CRL4-DCAF1 Ubiquitin Ligase Dependent Functions of HIV Viral Protein R and Viral Protein X
Abstract
:1. Introduction
1.1. Ubiquitination
1.2. Cullin-RING-E3 Ubiquitin Ligases (CRLs)
1.3. Viruses and CRL Complexes
1.4. HIV Viral Protein R (Vpr) and Viral Protein X (Vpx)
1.5. The Aim of This Work
2. The CRL4-DCAF1 E3 Ubiquitin Ligase Complex
2.1. Key Components of CRL4-DCAF1
2.2. Physiological Roles of CRL4-DCAF1
3. CRL4-DCAF1 and HIV Viral Protein R
3.1. Vpr, CRL4-DCAF1, and Target Protein Interactions
3.2. Targets Associated with G2 Cell Cycle Arrest
3.3. Targets Associated with the DNA Damage Response/DNA Repair
3.4. Targets Associated with Myeloid Cell Infection
3.5. Targets Associated with HIV or Host Cell Gene Expression
3.6. Other Targets
4. CRL4-DCAF1 and HIV-2 Viral Protein X
4.1. Vpx, CRL4-DCAF1, and Target Protein Interactions
4.2. Vpx and SAMHD1
4.3. Vpx and the HuSH Complex
4.4. Vpx and APBOBEC3A
5. Discussion—Themes and Questions
5.1. The CRL4-DCAF1 Complex Is Complex
5.2. Taking Advantage of DCAF1′s Moonlighting
5.3. The Benefits of Getting to Know Your Neighbors
5.4. A Macrophage Is Not a Macrophage Is Not a Macrophage
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Swatek, K.N.; Komander, D. Ubiquitin Modifications. Cell Res. 2016, 26, 399–422. [Google Scholar] [CrossRef] [PubMed]
- Schulman, B.A.; Harper, J.W. Ubiquitin-like Protein Activation by E1 Enzymes: The Apex for Downstream Signalling Pathways. Nat. Rev. Mol. Cell Biol. 2009, 10, 319–331. [Google Scholar] [CrossRef] [PubMed]
- Stewart, M.D.; Ritterhoff, T.; Klevit, R.E.; Brzovic, P.S. E2 Enzymes: More than Just Middle Men. Cell Res. 2016, 26, 423–440. [Google Scholar] [CrossRef] [PubMed]
- Yang, Q.; Zhao, J.; Chen, D.; Wang, Y. E3 Ubiquitin Ligases: Styles, Structures and Functions. Mol. Biomed. 2021, 2, 23. [Google Scholar] [CrossRef] [PubMed]
- Rusnac, D.-V.; Zheng, N. Structural Biology of CRL Ubiquitin Ligases. In Cullin-RING Ligases and Protein Neddylation; Advances in Experimental Medicine and Biology; Springer: Singapore, 2020; Volume 1217, pp. 9–31. [Google Scholar] [CrossRef]
- Zheng, N.; Schulman, B.A.; Song, L.; Miller, J.J.; Jeffrey, P.D.; Wang, P.; Chu, C.; Koepp, D.M.; Elledge, S.J.; Pagano, M.; et al. Structure of the Cul1-Rbx1-Skp1-F BoxSkp2 SCF Ubiquitin Ligase Complex. Nature 2002, 416, 703–709. [Google Scholar] [CrossRef] [PubMed]
- Skowyra, D.; Craig, K.L.; Tyers, M.; Elledge, S.J.; Harper, J.W. F-Box Proteins Are Receptors That Recruit Phosphorylated Substrates to the SCF Ubiquitin-Ligase Complex. Cell 1997, 91, 209–219. [Google Scholar] [CrossRef] [PubMed]
- Jin, J.; Cardozo, T.; Lovering, R.C.; Elledge, S.J.; Pagano, M.; Harper, J.W. Systematic Analysis and Nomenclature of Mammalian F-Box Proteins. Genes Dev. 2004, 18, 2573–2580. [Google Scholar] [CrossRef]
- Elliott, J.; Lynch, O.T.; Suessmuth, Y.; Qian, P.; Boyd, C.R.; Burrows, J.F.; Buick, R.; Stevenson, N.J.; Touzelet, O.; Gadina, M.; et al. Respiratory Syncytial Virus NS1 Protein Degrades STAT2 by Using the Elongin-Cullin E3 Ligase. J. Virol. 2007, 81, 3428–3436. [Google Scholar] [CrossRef]
- Yim, E.-K.; Park, J.-S. The Role of HPV E6 and E7 Oncoproteins in HPV-Associated Cervical Carcinogenesis. Cancer Res. Treat. 2005, 37, 319–324. [Google Scholar] [CrossRef]
- Murphy, C.M.; Xu, Y.; Li, F.; Nio, K.; Reszka-Blanco, N.; Li, X.; Wu, Y.; Yu, Y.; Xiong, Y.; Su, L. Hepatitis B Virus X Protein Promotes Degradation of SMC5/6 to Enhance HBV Replication. Cell Rep. 2016, 16, 2846–2854. [Google Scholar] [CrossRef]
- Ding, S.; Mooney, N.; Li, B.; Kelly, M.R.; Feng, N.; Loktev, A.V.; Sen, A.; Patton, J.T.; Jackson, P.K.; Greenberg, H.B. Comparative Proteomics Reveals Strain-Specific β-TrCP Degradation via Rotavirus NSP1 Hijacking a Host Cullin-3-Rbx1 Complex. PLoS Pathog. 2016, 12, e1005929. [Google Scholar] [CrossRef] [PubMed]
- Chen, Z.J. Ubiquitin Signalling in the NF-KappaB Pathway. Nat. Cell Biol. 2005, 7, 758–765. [Google Scholar] [CrossRef] [PubMed]
- Stavrou, S.; Ross, S.R. APOBEC3 Proteins in Viral Immunity. J. Immunol. 2015, 195, 4565–4570. [Google Scholar] [CrossRef] [PubMed]
- Volcic, M.; Wiesmüller, L.; Kirchhoff, F. Small but Highly Versatile: The Viral Accessory Protein Vpu. Annu. Rev. Virol. 2023, 10, 243–259. [Google Scholar] [CrossRef] [PubMed]
- Planelles, V.; Barker, E. Roles of Vpr and Vpx in Modulating the Virus-Host Cell Relationship. Mol. Asp. Med. 2010, 31, 398–406. [Google Scholar] [CrossRef] [PubMed]
- Ayinde, D.; Maudet, C.; Transy, C.; Margottin-Goguet, F. Limelight on Two HIV/SIV Accessory Proteins in Macrophage Infection: Is Vpx Overshadowing Vpr? Retrovirology 2010, 7, 35. [Google Scholar] [CrossRef] [PubMed]
- Casey, L.; Wen, X.; de Noronha, C.M. The Functions of the HIV1 Protein Vpr and Its Action through the DCAF1.DDB1.Cullin4 Ubiquitin Ligase. Cytokine 2010, 51, 1–9. [Google Scholar] [CrossRef]
- Sharifi, H.J.; Furuya, A.M.; de Noronha, C.M. The Role of HIV-1 Vpr in Promoting the Infection of Nondividing Cells and in Cell Cycle Arrest. Curr. Opin. HIV AIDS 2012, 7, 187–194. [Google Scholar] [CrossRef]
- Mashiba, M.; Collins, K.L. Molecular Mechanisms of HIV Immune Evasion of the Innate Immune Response in Myeloid Cells. Viruses 2012, 5, 1–14. [Google Scholar] [CrossRef]
- Guenzel, C.A.; Hérate, C.; Benichou, S. HIV-1 Vpr-a Still ‘Enigmatic Multitasker’. Front. Microbiol. 2014, 5, 127. [Google Scholar] [CrossRef]
- González, M.E. The HIV-1 Vpr Protein: A Multifaceted Target for Therapeutic Intervention. Int. J. Mol. Sci. 2017, 18, 126. [Google Scholar] [CrossRef] [PubMed]
- Beaumont, T.; van Nuenen, A.; Broersen, S.; Blattner, W.A.; Lukashov, V.V.; Schuitemaker, H. Reversal of Human Immunodeficiency Virus Type 1 IIIB to a Neutralization-Resistant Phenotype in an Accidentally Infected Laboratory Worker with a Progressive Clinical Course. J. Virol. 2001, 75, 2246–2252. [Google Scholar] [CrossRef] [PubMed]
- Tzitzivacos, D.B.; Tiemessen, C.T.; Stevens, W.S.; Papathanasopoulos, M.A. Viral Genetic Determinants of Nonprogressive HIV Type 1 Subtype C Infection in Antiretroviral Drug-Naive Children. AIDS Res. Hum. Retroviruses 2009, 25, 1141–1148. [Google Scholar] [CrossRef] [PubMed]
- Tristem, M.; Marshall, C.; Karpas, A.; Hill, F. Evolution of the Primate Lentiviruses: Evidence from Vpx and Vpr. EMBO J. 1992, 11, 3405–3412. [Google Scholar] [CrossRef] [PubMed]
- Hofmann, S.; Dehn, S.; Businger, R.; Bolduan, S.; Schneider, M.; Debyser, Z.; Brack-Werner, R.; Schindler, M. Dual Role of the Chromatin-Binding Factor PHF13 in the Pre- and Post-Integration Phases of HIV-1 Replication. Open Biol. 2017, 7, 170115. [Google Scholar] [CrossRef] [PubMed]
- Su, J.; Rui, Y.; Lou, M.; Yin, L.; Xiong, H.; Zhou, Z.; Shen, S.; Chen, T.; Zhang, Z.; Zhao, N.; et al. HIV-2/SIV Vpx Targets a Novel Functional Domain of STING to Selectively Inhibit CGAS-STING-Mediated NF-ΚB Signalling. Nat. Microbiol. 2019, 4, 2552–2564. [Google Scholar] [CrossRef] [PubMed]
- Fink, D.L.; Cai, J.; Whelan, M.V.X.; Monit, C.; Maluquer de Motes, C.; Towers, G.J.; Sumner, R.P. HIV-2/SIV Vpx Antagonises NF-ΚB Activation by Targeting P65. Retrovirology 2022, 19, 2. [Google Scholar] [CrossRef] [PubMed]
- Hannah, J.; Zhou, P. Distinct and Overlapping Functions of the Cullin E3 Ligase Scaffolding Proteins CUL4A and CUL4B. Gene 2015, 573, 33–45. [Google Scholar] [CrossRef] [PubMed]
