Skip NavigationSkip to Content
Return Return to Search Results

In vitro induction of human immunodeficiency virus type 1 variants resistant to phosphoralaninate prodrugs of Z-methylenecyclopropane nucleoside analogues

  1. Author:
    Yoshimura, K.
    Feldman, R.
    Kodama, E.
    Kavlick, M. F.
    Qiu, Y. L.
    Zemlicka, J.
    Mitsuya, H.

  2. Author Address

    Mitsuya H NCI, Med Branch, Experimental Retrovirol Sect, Div Clin Sci,NIH Bldg 10,Room 5A11,9000 Rockville Pk Bethesda, MD 20892 USA NCI, Med Branch, Experimental Retrovirol Sect, Div Clin Sci,NIH Bethesda, MD 20892 USA Wayne State Univ, Sch Med, Barbara Ann Karmanos Canc Inst, Dept Chem Detroit, MI 48201 USA NCI, Frederick Canc Res & Dev Ctr, SAIC, Dev Therapeut Program,HIV Clin Interface Lab Frederick, MD 21702 USA Kumamoto Univ, Sch Med, Dept Internal Med 2 Kumamoto 860 Japan
    1. Year: 1999
  2. Journal: Antimicrobial Agents and Chemotherapy
    1. 43
    2. 10
    3. Pages: 2479-2483
  4. Type of Article: Article
  1. Abstract:

    Two methylenecyclopropane nucleoside analogues with a phenylphosphoralaninate moiety, QYL-685 and QYL-609, exert potent and specific activities against human immunodeficiency virus type 1 strain LAI (HIV-1(LAI)) and HIV-2 in vitro. In this study, we induced HIV-1 variants resistant to QYL-685 by exposing HIV-1(LAI) to increasing concentrations of QYL-685, After 16 passages, the virus (HIV-1(P16)) was less sensitive to QYL-685 (104-fold), QYL-609 (>41-fold), and (-)-beta-2',3'-dideoxy-3'-thiacytidine (3TC) (>1,100-fold) than was HIV-1, and contained an M184I mutation. Two infectious clones, HIV-1(M184I) and HIV-1(M184V) were resistant to QYL-685, QYL-609, and 3TC, confirming that the M184I mutation was responsible for the observed resistance. Viral-fitness analyses (competitive HIV-1 replication assays) revealed that in the absence of drugs, R M184I and M184V conferred a replication disadvantage on the virus compared to the replication efficiency of the wild-type infectious clone (HIV-1(wt)). However, in the presence of QYL-685 (4 mu M), HIV-1(M184I) and HIV-1(M184V) showed greater fitness than HIV-1,. These data may provide structural and virological relevance with regard to the emergence of M184I and M184V substitutions in HIV-1. [References: 26]

    See More

  1. Keywords:

External Sources

  1. No sources found.

Library Notes

  1. No notes added.
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel