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| Content Provider | PubMed Central |
|---|---|
| Author | Misumi, Shogo Inoue, Mutsumi Dochi, Takeo Kishimoto, Naoki Hasegawa, Naomi Nobutoki, Takamune Shoji, Shozo |
| Abstract | The process by which the human immunodeficiency virus type 1 (HIV-1) conical core dissociates is called uncoating, but not much is known about this process. Here, we show that the uncoating process requires the interaction of the capsid (CA) protein with the peptidyl-prolyl isomerase Pin1 that specifically recognizes the phosphorylated serine/threonine residue followed by proline. We found that the HIV-1 core is composed of some isoforms of the CA protein with different isoelectric points, and one isoform is preferentially phosphorylated in the Ser16-Pro17 motif. The mutant virus S16A/P17A shows a severely attenuated HIV-1 replication and an impaired reverse transcription. The S16A/P17A change increased the amount of particulate CA cores in the cytosol of target cells and correlated with the restriction of HIV-1 infection. Glutathione S-transferase pulldown assays demonstrated a direct interaction between Pin1 and the HIV-1 core via the Ser16-Pro17 motif. Suppression of Pin1 expression by RNA interference in a target cell results in an attenuated HIV-1 replication and increases the amount of particulate CA cores in the cytosol of target cells. Furthermore, heat-inactivated, inhibitor-treated, or W34A/K63A Pin1 causes an attenuated in vitro uncoating of the HIV-1 core. The Pin1-dependent uncoating is inhibited by antisera raised against a CA peptide phosphorylated at Ser16 or treatment of the HIV-1 core with alkaline phosphatase. These findings provide insights into this obscure uncoating process in the HIV-1 life cycle and a new cellular target for HIV-1 drug development. |
| Related Links | http://dx.doi.org/10.1074/jbc.M110.114256 |
| Ending Page | 25195 |
| Page Count | 11 |
| Starting Page | 25185 |
| File Format | |
| ISSN | 1083351X |
| e-ISSN | 1083351X |
| Journal | The Journal of Biological Chemistry |
| Issue Number | 33 |
| Volume Number | 285 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 2010-08-13 |
| Access Restriction | Open |
| Rights Holder | American Society for Biochemistry and Molecular Biology |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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