- Sharifi, H.J.; Furuya, A.K.M.; Jellinger, R.M.; Nekorchuk, M.D.; de Noronha, C.M.C. Cullin4A and Cullin4B Are Interchangeable for HIV Vpr and Vpx Action through the CRL4 Ubiquitin Ligase Complex. J. Virol. 2014, 88, 6944–6958. [Google Scholar] [CrossRef]
- Lee, J.; Zhou, P. DCAFs, the Missing Link of the CUL4-DDB1 Ubiquitin Ligase. Mol. Cell 2007, 26, 775–780. [Google Scholar] [CrossRef]
- Schabla, N.M.; Mondal, K.; Swanson, P.C. DCAF1 (VprBP): Emerging Physiological Roles for a Unique Dual-Service E3 Ubiquitin Ligase Substrate Receptor. J. Mol. Cell Biol. 2019, 11, 725–735. [Google Scholar] [CrossRef] [PubMed]
- Wu, K.; Chen, A.; Tan, P.; Pan, Z.-Q. The Nedd8-Conjugated ROC1-CUL1 Core Ubiquitin Ligase Utilizes Nedd8 Charged Surface Residues for Efficient Polyubiquitin Chain Assembly Catalyzed by Cdc34. J. Biol. Chem. 2002, 277, 516–527. [Google Scholar] [CrossRef]
- Duda, D.M.; Borg, L.A.; Scott, D.C.; Hunt, H.W.; Hammel, M.; Schulman, B.A. Structural Insights into NEDD8 Activation of Cullin-RING Ligases: Conformational Control of Conjugation. Cell 2008, 134, 995–1006. [Google Scholar] [CrossRef]
- Wang, K.; Deshaies, R.J.; Liu, X. Assembly and Regulation of CRL Ubiquitin Ligases. Adv. Exp. Med. Biol. 2020, 1217, 33–46. [Google Scholar] [CrossRef]
- Nekorchuk, M.D.; Sharifi, H.J.; Furuya, A.K.; Jellinger, R.; de Noronha, C.M. HIV Relies on Neddylation for Ubiquitin Ligase-Mediated Functions. Retrovirology 2013, 10, 138. [Google Scholar] [CrossRef]
- Wei, W.; Guo, H.; Liu, X.; Zhang, H.; Qian, L.; Luo, K.; Markham, R.B.; Yu, X.-F. A First-in-Class NAE Inhibitor, MLN4924, Blocks Lentiviral Infection in Myeloid Cells by Disrupting Neddylation-Dependent Vpx-Mediated SAMHD1 Degradation. J. Virol. 2014, 88, 745–751. [Google Scholar] [CrossRef]
- Hofmann, H.; Norton, T.D.; Schultz, M.L.; Polsky, S.B.; Sunseri, N.; Landau, N.R. Inhibition of CUL4A Neddylation Causes a Reversible Block to SAMHD1-Mediated Restriction of HIV-1. J. Virol. 2013, 87, 11741–11750. [Google Scholar] [CrossRef] [PubMed]
- Ahn, J.; Novince, Z.; Concel, J.; Byeon, C.-H.; Makhov, A.M.; Byeon, I.-J.L.; Zhang, P.; Gronenborn, A.M. The Cullin-RING E3 Ubiquitin Ligase CRL4-DCAF1 Complex Dimerizes via a Short Helical Region in DCAF1. Biochemistry 2011, 50, 1359–1367. [Google Scholar] [CrossRef]
- Mohamed, W.I.; Schenk, A.D.; Kempf, G.; Cavadini, S.; Basters, A.; Potenza, A.; Abdul Rahman, W.; Rabl, J.; Reichermeier, K.; Thomä, N.H. The CRL4 DCAF1 Cullin-RING Ubiquitin Ligase Is Activated Following a Switch in Oligomerization State. EMBO J. 2021, 40, e108008. [Google Scholar] [CrossRef]
- Guerrero-Santoro, J.; Kapetanaki, M.G.; Hsieh, C.L.; Gorbachinsky, I.; Levine, A.S.; Rapić-Otrin, V. The Cullin 4B-Based UV-Damaged DNA-Binding Protein Ligase Binds to UV-Damaged Chromatin and Ubiquitinates Histone H2A. Cancer Res. 2008, 68, 5014–5022. [Google Scholar] [CrossRef] [PubMed]
- Bennett, E.J.; Rush, J.; Gygi, S.P.; Harper, J.W. Dynamics of Cullin-RING Ubiquitin Ligase Network Revealed by Systematic Quantitative Proteomics. Cell 2010, 143, 951–965. [Google Scholar] [CrossRef] [PubMed]
- Zhou, Z.; Song, X.; Wavelet, C.M.; Wan, Y. Cullin 4-DCAF Proteins in Tumorigenesis. Adv. Exp. Med. Biol. 2020, 1217, 241–259. [Google Scholar] [CrossRef] [PubMed]
- Cang, Y.; Zhang, J.; Nicholas, S.A.; Bastien, J.; Li, B.; Zhou, P.; Goff, S.P. Deletion of DDB1 in Mouse Brain and Lens Leads to P53-Dependent Elimination of Proliferating Cells. Cell 2006, 127, 929–940. [Google Scholar] [CrossRef] [PubMed]
- Liu, L.; Lee, S.; Zhang, J.; Peters, S.B.; Hannah, J.; Zhang, Y.; Yin, Y.; Koff, A.; Ma, L.; Zhou, P. CUL4A Abrogation Augments DNA Damage Response and Protection against Skin Carcinogenesis. Mol. Cell 2009, 34, 451–460. [Google Scholar] [CrossRef] [PubMed]
- Zhou, P.; Yan, F. CRL4 Ubiquitin Pathway and DNA Damage Response. Adv. Exp. Med. Biol. 2020, 1217, 225–239. [Google Scholar] [CrossRef] [PubMed]
- Kerzendorfer, C.; Hart, L.; Colnaghi, R.; Carpenter, G.; Alcantara, D.; Outwin, E.; Carr, A.M.; O’Driscoll, M. CUL4B-Deficiency in Humans: Understanding the Clinical Consequences of Impaired Cullin 4-RING E3 Ubiquitin Ligase Function. Mech. Ageing Dev. 2011, 132, 366–373. [Google Scholar] [CrossRef]
- Nakagawa, T.; Xiong, Y. X-Linked Mental Retardation Gene CUL4B Targets Ubiquitylation of H3K4 Methyltransferase Component WDR5 and Regulates Neuronal Gene Expression. Mol. Cell 2011, 43, 381–391. [Google Scholar] [CrossRef] [PubMed]
- Wen, X.; Duus, K.M.; Friedrich, T.D.; De Noronha, C.M.C. The HIV1 Protein Vpr Acts to Promote G2 Cell Cycle Arrest by Engaging a DDB1 and Cullin4A-Containing Ubiquitin Ligase Complex Using VprBP/DCAF1 as an Adaptor. J. Biol. Chem. 2007, 282, 27046–27051. [Google Scholar] [CrossRef]
- Iovine, B.; Iannella, M.L.; Bevilacqua, M.A. Damage-Specific DNA Binding Protein 1 (DDB1): A Protein with a Wide Range of Functions. Int. J. Biochem. Cell Biol. 2011, 43, 1664–1667. [Google Scholar] [CrossRef] [PubMed]
- Reichermeier, K.M.; Straube, R.; Reitsma, J.M.; Sweredoski, M.J.; Rose, C.M.; Moradian, A.; den Besten, W.; Hinkle, T.; Verschueren, E.; Petzold, G.; et al. PIKES Analysis Reveals Response to Degraders and Key Regulatory Mechanisms of the CRL4 Network. Mol. Cell 2020, 77, 1092–1106.e9. [Google Scholar] [CrossRef]
- Schabla, N.M.; Perry, G.A.; Palmer, V.L.; Swanson, P.C. VprBP (DCAF1) Regulates RAG1 Expression Independently of Dicer by Mediating RAG1 Degradation. J. Immunol. 2018, 201, 930–939. [Google Scholar] [CrossRef]
- Yu, C.; Zhang, Y.-L.; Pan, W.-W.; Li, X.-M.; Wang, Z.-W.; Ge, Z.-J.; Zhou, J.-J.; Cang, Y.; Tong, C.; Sun, Q.-Y.; et al. CRL4 Complex Regulates Mammalian Oocyte Survival and Reprogramming by Activation of TET Proteins. Science 2013, 342, 1518–1521. [Google Scholar] [CrossRef] [PubMed]
- Yoshizawa, T.; Karim, M.F.; Sato, Y.; Senokuchi, T.; Miyata, K.; Fukuda, T.; Go, C.; Tasaki, M.; Uchimura, K.; Kadomatsu, T.; et al. SIRT7 Controls Hepatic Lipid Metabolism by Regulating the Ubiquitin-Proteasome Pathway. Cell Metab. 2014, 19, 712–721. [Google Scholar] [CrossRef] [PubMed]
- Ren, W.; Shen, S.; Sun, Z.; Shu, P.; Shen, X.; Bu, C.; Ai, F.; Zhang, X.; Tang, A.; Tian, L.; et al. Jak-STAT3 Pathway Triggers DICER1 for Proteasomal Degradation by Ubiquitin Ligase Complex of CUL4A(DCAF1) to Promote Colon Cancer Development. Cancer Lett. 2016, 375, 209–220. [Google Scholar] [CrossRef]
- Kim, K.; Heo, K.; Choi, J.; Jackson, S.; Kim, H.; Xiong, Y.; An, W. Vpr-Binding Protein Antagonizes P53-Mediated Transcription via Direct Interaction with H3 Tail. Mol. Cell. Biol. 2012, 32, 783–796. [Google Scholar] [CrossRef]
- Guo, Z.; Kong, Q.; Liu, C.; Zhang, S.; Zou, L.; Yan, F.; Whitmire, J.K.; Xiong, Y.; Chen, X.; Wan, Y.Y. DCAF1 Controls T-Cell Function via P53-Dependent and -Independent Mechanisms. Nat. Commun. 2016, 7, 10307. [Google Scholar] [CrossRef] [PubMed]
- Kim, K.; Kim, J.-M.; Kim, J.-S.; Choi, J.; Lee, Y.S.; Neamati, N.; Song, J.S.; Heo, K.; An, W. VprBP Has Intrinsic Kinase Activity Targeting Histone H2A and Represses Gene Transcription. Mol. Cell 2013, 52, 459–467. [Google Scholar] [CrossRef]
- Hossain, D.; Javadi Esfehani, Y.; Das, A.; Tsang, W.Y. Cep78 Controls Centrosome Homeostasis by Inhibiting EDD-DYRK2-DDB1(Vpr)(BP). EMBO Rep. 2017, 18, 632–644. [Google Scholar] [CrossRef]
