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Title: Mutations in the catalytic core or the C-terminus of murine leukemia virus (MLV) integrase disrupt virion infectivity and exert diverse effects on reverse transcription

Abstract

Understanding of the structures and functions of the retroviral integrase (IN), a key enzyme in the viral replication cycle, is essential for developing antiretroviral treatments and facilitating the development of safer gene therapy vehicles. Thus, four MLV IN-mutants were constructed in the context of a retroviral vector system, harbouring either a substitution in the catalytic centre, deletions in the C-terminus, or combinations of both modifications. IN-mutants were tested for their performance in different stages of the viral replication cycle: RNA-packaging; RT-activity; transient and stable infection efficiency; dynamics of reverse transcription and nuclear entry. All mutant vectors packaged viral RNA with wild-type efficiencies and displayed only slight reductions in RT-activity. Deletion of either the IN C-terminus alone, or in addition to part of the catalytic domain exerted contrasting effects on intracellular viral DNA levels, implying that IN influences reverse transcription in more than one direction.

Authors:
 [1];  [1];  [1];  [1];  [2];  [3]
  1. Research Institute for Virology and Biomedicine, University of Veterinary Medicine, A-1210 Vienna (Austria)
  2. Austrianova Biotechnology GmbH, A-1210 Vienna (Austria)
  3. Research Institute for Virology and Biomedicine, University of Veterinary Medicine, A-1210 Vienna (Austria). E-mail: dieter.klein@vu-wien.ac.at
Publication Date:
OSTI Identifier:
20977024
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 362; Journal Issue: 1; Other Information: DOI: 10.1016/j.virol.2006.11.037; PII: S0042-6822(06)00918-4; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; DNA; ENZYMES; GENE THERAPY; INFECTIVITY; LEUKEMIA VIRUSES; MUTANTS; POLYMERASE CHAIN REACTION; RNA; TRANSCRIPTION

Citation Formats

Steinrigl, Adolf, Nosek, Dagmara, Ertl, Reinhard, Guenzburg, Walter H., Salmons, Brian, and Klein, Dieter. Mutations in the catalytic core or the C-terminus of murine leukemia virus (MLV) integrase disrupt virion infectivity and exert diverse effects on reverse transcription. United States: N. p., 2007. Web. doi:10.1016/j.virol.2006.11.037.
Steinrigl, Adolf, Nosek, Dagmara, Ertl, Reinhard, Guenzburg, Walter H., Salmons, Brian, & Klein, Dieter. Mutations in the catalytic core or the C-terminus of murine leukemia virus (MLV) integrase disrupt virion infectivity and exert diverse effects on reverse transcription. United States. doi:10.1016/j.virol.2006.11.037.
Steinrigl, Adolf, Nosek, Dagmara, Ertl, Reinhard, Guenzburg, Walter H., Salmons, Brian, and Klein, Dieter. Fri . "Mutations in the catalytic core or the C-terminus of murine leukemia virus (MLV) integrase disrupt virion infectivity and exert diverse effects on reverse transcription". United States. doi:10.1016/j.virol.2006.11.037.
@article{osti_20977024,
title = {Mutations in the catalytic core or the C-terminus of murine leukemia virus (MLV) integrase disrupt virion infectivity and exert diverse effects on reverse transcription},
author = {Steinrigl, Adolf and Nosek, Dagmara and Ertl, Reinhard and Guenzburg, Walter H. and Salmons, Brian and Klein, Dieter},
abstractNote = {Understanding of the structures and functions of the retroviral integrase (IN), a key enzyme in the viral replication cycle, is essential for developing antiretroviral treatments and facilitating the development of safer gene therapy vehicles. Thus, four MLV IN-mutants were constructed in the context of a retroviral vector system, harbouring either a substitution in the catalytic centre, deletions in the C-terminus, or combinations of both modifications. IN-mutants were tested for their performance in different stages of the viral replication cycle: RNA-packaging; RT-activity; transient and stable infection efficiency; dynamics of reverse transcription and nuclear entry. All mutant vectors packaged viral RNA with wild-type efficiencies and displayed only slight reductions in RT-activity. Deletion of either the IN C-terminus alone, or in addition to part of the catalytic domain exerted contrasting effects on intracellular viral DNA levels, implying that IN influences reverse transcription in more than one direction.},
doi = {10.1016/j.virol.2006.11.037},
journal = {Virology},
number = 1,
volume = 362,
place = {United States},
year = {Fri May 25 00:00:00 EDT 2007},
month = {Fri May 25 00:00:00 EDT 2007}
}