus (HIV) is a pandemic Lentivirus that causes acquired immune deficiency syndrome (AIDS) in infected individuals. One of the critical steps in HIV replication is the reverse transcription of viral RNA to generate viral DNA, which will be integrated into the host genome to generate materials for the production of new viruses. The enzyme responsible for this reverse transcription process is HIV reverse transcriptase (RT). Because of its importance in HIV life cycle, RT has been a common target for HIV inhibitors. In recent years, RNA aptamers have emerged as potential inhibitors against HIV RT. Although previous studies had shown that the inhibitory effect of RNA aptamers against HIV RT comes from their ability to compete with primer/template for binding to RT, the molecular details of RT-RNA aptamer interaction are still limited. The work described herein highlights advancements in identifying the functional features of a broad-spectrum RNA aptamer and elucidating the molecular details in the interaction of this aptamer and the target RT. Furthermore, this work explores the potential use of anti HIV aptamers in studying RT maturation by proteolytic processing.

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