The ability of TNPO3-depleted cells to inhibit HIV-1 infection requires CPSF6
Open Access
- 26 April 2013
- journal article
- research article
- Published by Springer Science and Business Media LLC in Retrovirology
- Vol. 10 (1), 46-14
- https://doi.org/10.1186/1742-4690-10-46
Abstract
Expression of the cellular karyopherin TNPO3/transportin-SR2/Tnp3 is necessary for HIV-1 infection. Depletion of TNPO3 expression in mammalian cells inhibits HIV-1 infection after reverse transcription but prior to integration. This work explores the role of cleavage and polyadenylation specificity factor subunit 6 (CPSF6) in the ability of TNPO3-depleted cells to inhibit HIV-1 infection. Our findings showed that depletion of TNPO3 expression inhibits HIV-1 infection, while the simultaneous depletion of TNPO3 and CPSF6 expression rescues HIV-1 infection. Several experiments to understand the rescue of infectivity by CPSF6 were performed. Our experiments revealed that the HIV-1 capsid binding ability of the endogenously expressed CPSF6 from TNPO3-depleted cells does not change when compared to CPSF6 from wild type cells. In agreement with our previous results, depletion of TNPO3 did not change the nuclear localization of CPSF6. Studies on the formation of 2-LRT circles during HIV-1 infection revealed that TNPO3-depleted cells are impaired in the integration process or exhibit a defect in the formation of 2-LTR circles. To understand whether the cytosolic fraction of CPSF6 is responsible for the inhibition of HIV-1 in TNPO3-depleted cells, we tested the ability of a cytosolic full-length CPSF6 to block HIV-1 infection. These results demonstrated that overexpression of a cytosolic full-length CPSF6 blocks HIV-1 infection at the nuclear import step. Fate of the capsid assays revealed that cytosolic expression of CPSF6 enhances stability of the HIV-1 core during infection. These results suggested that inhibition of HIV-1 by TNPO3-depleted cells requires CPSF6.Keywords
This publication has 28 references indexed in Scilit:
- TNPO3 Is Required for HIV-1 Replication after Nuclear Import but prior to Integration and Binds the HIV-1 CoreJournal of Virology, 2012
- HIV-1 Capsid-Targeting Domain of Cleavage and Polyadenylation Specificity Factor 6Journal of Virology, 2012
- The Cargo-Binding Domain of Transportin 3 Is Required for Lentivirus Nuclear ImportJournal of Virology, 2011
- Contribution of E3-Ubiquitin Ligase Activity to HIV-1 Restriction by TRIM5α rh : Structure of the RING Domain of TRIM5αJournal of Virology, 2011
- Small-Molecule Inhibition of Human Immunodeficiency Virus Type 1 Infection by Virus Capsid DestabilizationJournal of Virology, 2011
- Flexible Use of Nuclear Import Pathways by HIV-1Cell Host & Microbe, 2010
- The Requirement for Cellular Transportin 3 (TNPO3 or TRN-SR2) during Infection Maps to Human Immunodeficiency Virus Type 1 Capsid and Not IntegraseJournal of Virology, 2010
- Global Analysis of Host-Pathogen Interactions that Regulate Early-Stage HIV-1 ReplicationCell, 2008
- A human TRIM5α B30.2/SPRY domain mutant gains the ability to restrict and prematurely uncoat B-tropic murine leukemia virusVirology, 2008
- Identification of Host Proteins Required for HIV Infection Through a Functional Genomic ScreenScience, 2008