- Wu, Y.; Zhou, X.; Barnes, C.O.; DeLucia, M.; Cohen, A.E.; Gronenborn, A.M.; Ahn, J.; Calero, G. The DDB1-DCAF1-Vpr-UNG2 Crystal Structure Reveals How HIV-1 Vpr Steers Human UNG2 toward Destruction. Nat. Struct. Mol. Biol. 2016, 23, 933–940. [Google Scholar] [CrossRef]
- Wei, W.; Guo, H.; Han, X.; Liu, X.; Zhou, X.; Zhang, W.; Yu, X.F. A Novel DCAF1-Binding Motif Required for Vpx-Mediated Degradation of Nuclear SAMHD1 and Vpr-Induced G2 Arrest. Cell. Microbiol. 2012, 14, 1745–1756. [Google Scholar] [CrossRef]
- Wang, H.; Guo, H.; Su, J.; Rui, Y.; Zheng, W.; Gao, W.; Zhang, W.; Li, Z.; Liu, G.; Markham, R.B.; et al. Inhibition of Vpx-Mediated SAMHD1 and Vpr-Mediated Host Helicase Transcription Factor Degradation by Selective Disruption of Viral CRL4 (DCAF1) E3 Ubiquitin Ligase Assembly. J. Virol. 2017, 91, e00225-17. [Google Scholar] [CrossRef] [PubMed]
- Jacquot, G.; Le Rouzic, E.; Maidou-Peindara, P.; Maizy, M.; Lefrère, J.-J.; Daneluzzi, V.; Monteiro-Filho, C.M.R.; Hong, D.; Planelles, V.; Morand-Joubert, L.; et al. Characterization of the Molecular Determinants of Primary HIV-1 Vpr Proteins: Impact of the Q65R and R77Q Substitutions on Vpr Functions. PLoS ONE 2009, 4, e7514. [Google Scholar] [CrossRef] [PubMed]
- Hakata, Y.; Miyazawa, M.; Landau, N.R. Interactions with DCAF1 and DDB1 in the CRL4 E3 Ubiquitin Ligase Are Required for Vpr-Mediated G2 Arrest. Virol. J. 2014, 11, 108. [Google Scholar] [CrossRef]
- Maudet, C.; Bertrand, M.; Le Rouzic, E.; Lahouassa, H.; Ayinde, D.; Nisole, S.; Goujon, C.; Cimarelli, A.; Margottin-Goguet, F.; Transy, C. Molecular Insight into How HIV-1 Vpr Protein Impairs Cell Growth through Two Genetically Distinct Pathways. J. Biol. Chem. 2011, 286, 23742–23752. [Google Scholar] [CrossRef] [PubMed]
- DeHart, J.L.; Zimmerman, E.S.; Ardon, O.; Monteiro-Filho, C.M.R.; Argañaraz, E.R.; Planelles, V. HIV-1 Vpr Activates the G2 Checkpoint through Manipulation of the Ubiquitin Proteasome System. Virol. J. 2007, 4, 57. [Google Scholar] [CrossRef]
- Jacquot, G.; Le Rouzic, E.; David, A.; Mazzolini, J.; Bouchet, J.; Bouaziz, S.; Niedergang, F.; Pancino, G.; Benichou, S. Localization of HIV-1 Vpr to the Nuclear Envelope: Impact on Vpr Functions and Virus Replication in Macrophages. Retrovirology 2007, 4, 84. [Google Scholar] [CrossRef]
- Selig, L.; Benichou, S.; Rogel, M.E.; Wu, L.I.; Vodicka, M.A.; Sire, J.; Benarous, R.; Emerman, M. Uracil DNA Glycosylase Specifically Interacts with Vpr of Both Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus of Sooty Mangabeys, but Binding Does Not Correlate with Cell Cycle Arrest. J. Virol. 1997, 71, 4842–4846. [Google Scholar] [CrossRef] [PubMed]
- Schröfelbauer, B.; Yu, Q.; Zeitlin, S.G.; Landau, N.R. Human Immunodeficiency Virus Type 1 Vpr Induces the Degradation of the UNG and SMUG Uracil-DNA Glycosylases. J. Virol. 2005, 79, 10978–10987. [Google Scholar] [CrossRef]
- Zhou, X.; DeLucia, M.; Hao, C.; Hrecka, K.; Monnie, C.; Skowronski, J.; Ahn, J. HIV-1 Vpr Protein Directly Loads Helicase-like Transcription Factor (HLTF) onto the CRL4-DCAF1 E3 Ubiquitin Ligase. J. Biol. Chem. 2017, 292, 21117–21127. [Google Scholar] [CrossRef]
- Jowett, J.B.; Planelles, V.; Poon, B.; Shah, N.P.; Chen, M.L.; Chen, I.S. The Human Immunodeficiency Virus Type 1 Vpr Gene Arrests Infected T Cells in the G2 + M Phase of the Cell Cycle. J. Virol. 1995, 69, 6304–6313. [Google Scholar] [CrossRef]
- Rogel, M.E.; Wu, L.I.; Emerman, M. The Human Immunodeficiency Virus Type 1 Vpr Gene Prevents Cell Proliferation during Chronic Infection. J. Virol. 1995, 69, 882–888. [Google Scholar] [CrossRef] [PubMed]
- He, J.; Choe, S.; Walker, R.; Di Marzio, P.; Morgan, D.O.; Landau, N.R. Human Immunodeficiency Virus Type 1 Viral Protein R (Vpr) Arrests Cells in the G2 Phase of the Cell Cycle by Inhibiting P34cdc2 Activity. J. Virol. 1995, 69, 6705–6711. [Google Scholar] [CrossRef] [PubMed]
- Re, F.; Braaten, D.; Franke, E.K.; Luban, J. Human Immunodeficiency Virus Type 1 Vpr Arrests the Cell Cycle in G2 by Inhibiting the Activation of P34cdc2-Cyclin B. J. Virol. 1995, 69, 6859–6864. [Google Scholar] [CrossRef]
- Li, G.; Park, H.U.; Liang, D.; Zhao, R.Y. Cell Cycle G2/M Arrest through an S Phase-Dependent Mechanism by HIV-1 Viral Protein R. Retrovirology 2010, 7, 59. [Google Scholar] [CrossRef]
- de Silva, S.; Planelles, V.; Wu, L. Differential Effects of Vpr on Single-Cycle and Spreading HIV-1 Infections in CD4+ T-Cells and Dendritic Cells. PLoS ONE 2012, 7, e35385. [Google Scholar] [CrossRef]
- Goh, W.C.; Rogel, M.E.; Kinsey, C.M.; Michael, S.F.; Fultz, P.N.; Nowak, M.A.; Hahn, B.H.; Emerman, M. HIV-1 Vpr Increases Viral Expression by Manipulation of the Cell Cycle: A Mechanism for Selection of Vpr in Vivo. Nat. Med. 1998, 4, 65–71. [Google Scholar] [CrossRef] [PubMed]
- Tan, L.; Ehrlich, E.; Yu, X.-F. DDB1 and Cul4A Are Required for Human Immunodeficiency Virus Type 1 Vpr-Induced G 2 Arrest. J. Virol. 2007, 81, 10822–10830. [Google Scholar] [CrossRef]
- Le Rouzic, E.; Belaïdouni, N.; Estrabaud, E.; Morel, M.; Rain, J.C.; Transy, C.; Margottin-Goguet, F. HIV1 Vpr Arrests the Cell Cycle by Recruiting DCAF1/VprBP, a Receptor of the Cul4-DDB1 Ubiquitin Ligase. Cell Cycle 2007, 6, 182–188. [Google Scholar] [CrossRef]
- Schröfelbauer, B.; Hakata, Y.; Landau, N.R. HIV-1 Vpr Function Is Mediated by Interaction with the Damage-Specific DNA-Binding Protein DDB1. Proc. Natl. Acad. Sci. USA 2007, 104, 4130–4135. [Google Scholar] [CrossRef] [PubMed]
- Hrecka, K.; Gierszewska, M.; Srivastava, S.; Kozaczkiewicz, L.; Swanson, S.K.; Florens, L.; Washburn, M.P.; Skowronski, J. Lentiviral Vpr Usurps Cul4-DDB1[VprBP] E3 Ubiquitin Ligase to Modulate Cell Cycle. Proc. Natl. Acad. Sci. USA 2007, 104, 11778–11783. [Google Scholar] [CrossRef]
- Belzile, J.-P.; Duisit, G.; Rougeau, N.; Mercier, J.; Finzi, A.; Cohen, E.A. HIV-1 Vpr-Mediated G2 Arrest Involves the DDB1-CUL4AVPRBP E3 Ubiquitin Ligase. PLoS Pathog. 2007, 3, e85. [Google Scholar] [CrossRef] [PubMed]
- Belzile, J.-P.; Richard, J.; Rougeau, N.; Xiao, Y.; Cohen, E.A. HIV-1 Vpr Induces the K48-Linked Polyubiquitination and Proteasomal Degradation of Target Cellular Proteins to Activate ATR and Promote G2 Arrest. J. Virol. 2010, 84, 3320–3330. [Google Scholar] [CrossRef]
- Payliss, B.J.; Patel, A.; Sheppard, A.C.; Wyatt, H.D.M. Exploring the Structures and Functions of Macromolecular SLX4-Nuclease Complexes in Genome Stability. Front. Genet. 2021, 12, 784167. [Google Scholar] [CrossRef] [PubMed]
- Minocherhomji, S.; Hickson, I.D. Structure-Specific Endonucleases: Guardians of Fragile Site Stability. Trends Cell Biol. 2014, 24, 321–327. [Google Scholar] [CrossRef] [PubMed]
- Gallo-Fernández, M.; Saugar, I.; Ortiz-Bazán, M.Á.; Vázquez, M.V.; Tercero, J.A. Cell Cycle-Dependent Regulation of the Nuclease Activity of Mus81-Eme1/Mms4. Nucleic Acids Res. 2012, 40, 8325–8335. [Google Scholar] [CrossRef] [PubMed]
- Matos, J.; Blanco, M.G.; Maslen, S.; Skehel, J.M.; West, S.C. Regulatory Control of the Resolution of DNA Recombination Intermediates during Meiosis and Mitosis. Cell 2011, 147, 158–172. [Google Scholar] [CrossRef] [PubMed]
- Laguette, N.; Brégnard, C.; Hue, P.; Basbous, J.; Yatim, A.; Larroque, M.; Kirchhoff, F.; Constantinou, A.; Sobhian, B.; Benkirane, M. Premature Activation of the SLX4 Complex by Vpr Promotes G2/M Arrest and Escape from Innate Immune Sensing. Cell 2014, 156, 134–145. [Google Scholar] [CrossRef]
