Nucleic Acids Research, Vol 26, Issue 19 4389-4394, Copyright © 1998 by Oxford University Press
ME Hamburgh, WC Drosopoulos and VR Prasad
Two nucleoside analog resistance mutations in HIV-1 reverse transcriptase
(RT), E89G and M184V, were previously shown to increase the dNTP insertion
fidelity of HIV-1 RT. However, forward mutation assays using a lacZ alpha
reporter gene have revealed a lack of impact on the overall error rate of
these variants. In an effort to investigate the basis for this discrepancy,
we have examined whether the increases in misinsertion fidelity observed
for E89G and M184V RTs are accompanied by an increase in mispair extension
fidelity. The relative efficiencies with which the wild type, E89G, M184V
and M184V/E89G HIV-1 RTs extend model template-primer duplexes containing
3'-OH terminal mismatches were measured. The calculated efficiencies of
mispair extension ( f ext) were, in general, not significantly decreased
from the wild type HIV-1 RT. In fact, the efficiency of extension from one
of the mispaired primer-template duplexes was significantly increased for
two of the mutants tested. These results suggest that amino acid
substitutions that increase the fidelity of dNTP insertion do not
necessarily increase misextension fidelity, and that the decreased
misextension fidelity may counterbalance the increases in misinsertion
fidelity observed for E89G and M184V RTs.
ARTICLES
The influence of 3TC-resistance mutations E89G and M184V in the human immunodeficiency virus reverse transcriptase on mispair extension efficiency
Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Skasko, K. K. Weiss, H. M. Reynolds, V. Jamburuthugoda, K. Lee, and B. Kim Mechanistic Differences in RNA-dependent DNA Polymerization and Fidelity between Murine Leukemia Virus and HIV-1 Reverse Transcriptases J. Biol. Chem., April 1, 2005; 280(13): 12190 - 12200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. K. Halvas, E. S. Svarovskaia, and V. K. Pathak Development of an In Vivo Assay To Identify Structural Determinants in Murine Leukemia Virus Reverse Transcriptase Important for Fidelity J. Virol., January 1, 2000; 74(1): 312 - 319. [Abstract] [Full Text]
|
|
|
|
|
|
F. S. Shah, K. A. Curr, M. E. Hamburgh, M. Parniak, H. Mitsuya, J. G. Arnez, and V. R. Prasad Differential Influence of Nucleoside Analog-resistance Mutations K65R and L74V on the Overall Mutation Rate and Error Specificity of Human Immunodeficiency Virus Type 1 Reverse Transcriptase J. Biol. Chem., August 25, 2000; 275(35): 27037 - 27044. [Abstract] [Full Text] [PDF]
|
|