       Document 0029
 DOCN  M9620029
 TI    K65R mutation of human immunodeficiency virus type 1 reverse
       transcriptase encodes cross-resistance to
       9-(2-phosphonylmethoxyethyl)adenine.
 DT    9602
 AU    Gu Z; Salomon H; Cherrington JM; Mulato AS; Chen MS; Yarchoan R; Foli A;
       Sogocio KM; Wainberg MA; McGill University AIDS Centre, Jewish General
       Hospital, Montreal,; Quebec, Canada.
 SO    Antimicrob Agents Chemother. 1995 Aug;39(8):1888-91. Unique Identifier :
       AIDSLINE MED/96100773
 AB    Cloned variants of human immunodeficiency virus type 1 that contain the
       K65R mutation in reverse transcriptase have previously been shown to
       display approximately 10- to 30-fold resistance against
       2',3'-dideoxycytidine, 2',3'-dideoxyinosine, and
       2',3'-dideoxy-3'-thiacytidine. On the basis of tissue culture studies
       with both primary T cells and established cell lines, we now report that
       the K65R mutation confers approximately 12- to 15-fold resistance to
       9-(2-phosphonylmethoxyethyl)adenine (PMEA). Likewise, a chain
       termination system revealed that mutated recombinant K65R reverse
       transcriptase displays resistance to PMEA diphosphate, the active
       metabolite of PMEA, in cell-free enzyme assays. Parallel studies have
       shown that the M184V mutation in reverse transcriptase, associated with
       high-level resistance against the (-) enantiomer of
       2',3'-dideoxy-3'-thiacytidine, does not confer resistance to PMEA in
       tissue culture. Viruses and enzymes that included both the K65R and
       M184V mutations were resistant to PMEA and PMEa diphosphate,
       respectively, but only to the extent conferred by the K65R mutation
       alone.
 DE    Adenine/*ANALOGS & DERIVATIVES/PHARMACOLOGY  Antiviral
       Agents/*PHARMACOLOGY  Cell-Free System  Cloning, Molecular  Drug
       Resistance, Microbial/GENETICS  Human  HIV Infections/MICROBIOLOGY
       HIV-1/*ENZYMOLOGY/*GENETICS  RNA-Directed DNA
       Polymerase/*GENETICS/*METABOLISM  Support, Non-U.S. Gov't  Tissue
       Culture  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