- Matsuoka, S.; Ballif, B.A.; Smogorzewska, A.; McDonald, E.R., 3rd; Hurov, K.E.; Luo, J.; Bakalarski, C.E.; Zhao, Z.; Solimini, N.; Lerenthal, Y.; et al. ATM and ATR Substrate Analysis Reveals Extensive Protein Networks Responsive to DNA Damage. Science 2007, 316, 1160–1166. [Google Scholar] [CrossRef]
- Mu, J.-J.; Wang, Y.; Luo, H.; Leng, M.; Zhang, J.; Yang, T.; Besusso, D.; Jung, S.Y.; Qin, J. A Proteomic Analysis of Ataxia Telangiectasia-Mutated (ATM)/ATM-Rad3-Related (ATR) Substrates Identifies the Ubiquitin-Proteasome System as a Regulator for DNA Damage Checkpoints. J. Biol. Chem. 2007, 282, 17330–17334. [Google Scholar] [CrossRef]
- Hamid, F.B.; Kim, J.; Shin, C.G. Distribution and Fate of HIV-1 Unintegrated DNA Species: A Comprehensive Update. AIDS Res. Ther. 2017, 14, 9. [Google Scholar] [CrossRef]
- Berger, G.; Lawrence, M.; Hué, S.; Neil, S.J.D. G2/M Cell Cycle Arrest Correlates with Primate Lentiviral Vpr Interaction with the SLX4 Complex. J. Virol. 2015, 89, 230–240. [Google Scholar] [CrossRef] [PubMed]
- Fregoso, O.I.; Emerman, M. Activation of the DNA Damage Response Is a Conserved Function of HIV-1 and HIV-2 Vpr That Is Independent of SLX4 Recruitment. mBio 2016, 7, e01433-16. [Google Scholar] [CrossRef] [PubMed]
- Zhou, X.; DeLucia, M.; Ahn, J. SLX4-SLX1 Protein-Independent Down-Regulation of MUS81-EME1 Protein by HIV-1 Viral Protein R (Vpr). J. Biol. Chem. 2016, 291, 16936–16947. [Google Scholar] [CrossRef]
- Cohen, É.A. From Arrest to Escape: HIV-1 Vpr Cuts a Deal. Cell Host Microbe 2014, 15, 125–127. [Google Scholar] [CrossRef]
- Brégnard, C.; Benkirane, M.; Laguette, N. DNA Damage Repair Machinery and HIV Escape from Innate Immune Sensing. Front. Microbiol. 2014, 5, 176. [Google Scholar] [CrossRef]
- Blondot, M.L.; Dragin, L.; Lahouassa, H.; Margottin-Goguet, F. How SLX4 Cuts through the Mystery of HIV-1 Vpr-Mediated Cell Cycle Arrest. Retrovirology 2014, 11, 1–9. [Google Scholar] [CrossRef] [PubMed]
- Rice, A.P.; Kimata, J.T. Subversion of Cell Cycle Regulatory Mechanisms by HIV. Cell Host Microbe 2015, 17, 736–740. [Google Scholar] [CrossRef]
- Baxley, R.M.; Bielinsky, A.-K. Mcm10: A Dynamic Scaffold at Eukaryotic Replication Forks. Genes 2017, 8, 73. [Google Scholar] [CrossRef] [PubMed]
- Romani, B.; Shaykh Baygloo, N.; Aghasadeghi, M.R.; Allahbakhshi, E. HIV-1 Vpr Protein Enhances Proteasomal Degradation of MCM10 DNA Replication Factor through the Cul4-DDB1[VprBP] E3 Ubiquitin Ligase to Induce G2/M Cell Cycle Arrest. J. Biol. Chem. 2015, 290, 17380–17389. [Google Scholar] [CrossRef]
- Chang, H.; Siarot, L.; Matsuura, R.; Lo, C.W.; Sato, H.; Otsuki, H.; Aida, Y. Distinct MCM10 Proteasomal Degradation Profiles by Primate Lentiviruses Vpr Proteins. Viruses 2020, 12, 98. [Google Scholar] [CrossRef]
- Greenwood, E.J.D.; Williamson, J.C.; Sienkiewicz, A.; Naamati, A.; Matheson, N.J.; Lehner, P.J. Promiscuous Targeting of Cellular Proteins by Vpr Drives Systems-Level Proteomic Remodeling in HIV-1 Infection. Cell Rep. 2019, 27, 1579–1596.e7. [Google Scholar] [CrossRef] [PubMed]
- Roux, K.J.; Kim, D.I.; Raida, M.; Burke, B. A Promiscuous Biotin Ligase Fusion Protein Identifies Proximal and Interacting Proteins in Mammalian Cells. J. Cell Biol. 2012, 196, 801–810. [Google Scholar] [CrossRef]
- Zhang, F.; Bieniasz, P.D. HIV-1 Vpr Induces Cell Cycle Arrest and Enhances Viral Gene Expression by Depleting CCDC137. eLife 2020, 9, e55806. [Google Scholar] [CrossRef] [PubMed]
- Youn, H.; Lee, H.-K.; Sohn, H.-R.; Park, U.-H.; Kim, E.-J.; Youn, B.; Um, S.-J. RaRF Confers RA Resistance by Sequestering RAR to the Nucleolus and Regulating MCL1 in Leukemia Cells. Oncogene 2018, 37, 352–362. [Google Scholar] [CrossRef] [PubMed]
- Zhao, L.J.; Wang, L.; Mukherjee, S.; Narayan, O. Biochemical Mechanism of HIV-1 Vpr Function. Oligomerization Mediated by the N-Terminal Domain. J. Biol. Chem. 1994, 269, 32131–32137. [Google Scholar] [CrossRef] [PubMed]
- Yao, X.J.; Subbramanian, R.A.; Rougeau, N.; Boisvert, F.; Bergeron, D.; Cohen, E.A. Mutagenic Analysis of Human Immunodeficiency Virus Type 1 Vpr: Role of a Predicted N-Terminal Alpha-Helical Structure in Vpr Nuclear Localization and Virion Incorporation. J. Virol. 1995, 69, 7032–7044. [Google Scholar] [CrossRef] [PubMed]
- Jenkins, Y.; McEntee, M.; Weis, K.; Greene, W.C. Characterization of HIV-1 Vpr Nuclear Import: Analysis of Signals and Pathways. J. Cell Biol. 1998, 143, 875–885. [Google Scholar] [CrossRef] [PubMed]
- Roshal, M.; Kim, B.; Zhu, Y.; Nghiem, P.; Planelles, V. Activation of the ATR-Mediated DNA Damage Response by the HIV-1 Viral Protein R. J. Biol. Chem. 2003, 278, 25879–25886. [Google Scholar] [CrossRef]
- Iijima, K.; Kobayashi, J.; Ishizaka, Y. Structural Alteration of DNA Induced by Viral Protein R of HIV-1 Triggers the DNA Damage Response. Retrovirology 2018, 15, 8. [Google Scholar] [CrossRef]
- Bouhamdan, M.; Benichou, S.; Rey, F.; Navarro, J.M.; Agostini, I.; Spire, B.; Camonis, J.; Slupphaug, G.; Vigne, R.; Benarous, R.; et al. Human Immunodeficiency Virus Type 1 Vpr Protein Binds to the Uracil DNA Glycosylase DNA Repair Enzyme. J. Virol. 1996, 70, 697–704. [Google Scholar] [CrossRef]
- Ahn, J.; Vu, T.; Novince, Z.; Guerrero-Santoro, J.; Rapic-Otrin, V.; Gronenborn, A.M. HIV-1 Vpr Loads Uracil DNA Glycosylase-2 onto DCAF1, a Substrate Recognition Subunit of a Cullin 4A-Ring E3 Ubiquitin Ligase for Proteasome-Dependent Degradation. J. Biol. Chem. 2010, 285, 37333–37341. [Google Scholar] [CrossRef]
- Kara, H.; Chazal, N.; Bouaziz, S. Is Uracil-DNA Glycosylase UNG2 a New Cellular Weapon Against HIV-1? Curr. HIV Res. 2019, 17, 148–160. [Google Scholar] [CrossRef] [PubMed]
- Priet, S.; Navarro, J.-M.; Gros, N.; Querat, G.; Sire, J. Functional Role of HIV-1 Virion-Associated Uracil DNA Glycosylase 2 in the Correction of G:U Mispairs to G:C Pairs. J. Biol. Chem. 2003, 278, 4566–4571. [Google Scholar] [CrossRef]
- Priet, S.; Gros, N.; Navarro, J.-M.; Boretto, J.; Canard, B.; Quérat, G.; Sire, J. HIV-1-Associated Uracil DNA Glycosylase Activity Controls DUTP Misincorporation in Viral DNA and Is Essential to the HIV-1 Life Cycle. Mol. Cell 2005, 17, 479–490. [Google Scholar] [CrossRef] [PubMed]
- Mansky, L.M.; Preveral, S.; Selig, L.; Benarous, R.; Benichou, S. The Interaction of Vpr with Uracil DNA Glycosylase Modulates the Human Immunodeficiency Virus Type 1 In Vivo Mutation Rate. J. Virol. 2000, 74, 7039–7047. [Google Scholar] [CrossRef] [PubMed]
- Klarmann, G.J.; Chen, X.; North, T.W.; Preston, B.D. Incorporation of Uracil into Minus Strand DNA Affects the Specificity of plus Strand Synthesis Initiation during Lentiviral Reverse Transcription. J. Biol. Chem. 2003, 278, 7902–7909. [Google Scholar] [CrossRef] [PubMed]
- Yang, B.; Chen, K.; Zhang, C.; Huang, S.; Zhang, H. Virion-Associated Uracil DNA Glycosylase-2 and Apurinic/Apyrimidinic Endonuclease Are Involved in the Degradation of APOBEC3G-Edited Nascent HIV-1 DNA. J. Biol. Chem. 2007, 282, 11667–11675. [Google Scholar] [CrossRef]
- Yan, N.; O’Day, E.; Wheeler, L.A.; Engelman, A.; Lieberman, J. HIV DNA Is Heavily Uracilated, Which Protects It from Autointegration. Proc. Natl. Acad. Sci. USA 2011, 108, 9244–9249. [Google Scholar] [CrossRef]
