Association of a novel human immunodeficiency virus type 1 protease substrate cleft mutation, L23I, with protease inhibitor therapy and in vitro drug resistance
Department of Biochemistry and Molecular Pharmacology
Medical Subject Headings
Drug Resistance, Viral; HIV Infections; HIV Protease; HIV Protease Inhibitors; HIV-1; Humans; Models, Molecular; Mutation; Oligopeptides; Protein Conformation
We observed a previously uncharacterized mutation in the protease substrate cleft, L23I, in 31 of 4,303 persons undergoing human immunodeficiency virus type 1 genotypic resistance testing. In combination with V82I, L23I was associated with a sevenfold reduction in nelfinavir susceptibility and a decrease in replication capacity. In combination with other drug resistance mutations, L23I was associated with multidrug resistance and a compensatory increase in replication capacity.
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Citation: Antimicrob Agents Chemother. 2004 Dec;48(12):4864-8. Link to article on publisher's site
Johnston, Elizabeth; Winters, Mark A.; Rhee, Soo-Yon; Merigan, Thomas C.; Schiffer, Celia A.; and Shafer, Robert W., "Association of a novel human immunodeficiency virus type 1 protease substrate cleft mutation, L23I, with protease inhibitor therapy and in vitro drug resistance" (2004). Biochemistry and Molecular Pharmacology Publications and Presentations. Paper 81.