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Nullbasic, a Potent Anti-HIV Tat Mutant, Induces CRM1-Dependent Disruption of HIV Rev Trafficking
- Source :
- PLoS ONE, PLoS ONE, Vol 7, Iss 12, p e51466 (2012)
- Publication Year :
- 2012
- Publisher :
- Public Library of Science (PLoS), 2012.
-
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.
- Subjects :
- Anatomy and Physiology
Nucleolus
Chromosomal Proteins, Non-Histone
viruses
Receptors, Cytoplasmic and Nuclear
environment and public health
Immunodeficiency Viruses
Molecular Cell Biology
Nuclear protein
Multidisciplinary
Nuclear Proteins
RNA-Binding Proteins
Obstetrics and Gynecology
beta Karyopherins
Cellular Structures
Cell biology
Protein Transport
Medicine
Infectious diseases
Beta Karyopherins
tat Gene Products, Human Immunodeficiency Virus
Nucleophosmin
Cell Nucleolus
Protein Binding
Subcellular Fractions
Research Article
Cell Physiology
Anti-HIV Agents
Science
Urology
Retrovirology and HIV immunopathogenesis
Importin
Viral diseases
Biology
Karyopherins
Microbiology
Virology
Humans
Nucleoplasm
Genitourinary Infections
HIV
rev Gene Products, Human Immunodeficiency Virus
Subcellular localization
Phosphoproteins
Molecular biology
Viral Replication
HEK293 Cells
Subcellular Organelles
HIV-1
Mutant Proteins
Nuclear transport
Nucleolin
HeLa Cells
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 7
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....34152b99e7eea5ba8832d0ed59dbf1e2
- Full Text :
- https://doi.org/10.1371/journal.pone.0051466