- Langevin, C.; Maidou-Peindara, P.; Aas, P.A.; Jacquot, G.; Otterlei, M.; Slupphaug, G.; Benichou, S. Human Immunodeficiency Virus Type 1 Vpr Modulates Cellular Expression of UNG2 via a Negative Transcriptional Effect. J. Virol. 2009, 83, 10256–10263. [Google Scholar] [CrossRef]
- Kaiser, S.M.; Emerman, M. Uracil DNA Glycosylase Is Dispensable for Human Immunodeficiency Virus Type 1 Replication and Does Not Contribute to the Antiviral Effects of the Cytidine Deaminase Apobec3G. J. Virol. 2006, 80, 875–882. [Google Scholar] [CrossRef] [PubMed]
- Hrecka, K.; Hao, C.; Shun, M.-C.; Kaur, S.; Swanson, S.K.; Florens, L.; Washburn, M.P.; Skowronski, J. HIV-1 and HIV-2 Exhibit Divergent Interactions with HLTF and UNG2 DNA Repair Proteins. Proc. Natl. Acad. Sci. USA 2016, 113, E3921–E3930. [Google Scholar] [CrossRef] [PubMed]
- Wen, X.; Klockow, L.; Nekorchuk, M.; Sharifi, H.J.; de Noronha, C.M.C. The HIV1 Protein Vpr Acts to Enhance Constitutive DCAF1-Dependent UNG2 Turnover. PLoS ONE 2012, 7, e30939. [Google Scholar] [CrossRef] [PubMed]
- Elserafy, M.; Abugable, A.A.; Atteya, R.; El-Khamisy, S.F. Rad5, HLTF, and SHPRH: A Fresh View of an Old Story. Trends Genet. 2018, 34, 574–577. [Google Scholar] [CrossRef] [PubMed]
- Lahouassa, H.; Blondot, M.-L.; Chauveau, L.; Chougui, G.; Morel, M.; Leduc, M.; Guillonneau, F.; Ramirez, B.C.; Schwartz, O.; Margottin-Goguet, F. HIV-1 Vpr Degrades the HLTF DNA Translocase in T Cells and Macrophages. Proc. Natl. Acad. Sci. USA 2016, 113, 5311–5316. [Google Scholar] [CrossRef] [PubMed]
- Manocheewa, S.; Lanxon-Cookson, E.C.; Liu, Y.; Swain, J.V.; McClure, J.; Rao, U.; Maust, B.; Deng, W.; Sunshine, J.E.; Kim, M.; et al. Pairwise Growth Competition Assay for Determining the Replication Fitness of Human Immunodeficiency Viruses. JoVE 2015, 99, e52610. [Google Scholar] [CrossRef]
- Yan, J.; Shun, M.C.; Zhang, Y.; Hao, C.; Skowronski, J. HIV-1 Vpr Counteracts HLTF-Mediated Restriction of HIV-1 Infection in T Cells. Proc. Natl. Acad. Sci. USA 2019, 116, 9568–9577. [Google Scholar] [CrossRef]
- Keijzers, G.; Liu, D.; Rasmussen, L.J. Exonuclease 1 and Its Versatile Roles in DNA Repair. Crit. Rev. Biochem. Mol. Biol. 2016, 51, 440–451. [Google Scholar] [CrossRef]
- Yan, J.; Shun, M.-C.; Hao, C.; Zhang, Y.; Qian, J.; Hrecka, K.; Delucia, M.; Monnie, C.; Ahn, J.; Skowronski, J. HIV-1 Vpr Reprograms CLR4 DCAF1 E3 Ubiquitin Ligase to Antagonize Exonuclease 1-Mediated Restriction of HIV-1 Infection. mBio 2018, 9, e01732-18. [Google Scholar] [CrossRef]
- Shen, R.; Richter, H.E.; Smith, P.D. Early HIV-1 Target Cells in Human Vaginal and Ectocervical Mucosa. Am. J. Reprod. Immunol. 2011, 65, 261–267. [Google Scholar] [CrossRef]
- Banga, R.; Perreau, M. The Multifaceted Nature of HIV Tissue Reservoirs. Curr. Opin. HIV AIDS 2024, 19, 116–123. [Google Scholar] [CrossRef] [PubMed]
- Calado, M.; Pires, D.; Conceição, C.; Santos-Costa, Q.; Anes, E.; Azevedo-Pereira, J.M. Human Immunodeficiency Virus Transmission-Mechanisms Underlying the Cell-to-Cell Spread of Human Immunodeficiency Virus. Rev. Med. Virol. 2023, 33, e2480. [Google Scholar] [CrossRef] [PubMed]
- Balliet, J.W.; Kolson, D.L.; Eiger, G.; Kim, F.M.; McGann, K.A.; Srinivasan, A.; Collman, R. Distinct Effects in Primary Macrophages and Lymphocytes of the Human Immunodeficiency Virus Type 1 Accessory Genes Vpr, Vpu, and Nef: Mutational Analysis of a Primary HIV-1 Isolate. Virology 1994, 200, 623–631. [Google Scholar] [CrossRef]
- Connor, R.I.; Chen, B.K.; Choe, S.; Landau, N.R. Vpr Is Required for Efficient Replication of Human Immunodeficiency Virus Type-1 in Mononuclear Phagocytes. Virology 1995, 206, 935–944. [Google Scholar] [CrossRef]
- Heinzinger, N.K.; Bukrinsky, M.I.; Haggerty, S.A.; Ragland, A.M.; Kewalramani, V.; Lee, M.A.; Gendelman, H.E.; Ratner, L.; Stevenson, M.; Emerman, M. The Vpr Protein of Human Immunodeficiency Virus Type 1 Influences Nuclear Localization of Viral Nucleic Acids in Nondividing Host Cells. Proc. Natl. Acad. Sci. USA 1994, 91, 7311–7315. [Google Scholar] [CrossRef] [PubMed]
- Subbramanian, R.A.; Kessous-Elbaz, A.; Lodge, R.; Forget, J.; Yao, X.J.; Bergeron, D.; Cohen, E.A. Human Immunodeficiency Virus Type 1 Vpr Is a Positive Regulator of Viral Transcription and Infectivity in Primary Human Macrophages. J. Exp. Med. 1998, 187, 1103–1111. [Google Scholar] [CrossRef]
- Vodicka, M.A.; Koepp, D.M.; Silver, P.A.; Emerman, M. HIV-1 Vpr Interacts with the Nuclear Transport Pathway to Promote Macrophage Infection. Genes Dev 1998, 12, 175–185. [Google Scholar] [CrossRef] [PubMed]
- Arribas, L.; Menéndez-Arias, L.; Betancor, G. May I Help You with Your Coat? HIV-1 Capsid Uncoating and Reverse Transcription. Int. J. Mol. Sci. 2024, 25, 7167. [Google Scholar] [CrossRef]
- Gibbons, J.M.; Marno, K.M.; Pike, R.; Lee, W.J.; Jones, C.E.; Ogunkolade, B.W.; Pardieu, C.; Bryan, A.; Fu, R.M.; Warnes, G.; et al. HIV-1 Accessory Protein Vpr Interacts with REAF/RPRD2 To Mitigate Its Antiviral Activity. J. Virol. 2020, 94, e01591-19. [Google Scholar] [CrossRef] [PubMed]
- Jackson-Jones, K.A.; McKnight, Á.; Sloan, R.D. The Innate Immune Factor RPRD2/REAF and Its Role in the Lv2 Restriction of HIV. MBio 2023, 14, e0257221. [Google Scholar] [CrossRef]
- Casey Klockow, L.; Sharifi, H.J.; Wen, X.; Flagg, M.; Furuya, A.K.M.; Nekorchuk, M.; De Noronha, C.M.C. The HIV-1 Protein Vpr Targets the Endoribonuclease Dicer for Proteasomal Degradation to Boost Macrophage Infection. Virology 2013, 444, 191–202. [Google Scholar] [CrossRef] [PubMed]
- Morando, N.; Rosenzvit, M.C.; Pando, M.A.; Allmer, J. The Role of MicroRNAs in HIV Infection. Genes 2024, 15, 574. [Google Scholar] [CrossRef] [PubMed]
- Mashiba, M.; Collins, D.R.; Terry, V.H.; Collins, K.L. Vpr Overcomes Macrophage-Specific Restriction of HIV-1 Env Expression and Virion Production. Cell Host Microbe 2014, 16, 722–735. [Google Scholar] [CrossRef] [PubMed]
- Collins, D.R.; Lubow, J.; Lukic, Z.; Mashiba, M.; Collins, K.L. Vpr Promotes Macrophage-Dependent HIV-1 Infection of CD4+ T Lymphocytes. PLoS Pathog. 2015, 11, e1005054. [Google Scholar] [CrossRef] [PubMed]
- Wang, Q.; Su, L. Vpr Enhances HIV-1 Env Processing and Virion Infectivity in Macrophages by Modulating TET2-Dependent IFITM3 Expression. mBio 2019, 10, e01344-19. [Google Scholar] [CrossRef] [PubMed]
- Lubow, J.; Virgilio, M.C.; Merlino, M.; Collins, D.R.; Mashiba, M.; Peterson, B.G.; Lukic, Z.; Painter, M.M.; Gomez-Rivera, F.; Terry, V.; et al. Mannose Receptor Is an HIV Restriction Factor Counteracted by Vpr in Macrophages. eLife 2020, 9, e51035. [Google Scholar] [CrossRef] [PubMed]
- Turkistany, S.A.; DeKoter, R.P. The Transcription Factor PU.1 Is a Critical Regulator of Cellular Communication in the Immune System. Arch. Immunol. Ther. Exp. (Warsz.) 2011, 59, 431–440. [Google Scholar] [CrossRef] [PubMed]
- Fisher, R.C.; Scott, E.W. Role of PU.1 in Hematopoiesis. Stem Cells 1998, 16, 25–37. [Google Scholar] [CrossRef]
- Virgilio, M.C.; Ramnani, B.; Chen, T.; Disbennett, W.M.; Lubow, J.; Welch, J.D.; Collins, K.L. HIV-1 Vpr Combats the PU.1-Driven Antiviral Response in Primary Human Macrophages. Nat. Commun. 2024, 15, 5514. [Google Scholar] [CrossRef]
- Zhao, L.; Wang, S.; Xu, M.; He, Y.; Zhang, X.; Xiong, Y.; Sun, H.; Ding, H.; Geng, W.; Shang, H.; et al. Vpr Counteracts the Restriction of LAPTM5 to Promote HIV-1 Infection in Macrophages. Nat. Commun. 2021, 12, 3691. [Google Scholar] [CrossRef]
