HIV-1 and Human PEG10 Frameshift Elements Are Functionally Distinct and Distinguished by Novel Small Molecule Modulators
Tony S Cardno, Yosuke Shimaki, Brad E Sleebs, Kurt Lackovic, John P Parisot, Rebecca M Moss, Caillan Crowe-McAuliffe, Suneeth F Mathew, Christina D Edgar, Torsten Kleffmann, Warren P Tate
PLoS One | PUBLIC LIBRARY SCIENCE | Published : 2015
Frameshifting during translation of viral or in rare cases cellular mRNA results in the synthesis of proteins from two overlapping reading frames within the same mRNA. In HIV-1 the protease, reverse transcriptase, and integrase enzymes are in a second reading frame relative to the structural group-specific antigen (gag), and their synthesis is dependent upon frameshifting. This ensures that a strictly regulated ratio of structural proteins and enzymes, which is critical for HIV-1 replication and viral infectivity, is maintained during protein synthesis. The frameshift element in HIV-1 RNA is an attractive target for the development of a new class of anti HIV-1 drugs. However, a number of exa..View full abstract
Awarded by Health Research Council of New Zealand's International Investment Opportunities Fund
Awarded by National Health and Medical Research Council of Australia
This work was supported by the Health Research Council of New Zealand's International Investment Opportunities Fund (IIOF 09_04 to W.P.T., J.P.P and T.SC) and co-funded by the Walter and Eliza Hall Institute and Otago Innovation Pty Ltd. The authors thank the National Health and Medical Research Council of Australia (App. 1010326 for funding B.E.S.), the Australian Cancer Research Foundation, and a Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.