Inhibitors of human immunodeficiency virus type 1 reverse transcriptase target distinct phases of early reverse transcription

Hooker, C. William, Lott, William B. and Harrich, David (2001) Inhibitors of human immunodeficiency virus type 1 reverse transcriptase target distinct phases of early reverse transcription. Journal of Virology, 75 7: 3095-3104. doi:10.1128/JVI.75.7.3095-3104.2001


Author Hooker, C. William
Lott, William B.
Harrich, David
Title Inhibitors of human immunodeficiency virus type 1 reverse transcriptase target distinct phases of early reverse transcription
Journal name Journal of Virology   Check publisher's open access policy
ISSN 0022-538X
1098-5514
Publication date 2001-04
Year available 2001
Sub-type Article (original research)
DOI 10.1128/JVI.75.7.3095-3104.2001
Open Access Status DOI
Volume 75
Issue 7
Start page 3095
End page 3104
Total pages 10
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2001
Language eng
Subject C1
270303 Virology
730101 Infectious diseases
Abstract Early HIV-1 reverse transcription can be separated into initiation and elongation phases. Here we show, using PCR analysis of negative-strand strong-stop DNA [(-)ssDNA] synthesis in intact virus, that different reverse transcriptase (RT) inhibitors affect distinct phases of early natural endogenous reverse transcription (NERT), The effects of nevirapine on NERT were consistent with a mechanism of action including both specific and nonspecific binding events. The nonspecific component of this inhibition targeted the elongation reaction, whereas the specific effect seemed principally to be directed at very early events (initiation or the initiation-elongation switch), In contrast, foscarnet and the nucleoside analog ddATP inhibited both early and late (-)ssDNA synthesis in a similar manner. We also examined compounds that targeted other viral proteins and found that Ro24-7429 (a Tat antagonist) and rosmarinic acid (an integrase inhibitor) also directly inhibited RT, Our results indicate that NERT can be used to identify and evaluate compounds that directly target the reverse transcription complex.
Keyword Virology
Hiv-1 Nucleocapsid Protein
Terminal Repeat Sequences
Dependent Dna Polymerase
Viral Nucleic-acids
Strong-stop Dna
In-vitro
Secondary Structure
Nonnucleoside Inhibitors
1-infected Individuals
Nonpermissive Cells
Q-Index Code C1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
 
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Created: Tue, 14 Aug 2007, 16:06:14 EST