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    Prototypical Recombinant Multi-Protease Inhibitor Resistant Infectious Molecular Clones of Human Immunodeficiency Virus Type-1

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    Authors
    Varghese, Vici
    Mitsuya, Yumi
    Fessel, W. Jeffrey
    Liu, Tommy F.
    Melikian, George L.
    Katzenstein, David A.
    Schiffer, Celia A.
    Holmes, Susan P.
    Shafer, Robert W.
    UMass Chan Affiliations
    Department of Biochemistry and Molecular Pharmacology
    Document Type
    Journal Article
    Publication Date
    2013-06-24
    Keywords
    Biochemistry
    Chemicals and Drugs
    Molecular Biology
    Therapeutics
    Virology
    Virus Diseases
    
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    Link to Full Text
    http://dx.doi.org/10.1128/AAC.00614-13
    Abstract
    The many genetic manifestations of HIV-1 protease inhibitor (PI) resistance present challenges to research into the mechanisms of PI-resistance and the assessment of new PIs. To address these challenges, we created a panel of recombinant multi-PI resistant infectious molecular clones designed to represent the spectrum of clinically relevant multi-PI resistant viruses. To assess the representativeness of this panel, we examined the sequences of the panel's viruses in the context of a correlation network of PI-resistance amino acid substitutions in sequences from more than 10,000 patients. The panel of recombinant infectious molecular clones comprised 29 of 41 study-defined PI-resistance amino acid substitutions and 23 of the 27 tightest amino acid substitution clusters. Based on their phenotypic properties, the clones were classified into four groups with increasing cross-resistance to the PIs most commonly used for salvage therapy: lopinavir (LPV), tipranavir (TPV), and darunavir (DRV). The panel of recombinant infectious molecular clones has been made available without restriction through the NIH AIDS Research and Reference Reagent Program. The public availability of the panel makes it possible to compare the inhibitory activity of different PIs with one another. The diversity of the panel and the high-level PI resistance of its clones suggest that investigational PIs active against the clones in this panel will retain antiviral activity against most, if not all clinically relevant PI-resistant viruses.
    Source
    Antimicrob Agents Chemother. 2013 Jun 24. Link to article on publisher's site
    DOI
    10.1128/AAC.00614-13
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/26078
    PubMed ID
    23796938
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1128/AAC.00614-13
    Scopus Count
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    UMass Chan Faculty and Researcher Publications
    Schiffer Lab Publications

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