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'Binding, bending and bonding': polypurine tract-primed initiation of plus-strand DNA synthesis in human immunodeficiency virus

Journal

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
Volume 36, Issue 9, Pages 1752-1766

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2004.02.016

Keywords

retrovirus; plus-strand synthesis; reverse transcriptase; RNA/DNA hybrid; ribonuclease H

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During the course of reverse transcription, human immunodeficiency virus type I reverse transcriptase (HIV-1 RT) initiates plus-strand DNA synthesis from two highly conserved, purine-rich RNA segments of the viral genome referred to as the 3' and central polypurine tracts (3' and cPPTs). Processing of these elements occurs in several sequential steps including (1) minus-strand DNA synthesis over the PPT(s), (2) ribonuclease H (RNase H) mediated cleavage at the PPT 3' terminus, (3) plus-strand DNA synthesis from the nascent RNA primer(s), and (4) primer removal. Completing each of these steps precisely and specifically is essential, as failure to do so can result in reduced virus replication and/or impaired integration of viral DNA into the host cell genome. In this review, plus-strand primer processing in HIV-1 is discussed from biochemical, structural, and historical perspectives. A comparative analysis of PPT-processing in different LTR-containing retroelements is also presented. (C) 2004 Elsevier Ltd. All rights reserved.

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