Skip NavigationSkip to Content
Return Return to Search Results

HIV-1 reverse transcriptase connection subdomain mutations reduce template RNA degradation and enhance AZT excision

  1. Author:
    Delviks-Frankenberry, K. A.
    Nikolenko, G. N.
    Boyer, P. L.
    Hughes, S. H.
    Coffin, J. M.
    Jere, A.
    Pathak, V. K.

  2. Author Address

    Delviks-Frankenberry, Krista A.; Nikolenko, Galina N.; Jere, Abhay, Pathak, Vinay K.] Natl Canc Inst, HIV Drug Resistance Program, Viral Mutat Sect, Frederick, MD 21702 USA. [Boyer, Paul L.; Hughes, Stephen H.] Natl Canc Inst, HIV Drug Resistance Program, Vector Design & Replicat Sect, Frederick, MD 21702 USA. [Coffin, John M.] Natl Canc Inst, HIV Drug Resistance Program, Host Virus Interact Unit, Frederick, MD 21702 USA. [Coffin, John M.] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA.
    1. Year: 2008
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 105
    2. 31
    3. Pages: 10943-10948
  4. Type of Article: Article
  1. Abstract:

    We previously proposed that mutations in the connection subdomain (cn) of HIV-1 reverse transcriptase increase AZT resistance by altering the balance between nucleotide excision and template RNA degradation. To test the predictions of this model, we analyzed the effects of previously identified cn mutations in combination with thymidine analog mutations (D67N, K70R, T215Y, and K219Q) on in vitro RNase H activity and AZT monophosphate (AZTMP) excision. We found that cn mutations G335C/D, N348I, A360I/V, V365I, and A376S decreased primary and secondary RNase H cleavages. The patient-derived cns increased ATP- and PPi-mediated AZTMP excision on an RNA template compared with a DNA template. One of 5 cns caused an increase in ATP-mediated AZTMP excision on a DNA template, whereas three cns showed a higher ratio of ATP- to PPi-mediated excision, indicating that some cn mutations also affect excision on a DNA substrate. Overall, the results strongly support the model that cn mutations increase AZT resistance by reducing template RNA degradation, thereby providing additional time for RT to excise AZTMP.

    See More

  1. Keywords:

External Sources

  1. PMID: 18667707

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