Potent inhibition of HIV-1 replication by a tat mutant

Meredith, Luke W., Sivakumaran, Haran, Major, Lee, Suhrbier, Andreas and Harrich, David (2009) Potent inhibition of HIV-1 replication by a tat mutant. PloS One, 4 11: e7769.1-e7769.10. doi:10.1371/journal.pone.0007769

Author Meredith, Luke W.
Sivakumaran, Haran
Major, Lee
Suhrbier, Andreas
Harrich, David
Title Potent inhibition of HIV-1 replication by a tat mutant
Journal name PloS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2009-11-10
Year available 2009
Sub-type Article (original research)
DOI 10.1371/journal.pone.0007769
Open Access Status DOI
Volume 4
Issue 11
Start page e7769.1
End page e7769.10
Total pages 11
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Collection year 2010
Language eng
Subject 1100 Agricultural and Biological Sciences
1300 Biochemistry, Genetics and Molecular Biology
2700 Medicine
Abstract Herein we describe a mutant of the two-exon HIV-1 Tat protein, termed Nullbasic, that potently inhibits multiple steps of the HIV-1 replication cycle. Nullbasic was created by replacing the entire arginine-rich basic domain of wild type Tat with glycine/alanine residues. Like similarly mutated one-exon Tat mutants, Nullbasic exhibited transdominant negative effects on Tat-dependent transactivation. However, unlike previously reported mutants, we discovered that Nullbasic also strongly suppressed the expression of unspliced and singly-spliced viral mRNA, an activity likely caused by redistribution and thus functional inhibition of HIV-1 Rev. Furthermore, HIV-1 virion particles produced by cells expressing Nullbasic had severely reduced infectivity, a defect attributable to a reduced ability of the virions to undergo reverse transcription. Combination of these inhibitory effects on transactivation, Rev-dependent mRNA transport and reverse transcription meant that permissive cells constitutively expressing Nullbasic were highly resistant to a spreading infection by HIV-1. Nullbasic and its activities thus provide potential insights into the development of potent antiviral therapeutics that target multiple stages of HIV-1 infection.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Public Health Publications
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