Cyclophilin A Interacts with HIV-1 Vpr and Is Required for Its Functional Expression
| Autor: | Ulrich Schubert, Kerstin Zander, Jason Neidleman, Uwe Tessmer, Michael P. Sherman, Evelyn Schubert, Victor Wray, Karsten Bruns, Jeremy Luban, Warner C. Greene, Alexander T. Prechtel, Peter Henklein |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
G2 Phase
Time Factors Proline Protein Conformation T-Lymphocytes viruses Blotting Western Molecular Sequence Data Cypa Plasma protein binding Transfection Biochemistry Jurkat cells Jurkat Cells Cyclophilin A Protein structure Cyclosporin a Humans Amino Acid Sequence Disulfides Molecular Biology Sequence Homology Amino Acid biology Gene Products vpr virus diseases DNA Cell Biology Surface Plasmon Resonance biochemical phenomena metabolism and nutrition Blotting Northern Flow Cytometry biology.organism_classification Recombinant Proteins Protein Structure Tertiary Cell biology Viral replication HeLa Cells Plasmids Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 278:43202-43213 |
| ISSN: | 0021-9258 |
| Popis: | Viral protein R (Vpr) of human immunodeficiency virus, type 1 (HIV-1) is the major virion-associated accessory protein that affects a number of biological functions in the retroviral life cycle, including promotion of the transport of the preintegration complex into the nucleus and the induction of G2 host cell cycle arrest. Our recent investigation of the conformational heterogeneity of the proline residues in the N terminus of Vpr suggested a functional interaction between Vpr and a host peptidylprolyl cis/trans isomerase (PPIase) that might regulate the cis/trans interconversion of the imidic bond within the conserved proline residues of Vpr in vivo. Using surface plasmon resonance spectroscopy, Far Western blot, and pulldown experiments a physical interaction of Vpr with the major host PPIase cyclophilin A (CypA) is now demonstrated. The interaction domain involves the N-terminal region of Vpr including an essential role for proline in position 35. The CypA inhibitor cyclosporin A and non-immunosuppressive PPIase inhibitors such as NIM811 and sanglifehrin A block expression of Vpr without affecting pre- or post-translational events such as transcription, intracellular transport, or virus incorporation of Vpr. Similarly to CypA inhibition, Vpr expression is also reduced in HIV-1 infected CypA-/- knock-out T cells. This study thus shows that in addition to the interaction between CypA and HIV-1 capsid occurring during early steps in virus replication, CypA is also important for the de novo synthesis of Vpr and that in the absence of CypA activity, the Vpr-mediated cell cycle arrest is completely lost in HIV-1-infected T cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|