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Mutations at position 184 of human immunodeficiency virus type-1 reverse transcriptase affect virus titer and viral DNA synthesis

  1. Author:
    Julias, J. G.
    Boyer, P. L.
    McWilliams, M. J.
    Alvord, W. G.
    Hughes, S. H.
  2. Author Address

    Hughes, SH, NCI Frederick, HIV Drug Resistance Program, POB B,Bldg 539,Room 130A, Frederick, MD 21702 USA NCI Frederick, HIV Drug Resistance Program, Frederick, MD 21702 USA. SAIC Frederick Inc, Basic Res Program, NCI Frederick, Frederick, MD 21702 USA. NCI Frederick, Data Management Serv, Frederick, MD 21702 USA.
    1. Year: 2004
  1. Journal: Virology
    1. 322
    2. 1
    3. Pages: 13-21
  2. Type of Article: Article
  1. Abstract:

    Methionine at position 184 of human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT) was changed to valine, isoleucine, threonine, or alanine in an HIV-1-based vector. The vectors were analyzed for replication capacity and for resistance to the nucleoside analog 2',3'-dideoxy-3thiacytidine (3TC) using a single-cycle assay. Viruses containing the valine or isoleucine mutations were highly resistant to 3TC and replicated almost as well as the wild-type virus. The virus containing the threonine mutation was resistant to 3TC, but replicated about 30% as well as the wild-type. The alanine mutation conferred partial resistance to 3TC, but replicated poorly. The amounts of viral DNA synthesized decreased in 3TC-treated cells when the cells were infected with wild-type virus and the M184A mutant. The effect of these mutations on the generation of the ends of the linear viral DNA was determined using the sequence of the 2-LTR circle junctions. The M184T mutation increased the proportion of 2-LTR circle junctions containing a tRNA insertion, suggesting that the mutation affected the RNase H activity of RT. (C) 2004 Elsevier Inc. All rights reserved

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