Nullbasic, a potent Anti-HIV Tat mutant, induces CRM1-dependent disruption of HIV Rev trafficking

Lin, Min-Hsuan, Sivakumaran, Haran, Apolloni, Ann, Wei, Ting, Jans, David A. and Harrich, David (2012) Nullbasic, a potent Anti-HIV Tat mutant, induces CRM1-dependent disruption of HIV Rev trafficking. PloS One, 7 12: e51466-1-e51466-12. doi:10.1371/journal.pone.0051466

Author Lin, Min-Hsuan
Sivakumaran, Haran
Apolloni, Ann
Wei, Ting
Jans, David A.
Harrich, David
Title Nullbasic, a potent Anti-HIV Tat mutant, induces CRM1-dependent disruption of HIV Rev trafficking
Journal name PloS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2012-12
Sub-type Article (original research)
DOI 10.1371/journal.pone.0051466
Open Access Status DOI
Volume 7
Issue 12
Start page e51466-1
End page e51466-12
Total pages 12
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2013
Language eng
Formatted abstract
Nullbasic, a mutant of the HIV-1 Tat protein, has anti-HIV-1 activity through mechanisms that include inhibition of Rev function and redistribution of the HIV-1 Rev protein from the nucleolus to the nucleoplasm and cytoplasm. Here we investigate the mechanism of this effect for the first time, establishing that redistribution of Rev by Nullbasic is not due to direct interaction between the two proteins. Rather, Nullbasic affects subcellular localization of cellular proteins that regulate Rev trafficking. In particular, Nullbasic induced redistribution of exportin 1 (CRM1), nucleophosmin (B23) and nucleolin (C23) from the nucleolus to the nucleus when Rev was coexpressed, but never in its absence. Inhibition of the Rev:CRM1 interaction by leptomycin B or a non-interacting RevM10 mutant completely blocked redistribution of Rev by Nullbasic. Finally, Nullbasic did not inhibit importin β- or transportin 1-mediated nuclear import, suggesting that cytoplasmic accumulation of Rev was due to increased export by CRM1. Overall, our data support the conclusion that CRM1-dependent subcellular redistribution of Rev from the nucleolus by Nullbasic is not through general perturbation of either nuclear import or export. Rather, Nullbasic appears to interact with and disrupt specific components of a Rev trafficking complex required for its nucleocytoplasmic shuttling and, in particular, its nucleolar accumulation.
Keyword Immunodeficiency virus
Nucleolar protein B23
Nuclear export factor
Transdominant Tat
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Chemistry and Molecular Biosciences
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Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
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