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Wild-type and YMDD mutant murine leukemia virus reverse transcriptases are resistant to 2 ',3 '-dideoxy-3 '-thiacytidine

  1. Author:
    Halvas, E. K.
    Svarovskaia, E. S.
    Freed, E. O.
    Pathak, V. K.

  2. Author Address

    Pathak VK NCI, HIV Drug Resistance Program, Frederick Canc Res & Dev Ctr Bldg 535,Rm 334 Frederick, MD 21702 USA NCI, HIV Drug Resistance Program, Frederick Canc Res & Dev Ctr Frederick, MD 21702 USA W Virginia Univ, Mary Babb Randolph Canc Ctr Morgantown, WV 26506 USA W Virginia Univ, Dept Biochem Morgantown, WV 26506 USA NIAID, Mol Microbiol Lab, NIH Bethesda, MD 20892 USA
    1. Year: 2000
  2. Journal: Journal of Virology
    1. 74
    2. 14
    3. Pages: 6669-6674
  4. Type of Article: Article
  1. Abstract:

    The antiretroviral nucleoside analog 2',3'-dideoxy-3'-thiacytidine (3TC) is a potent inhibitor of wild-type human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), A methionine-to-valine or methionine-to-isoleucine substitution at residue 184 in the HIV-1 YMDD motif, which is located at the RT active site, leads to a high level of resistance to 3TC. We sought to determine whether 3TC can inhibit the replication of wild-type murine leukemia virus (MLV), which contains V223 at the YVDD active site motif of the MLV RT, and of the V223M, V223I, V223A, and V223S mutant RTs. Surprisingly, the wild type and all four of the V223 mutants of MLV RT were highly resistant to 3TC. These results indicate that determinants outside the YVDD motif of MLV RT confer a high level of resistance to 3TC. Therefore, structural differences among similar RTs might result in widely divergent sensitivities to antiretroviral nucleoside analogs. [References: 55]

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