- Ouyang, J.; Xiong, Y.; Shang, H.; Liang, G. LAPTM5 Restricts HIV-1 Infection in Dendritic Cells and Is Counteracted by Vpr. Microbiol. Spectr. 2022, 10, e0138221. [Google Scholar] [CrossRef]
- Zhang, X.; Zhou, T.; Frabutt, D.A.; Zheng, Y.H. HIV-1 Vpr Increases Env Expression by Preventing Env from Endoplasmic Reticulum-Associated Protein Degradation (ERAD). Virology 2016, 496, 194–202. [Google Scholar] [CrossRef] [PubMed]
- Miller, C.M.; Akiyama, H.; Agosto, L.M.; Emery, A.; Ettinger, C.R.; Swanstrom, R.I.; Henderson, A.J.; Gummuluru, S. Virion-Associated Vpr Alleviates a Postintegration Block to HIV-1 Infection of Dendritic Cells. J. Virol. 2017, 91, e00051-17. [Google Scholar] [CrossRef] [PubMed]
- Kao, S.; Miyagi, E.; Mallorson, R.; Saito, H.; Sukegawa, S.; Mukherji, A.; Mateja, A.; Ferhadian, D.; Fabryova, H.; Clouse, K.; et al. The Myeloid-Specific Transcription Factor PU.1 Upregulates Mannose Receptor Expression but Represses Basal Activity of the HIV-LTR Promoter. J. Virol. 2022, 96, e0065222. [Google Scholar] [CrossRef] [PubMed]
- Maudet, C.; Sourisce, A.; Dragin, L.; Lahouassa, H.; Rain, J.C.; Bouaziz, S.; Ramirez, B.C.; Margottin-Goguet, F. HIV-1 Vpr Induces the Degradation of ZIP and SZIP, Adaptors of the NuRD Chromatin Remodeling Complex, by Hijacking DCAF1/VprBP. PLoS ONE 2013, 8, e77320. [Google Scholar] [CrossRef] [PubMed]
- Yu, W.; Li, R.; Gui, B.; Shang, Y. SZIP, an Alternative Splice Variant of ZIP, Antagonizes Transcription Repression and Growth Inhibition by ZIP. J. Biol. Chem. 2010, 285, 14301–14307. [Google Scholar] [CrossRef]
- Zhou, X.; Monnie, C.; DeLucia, M.; Ahn, J. HIV-1 Vpr Activates Host CRL4-DCAF1 E3 Ligase to Degrade Histone Deacetylase SIRT7. Virol. J. 2021, 18, 48. [Google Scholar] [CrossRef]
- Romani, B.; Baygloo, N.S.; Hamidi-Fard, M.; Aghasadeghi, M.R.; Allahbakhshi, E. HIV-1 Vpr Protein Induces Proteasomal Degradation of Chromatin-Associated Class I HDACs to Overcome Latent Infection of Macrophages. J. Biol. Chem. 2016, 291, 2696–2711. [Google Scholar] [CrossRef]
- Romani, B.; Kamali Jamil, R.; Hamidi-Fard, M.; Rahimi, P.; Momen, S.B.; Aghasadeghi, M.R.; Allahbakhshi, E. HIV-1 Vpr Reactivates Latent HIV-1 Provirus by Inducing Depletion of Class i HDACs on Chromatin. Sci. Rep. 2016, 6, 31924. [Google Scholar] [CrossRef]
- Cismasiu, V.B.; Adamo, K.; Gecewicz, J.; Duque, J.; Lin, Q.; Avram, D. BCL11B Functionally Associates with the NuRD Complex in T Lymphocytes to Repress Targeted Promoter. Oncogene 2005, 24, 6753–6764. [Google Scholar] [CrossRef] [PubMed]
- Marban, C.; Suzanne, S.; Dequiedt, F.; de Walque, S.; Redel, L.; Van Lint, C.; Aunis, D.; Rohr, O. Recruitment of Chromatin-Modifying Enzymes by CTIP2 Promotes HIV-1 Transcriptional Silencing. EMBO J. 2007, 26, 412–423. [Google Scholar] [CrossRef]
- Eilebrecht, S.; Le Douce, V.; Riclet, R.; Targat, B.; Hallay, H.; Van Driessche, B.; Schwartz, C.; Robette, G.; Van Lint, C.; Rohr, O.; et al. HMGA1 Recruits CTIP2-Repressed P-TEFb to the HIV-1 and Cellular Target Promoters. Nucleic Acids Res. 2014, 42, 4962–4971. [Google Scholar] [CrossRef]
- Forouzanfar, F.; Ali, S.; Wallet, C.; De Rovere, M.; Ducloy, C.; El Mekdad, H.; El Maassarani, M.; Aït-Ammar, A.; Van Assche, J.; Boutant, E.; et al. HIV-1 Vpr Mediates the Depletion of the Cellular Repressor CTIP2 to Counteract Viral Gene Silencing. Sci. Rep. 2019, 9, 13154. [Google Scholar] [CrossRef] [PubMed]
- Wang, G.Z.; Wang, Y.; Goff, S.P. Histones Are Rapidly Loaded onto Unintegrated Retroviral DNAs Soon after Nuclear Entry. Cell Host Microbe 2016, 20, 798–809. [Google Scholar] [CrossRef] [PubMed]
- Geis, F.K.; Goff, S.P. Unintegrated HIV-1 DNAs Are Loaded with Core and Linker Histones and Transcriptionally Silenced. Proc. Natl. Acad. Sci. USA 2019, 116, 23735–23742. [Google Scholar] [CrossRef] [PubMed]
- Dupont, L.; Bloor, S.; Williamson, J.C.; Cuesta, S.M.; Shah, R.; Teixeira-Silva, A.; Naamati, A.; Greenwood, E.J.D.; Sarafianos, S.G.; Matheson, N.J.; et al. The SMC5/6 Complex Compacts and Silences Unintegrated HIV-1 DNA and Is Antagonized by Vpr. Cell Host Microbe 2021, 29, 792–805.e6. [Google Scholar] [CrossRef] [PubMed]
- Nakagawa, T.; Lv, L.; Nakagawa, M.; Yu, Y.; Yu, C.; D’Alessio, A.C.; Nakayama, K.; Fan, H.-Y.; Chen, X.; Xiong, Y. CRL4VprBP E3 Ligase Promotes Monoubiquitylation and Chromatin Binding of TET Dioxygenases. Mol. Cell 2015, 57, 247–260. [Google Scholar] [CrossRef] [PubMed]
- Lv, L.; Wang, Q.; Xu, Y.; Tsao, L.C.; Nakagawa, T.; Guo, H.; Su, L.; Xiong, Y. Vpr Targets TET2 for Degradation by CRL4 VprBP E3 Ligase to Sustain IL-6 Expression and Enhance HIV-1 Replication. Mol. Cell 2018, 70, 961–970.e5. [Google Scholar] [CrossRef] [PubMed]
- Deeks, S.G.; Lewin, S.R.; Havlir, D. V The End of AIDS: HIV Infection as a Chronic Disease. Lancet 2013, 382, 1525–1533. [Google Scholar] [CrossRef] [PubMed]
- Khan, H.; Sumner, R.P.; Rasaiyaah, J.; Tan, C.P.; Rodriguez-Plata, M.T.; Van Tulleken, C.; Fink, D.; Zuliani-Alvarez, L.; Thorne, L.; Stirling, D.; et al. Hiv-1 Vpr Antagonizes Innate Immune Activation by Targeting Karyopherin-Mediated Nf-Κb/Irf3 Nuclear Transport. eLife 2020, 9, e60821. [Google Scholar] [CrossRef]
- Fouchier, R.A.; Meyer, B.E.; Simon, J.H.; Fischer, U.; Albright, A.V.; González-Scarano, F.; Malim, M.H. Interaction of the Human Immunodeficiency Virus Type 1 Vpr Protein with the Nuclear Pore Complex. J. Virol. 1998, 72, 6004–6013. [Google Scholar] [CrossRef]
- Okumura, A.; Alce, T.; Lubyova, B.; Ezelle, H.; Strebel, K.; Pitha, P.M. HIV-1 Accessory Proteins VPR and Vif Modulate Antiviral Response by Targeting IRF-3 for Degradation. Virology 2008, 373, 85–97. [Google Scholar] [CrossRef]
- Hotter, D.; Krabbe, T.; Reith, E.; Gawanbacht, A.; Rahm, N.; Ayouba, A.; Van Driessche, B.; Van Lint, C.; Peeters, M.; Kirchhoff, F.; et al. Primate Lentiviruses Use at Least Three Alternative Strategies to Suppress NF-ΚB-Mediated Immune Activation. PLoS Pathog. 2017, 13, e1006598. [Google Scholar] [CrossRef] [PubMed]
- Kumar, A.; Coquard, L.; Herbein, G. Targeting TNF-Alpha in HIV-1 Infection. Curr. Drug Targets 2016, 17, 15–22. [Google Scholar] [CrossRef] [PubMed]
- Liu, R.; Lin, Y.; Jia, R.; Geng, Y.; Liang, C.; Tan, J.; Qiao, W. HIV-1 Vpr Stimulates NF-ΚB and AP-1 Signaling by Activating TAK1. Retrovirology 2014, 11, 45. [Google Scholar] [CrossRef] [PubMed]
- Roesch, F.; Richard, L.; Rua, R.; Porrot, F.; Casartelli, N.; Schwartz, O. Vpr Enhances Tumor Necrosis Factor Production by HIV-1-Infected T Cells. J. Virol. 2015, 89, 12118–12130. [Google Scholar] [CrossRef] [PubMed]
- Zhou, D.; Wang, Y.; Tokunaga, K.; Huang, F.; Sun, B.; Yang, R. The HIV-1 Accessory Protein Vpr Induces the Degradation of the Anti-HIV-1 Agent APOBEC3G through a VprBP-Mediated Proteasomal Pathway. Virus Res. 2015, 195, 25–34. [Google Scholar] [CrossRef] [PubMed]
- Sawyer, S.L.; Emerman, M.; Malik, H.S. Ancient Adaptive Evolution of the Primate Antiviral DNA-Editing Enzyme APOBEC3G. PLoS Biol. 2004, 2, E275. [Google Scholar] [CrossRef]
- Salamango, D.J.; Harris, R.S. Demystifying Cell Cycle Arrest by HIV-1 Vif. Trends Microbiol. 2021, 29, 381–384. [Google Scholar] [CrossRef] [PubMed]
- Wong, H.T.; Luperchio, A.M.; Riley, S.; Salamango, D.J. Inhibition of ATM-Directed Antiviral Responses by HIV-1 Vif. PLoS Pathog. 2023, 19, e1011634. [Google Scholar] [CrossRef]
- Muthumani, K.; Choo, A.Y.; Premkumar, A.; Hwang, D.S.; Thieu, K.P.; Desai, B.M.; Weiner, D.B. Human Immunodeficiency Virus Type 1 (HIV-1) Vpr-Regulated Cell Death: Insights into Mechanism. Cell Death Differ. 2005, 12, 962–970. [Google Scholar] [CrossRef]
- Chang, L.J.; Chen, C.H.; Urlacher, V.; Lee, T.Z. Differential Apoptosis Effects of Primate Lentiviral Vpr and Vpx in Mammalian Cells. J. Biomed. Sci. 2000, 7, 322–333. [Google Scholar] [CrossRef]
- Jacotot, E.; Ravagnan, L.; Loeffler, M.; Ferri, K.F.; Vieira, H.L.; Zamzami, N.; Costantini, P.; Druillennec, S.; Hoebeke, J.; Briand, J.P.; et al. The HIV-1 Viral Protein R Induces Apoptosis via a Direct Effect on the Mitochondrial Permeability Transition Pore. J. Exp. Med. 2000, 191, 33–46. [Google Scholar] [CrossRef]
- Huang, C.-Y.; Chiang, S.-F.; Lin, T.-Y.; Chiou, S.-H.; Chow, K.-C. HIV-1 Vpr Triggers Mitochondrial Destruction by Impairing Mfn2-Mediated ER-Mitochondria Interaction. PLoS ONE 2012, 7, e33657. [Google Scholar] [CrossRef]
- Ferrucci, A.; Nonnemacher, M.R.; Wigdahl, B. Human Immunodeficiency Virus Viral Protein R as an Extracellular Protein in Neuropathogenesis. Adv. Virus Res. 2011, 81, 165–199. [Google Scholar] [CrossRef]
- Mo, M.; Shahar, S.; Fleming, S.B.; Mercer, A.A. How Viruses Affect the Cell Cycle through Manipulation of the APC/C. Trends Microbiol. 2012, 20, 440–448. [Google Scholar] [CrossRef] [PubMed]
- Barbosa, J.A.F.; Sparapani, S.; Boulais, J.; Lodge, R.; Cohen, É.A. Human Immunodeficiency Virus Type 1 Vpr Mediates Degradation of APC1, a Scaffolding Component of the Anaphase-Promoting Complex/Cyclosome. J. Virol. 2021, 95, e00971-20. [Google Scholar] [CrossRef] [PubMed]
- Wang, X.; Singh, S.; Jung, H.Y.; Yang, G.; Jun, S.; Sastry, K.J.; Park, J. Il HIV-1 Vpr Protein Inhibits Telomerase Activity via the EDD-DDB1-VPRBP E3 Ligase Complex. J. Biol. Chem. 2013, 288, 15474–15480. [Google Scholar] [CrossRef] [PubMed]
- Deeks, S.G. HIV Infection, Inflammation, Immunosenescence, and Aging. Annu. Rev. Med. 2011, 62, 141–155. [Google Scholar] [CrossRef]
- Hossain, D.; Barbosa, J.A.F.; Cohen, E.A.; Tsang, W.Y. HIV-1 Vpr Hijacks EDD-DYRK2-DDB1DCAF1 to Disrupt Centrosome Homeostasis. J. Biol. Chem. 2018, 293, 9448–9460. [Google Scholar] [CrossRef]
- Stephens, C.; Naghavi, M.H. The Host Cytoskeleton: A Key Regulator of Early HIV-1 Infection. FEBS J. 2024, 291, 1835–1848. [Google Scholar] [CrossRef]
- Park, J.-E.; Kim, T.-S.; Zeng, Y.; Mikolaj, M.; Il Ahn, J.; Alam, M.S.; Monnie, C.M.; Shi, V.; Zhou, M.; Chun, T.-W.; et al. Centrosome Amplification and Aneuploidy Driven by the HIV-1-Induced Vpr•VprBP•Plk4 Complex in CD4(+) T Cells. Nat. Commun. 2024, 15, 2017. [Google Scholar] [CrossRef]
- Fletcher, T.M., 3rd; Brichacek, B.; Sharova, N.; Newman, M.A.; Stivahtis, G.; Sharp, P.M.; Emerman, M.; Hahn, B.H.; Stevenson, M. Nuclear Import and Cell Cycle Arrest Functions of the HIV-1 Vpr Protein Are Encoded by Two Separate Genes in HIV-2/SIV(SM). EMBO J. 1996, 15, 6155–6165. [Google Scholar] [CrossRef]
- Bergamaschi, A.; Ayinde, D.; David, A.; Le Rouzic, E.; Morel, M.; Collin, G.; Descamps, D.; Damond, F.; Brun-Vezinet, F.; Nisole, S.; et al. The Human Immunodeficiency Virus Type 2 Vpx Protein Usurps the CUL4A-DDB1 DCAF1 Ubiquitin Ligase to Overcome a Postentry Block in Macrophage Infection. J. Virol. 2009, 83, 4854–4860. [Google Scholar] [CrossRef] [PubMed]
- Sharova, N.; Wu, Y.; Zhu, X.; Stranska, R.; Kaushik, R.; Sharkey, M.; Stevenson, M. Primate Lentiviral Vpx Commandeers DDB1 to Counteract a Macrophage Restriction. PLoS Pathog. 2008, 4, e1000057. [Google Scholar] [CrossRef]
- Srivastava, S.; Swanson, S.K.; Manel, N.; Florens, L.; Washburn, M.P.; Skowronski, J. Lentiviral Vpx Accessory Factor Targets VprBP/DCAF1 Substrate Adaptor for Cullin 4 E3 Ubiquitin Ligase to Enable Macrophage Infection. PLoS Pathog. 2008, 4, e1000059. [Google Scholar] [CrossRef]
- Berger, A.; Münk, C.; Schweizer, M.; Cichutek, K.; Schüle, S.; Flory, E. Interaction of Vpx and Apolipoprotein B MRNA-Editing Catalytic Polypeptide 3 Family Member A (APOBEC3A) Correlates with Efficient Lentivirus Infection of Monocytes. J. Biol. Chem. 2010, 285, 12248–12254. [Google Scholar] [CrossRef] [PubMed]
- Romani, B.; Cohen, E.A. Lentivirus Vpr and Vpx Accessory Proteins Usurp the Cullin4-DDB1 (DCAF1) E3 Ubiquitin Ligase. Curr. Opin. Virol. 2012, 2, 755–763. [Google Scholar] [CrossRef]
- Laguette, N.; Sobhian, B.; Casartelli, N.; Ringeard, M.; Chable-Bessia, C.; Segeral, E.; Yatim, A.; Emiliani, S.; Schwartz, O.; Benkirane, M. SAMHD1 Is the Dendritic- and Myeloid-Cell-Specific HIV-1 Restriction Factor Counteracted by Vpx. Nature 2011, 474, 654–657. [Google Scholar] [CrossRef]
- Schwefel, D.; Groom, H.C.T.; Boucherit, V.C.; Christodoulou, E.; Walker, P.A.; Stoye, J.P.; Bishop, K.N.; Taylor, I.A. Structural Basis of Lentiviral Subversion of a Cellular Protein Degradation Pathway. Nature 2014, 505, 234–238. [Google Scholar] [CrossRef] [PubMed]
- Miyake, A.; Fujita, M.; Fujino, H.; Koga, R.; Kawamura, S.; Otsuka, M.; Ode, H.; Iwatani, Y.; Sakai, Y.; Doi, N.; et al. Poly-Proline Motif in HIV-2 Vpx Is Critical for Its Efficient Translation. J. Gen. Virol. 2014, 95, 179–189. [Google Scholar] [CrossRef] [PubMed]
- Ciftci, H.I.; Fujino, H.; Koga, R.; Yamamoto, M.; Kawamura, S.; Tateishi, H.; Iwatani, Y.; Otsuka, M.; Fujita, M. Mutational Analysis of HIV-2 Vpx Shows That Proline Residue 109 in the Poly-Proline Motif Regulates Degradation of SAMHD1. FEBS Lett. 2015, 589, 1505–1514. [Google Scholar] [CrossRef] [PubMed]
- Martin, M.M.; Matkovic, R.; Larrous, P.; Morel, M.; Lasserre, A.; Vauthier, V.; Margottin-Goguet, F. Binding to DCAF1 Distinguishes TASOR and SAMHD1 Degradation by HIV-2 Vpx. PLoS Pathog. 2021, 17, e1009609. [Google Scholar] [CrossRef]
- Hrecka, K.; Hao, C.; Gierszewska, M.; Swanson, S.K.; Kesik-Brodacka, M.; Srivastava, S.; Florens, L.; Washburn, M.P.; Skowronski, J. Vpx Relieves Inhibition of HIV-1 Infection of Macrophages Mediated by the SAMHD1 Protein. Nature 2011, 474, 658–661. [Google Scholar] [CrossRef]
- Cribier, A.; Descours, B.; Valadao, A.L.; Laguette, N.; Benkirane, M. Phosphorylation of SAMHD1 by Cyclin A2/CDK1 Regulates Its Restriction Activity toward HIV-1. Cell Rep. 2013, 3, 1036–1043. [Google Scholar] [CrossRef] [PubMed]
- Szaniawski, M.A.; Spivak, A.M.; Cox, J.E.; Catrow, J.L.; Hanley, T.; Williams, E.; Tremblay, M.J.; Bosque, A.; Planelles, V. SAMHD1 Phosphorylation Coordinates the Anti-HIV-1 Response by Diverse Interferons and Tyrosine Kinase Inhibition. mBio 2018, 9, e00819-18. [Google Scholar] [CrossRef]
- Ahn, J.; Hao, C.; Yan, J.; DeLucia, M.; Mehrens, J.; Wang, C.; Gronenborn, A.M.; Skowronski, J. HIV/Simian Immunodeficiency Virus (SIV) Accessory Virulence Factor Vpx Loads the Host Cell Restriction Factor SAMHD1 onto the E3 Ubiquitin Ligase Complex CRL4DCAF1. J. Biol. Chem. 2012, 287, 12550–12558. [Google Scholar] [CrossRef]
- Fregoso, O.I.; Ahn, J.; Wang, C.; Mehrens, J.; Skowronski, J.; Emerman, M. Evolutionary Toggling of Vpx/Vpr Specificity Results in Divergent Recognition of the Restriction Factor SAMHD1. PLoS Pathog. 2013, 9, e1003496. [Google Scholar] [CrossRef] [PubMed]
- Baldauf, H.-M.; Pan, X.; Erikson, E.; Schmidt, S.; Daddacha, W.; Burggraf, M.; Schenkova, K.; Ambiel, I.; Wabnitz, G.; Gramberg, T.; et al. SAMHD1 Restricts HIV-1 Infection in Resting CD4(+) T Cells. Nat. Med. 2012, 18, 1682–1687. [Google Scholar] [CrossRef]
- Lahouassa, H.; Daddacha, W.; Hofmann, H.; Ayinde, D.; Logue, E.C.; Dragin, L.; Bloch, N.; Maudet, C.; Bertrand, M.; Gramberg, T.; et al. SAMHD1 Restricts HIV-1 Infection in Dendritic Cells (DCs) by DNTP Depletion, but Its Expression in DCs and Primary CD4+ T-Lymphocytes Cannot Be Upregulated by Interferons. Nat. Immunol. 2012, 9, 223–228. [Google Scholar] [CrossRef]
- Diamond, T.L.; Roshal, M.; Jamburuthugoda, V.K.; Reynolds, H.M.; Merriam, A.R.; Lee, K.Y.; Balakrishnan, M.; Bambara, R.A.; Planelles, V.; Dewhurst, S.; et al. Macrophage Tropism of HIV-1 Depends on Efficient Cellular DNTP Utilization by Reverse Transcriptase. J. Biol. Chem. 2004, 279, 51545–51553. [Google Scholar] [CrossRef]
- Yan, J.; Hao, C.; DeLucia, M.; Swanson, S.; Florens, L.; Washburn, M.P.; Ahn, J.; Skowronski, J. CyclinA2-Cyclin-Dependent Kinase Regulates SAMHD1 Protein Phosphohydrolase Domain. J. Biol. Chem. 2015, 290, 13279–13292. [Google Scholar] [CrossRef] [PubMed]
- Mauney, C.H.; Rogers, L.C.; Harris, R.S.; Daniel, L.W.; Devarie-Baez, N.O.; Wu, H.; Furdui, C.M.; Poole, L.B.; Perrino, F.W.; Hollis, T. The SAMHD1 DNTP Triphosphohydrolase Is Controlled by a Redox Switch. Antioxid. Redox Signal. 2017, 27, 1317–1331. [Google Scholar] [CrossRef]
- Reinhard, C.; Bottinelli, D.; Kim, B.; Luban, J. Vpx Rescue of HIV-1 from the Antiviral State in Mature Dendritic Cells Is Independent of the Intracellular Deoxynucleotide Concentration. Retrovirology 2014, 11, 12. [Google Scholar] [CrossRef]
- Welbourn, S.; Strebel, K. Low DNTP Levels Are Necessary but May Not Be Sufficient for Lentiviral Restriction by SAMHD1. Virology 2016, 488, 271–277. [Google Scholar] [CrossRef] [PubMed]
- White, T.E.; Brandariz-Nunez, A.; Valle-Casuso, J.C.; Amie, S.; Nguyen, L.A.; Kim, B.; Tuzova, M.; Diaz-Griffero, F. The Retroviral Restriction Ability of SAMHD1, but Not Its Deoxynucleotide Triphosphohydrolase Activity, Is Regulated by Phosphorylation. Cell Host Microbe 2013, 13, 441–451. [Google Scholar] [CrossRef]
- Wang, Z.; Bhattacharya, A.; White, T.; Buffone, C.; McCabe, A.; Nguyen, L.A.; Shepard, C.N.; Pardo, S.; Kim, B.; Weintraub, S.T.; et al. Functionality of Redox-Active Cysteines Is Required for Restriction of Retroviral Replication by SAMHD1. Cell Rep. 2018, 24, 815–823. [Google Scholar] [CrossRef]
- Furuya, A.K.; Sharifi, H.J.; Jellinger, R.M.; Cristofano, P.; Shi, B.; de Noronha, C.M. Sulforaphane Inhibits HIV Infection of Macrophages through Nrf2. PLoS Pathog. 2016, 12, e1005581. [Google Scholar] [CrossRef] [PubMed]
- Sharifi, H.J.; Paine, D.N.; Fazzari, V.A.; Tipple, A.F.; Patterson, E.; de Noronha, C.M.C. Sulforaphane Reduces SAMHD1 Phosphorylation To Protect Macrophages from HIV-1 Infection. J. Virol. 2022, 96, e0118722. [Google Scholar] [CrossRef] [PubMed]
- Guo, H.; Yang, W.; Li, H.; Yang, J.; Huang, Y.; Tang, Y.; Wang, S.; Ni, F.; Yang, W.; Yu, X.-F.; et al. The SAMHD1-MX2 Axis Restricts HIV-1 Infection at Postviral DNA Synthesis. mBio 2024, 15, e0136324. [Google Scholar] [CrossRef]
- Coggins, S.A.; Mahboubi, B.; Schinazi, R.F.; Kim, B. SAMHD1 Functions and Human Diseases. Viruses 2020, 12, 382. [Google Scholar] [CrossRef]
- Guyader, M.; Emerman, M.; Montagnier, L.; Peden, K. VPX Mutants of HIV-2 Are Infectious in Established Cell Lines but Display a Severe Defect in Peripheral Blood Lymphocytes. EMBO J. 1989, 8, 1169–1175. [Google Scholar] [CrossRef] [PubMed]
- Baldauf, H.-M.; Stegmann, L.; Schwarz, S.-M.; Ambiel, I.; Trotard, M.; Martin, M.; Burggraf, M.; Lenzi, G.M.; Lejk, H.; Pan, X.; et al. Vpx Overcomes a SAMHD1-Independent Block to HIV Reverse Transcription That Is Specific to Resting CD4 T Cells. Proc. Natl. Acad. Sci. USA 2017, 114, 2729–2734. [Google Scholar] [CrossRef] [PubMed]
- Pertel, T.; Reinhard, C.; Luban, J. Vpx Rescues HIV-1 Transduction of Dendritic Cells from the Antiviral State Established by Type 1 Interferon. Retrovirology 2011, 8, 49. [Google Scholar] [CrossRef]
- Müller, I.; Helin, K. Keep Quiet: The HUSH Complex in Transcriptional Silencing and Disease. Nat. Struct. Mol. Biol. 2024, 31, 11–22. [Google Scholar] [CrossRef]
- Chougui, G.; Munir-Matloob, S.; Matkovic, R.; Martin, M.M.; Morel, M.; Lahouassa, H.; Leduc, M.; Ramirez, B.C.; Etienne, L.; Margottin-Goguet, F. HIV-2/SIV Viral Protein X Counteracts HUSH Repressor Complex. Nat. Microbiol. 2018, 3, 891–897. [Google Scholar] [CrossRef] [PubMed]
- Yurkovetskiy, L.; Guney, M.H.; Kim, K.; Goh, S.L.; McCauley, S.; Dauphin, A.; Diehl, W.E.; Luban, J. Primate Immunodeficiency Virus Proteins Vpx and Vpr Counteract Transcriptional Repression of Proviruses by the HUSH Complex. Nat. Microbiol. 2018, 3, 1354–1361. [Google Scholar] [CrossRef] [PubMed]
- Peng, G.; Greenwell-Wild, T.; Nares, S.; Jin, W.; Lei, K.J.; Rangel, Z.G.; Munson, P.J.; Wahl, S.M. Myeloid Differentiation and Susceptibility to HIV-1 Are Linked to APOBEC3 Expression. Blood 2007, 110, 393–400. [Google Scholar] [CrossRef]
- Berger, G.; Durand, S.; Fargier, G.; Nguyen, X.-N.; Cordeil, S.; Bouaziz, S.; Muriaux, D.; Darlix, J.-L.; Cimarelli, A. APOBEC3A Is a Specific Inhibitor of the Early Phases of HIV-1 Infection in Myeloid Cells. PLoS Pathog. 2011, 7, e1002221. [Google Scholar] [CrossRef] [PubMed]
- Taura, M.; Song, E.; Ho, Y.-C.; Iwasaki, A. Apobec3A Maintains HIV-1 Latency through Recruitment of Epigenetic Silencing Machinery to the Long Terminal Repeat. Proc. Natl. Acad. Sci. USA 2019, 116, 2282–2289. [Google Scholar] [CrossRef]
- Ohtake, F.; Baba, A.; Takada, I.; Okada, M.; Iwasaki, K.; Miki, H.; Takahashi, S.; Kouzmenko, A.; Nohara, K.; Chiba, T.; et al. Dioxin Receptor Is a Ligand-Dependent E3 Ubiquitin Ligase. Nature 2007, 446, 562–566. [Google Scholar] [CrossRef]
- Koga, R.; Yamamoto, M.; Ciftci, H.I.; Otsuka, M.; Fujita, M. Introduction of H2C2-Type Zinc-Binding Residues into HIV-2 Vpr Increases Its Expression Level. FEBS Open Bio 2018, 8, 146–153. [Google Scholar] [CrossRef] [PubMed]
- Scrima, A.; Konícková, R.; Czyzewski, B.K.; Kawasaki, Y.; Jeffrey, P.D.; Groisman, R.; Nakatani, Y.; Iwai, S.; Pavletich, N.P.; Thomä, N.H. Structural Basis of UV DNA-Damage Recognition by the DDB1-DDB2 Complex. Cell 2008, 135, 1213–1223. [Google Scholar] [CrossRef] [PubMed]
- Fischer, E.S.; Böhm, K.; Lydeard, J.R.; Yang, H.; Stadler, M.B.; Cavadini, S.; Nagel, J.; Serluca, F.; Acker, V.; Lingaraju, G.M.; et al. Structure of the DDB1-CRBN E3 Ubiquitin Ligase in Complex with Thalidomide. Nature 2014, 512, 49–53. [Google Scholar] [CrossRef] [PubMed]
- Bussiere, D.E.; Xie, L.; Srinivas, H.; Shu, W.; Burke, A.; Be, C.; Zhao, J.; Godbole, A.; King, D.; Karki, R.G.; et al. Structural Basis of Indisulam-Mediated RBM39 Recruitment to DCAF15 E3 Ligase Complex. Nat. Chem. Biol. 2020, 16, 15–23. [Google Scholar] [CrossRef]
- Fritz, J.V.; Didier, P.; Clamme, J.-P.; Schaub, E.; Muriaux, D.; Cabanne, C.; Morellet, N.; Bouaziz, S.; Darlix, J.-L.; Mély, Y.; et al. Direct Vpr-Vpr Interaction in Cells Monitored by Two Photon Fluorescence Correlation Spectroscopy and Fluorescence Lifetime Imaging. Retrovirology 2008, 5, 87. [Google Scholar] [CrossRef]
- Hornbeck, P.V.; Zhang, B.; Murray, B.; Kornhauser, J.M.; Latham, V.; Skrzypek, E. PhosphoSitePlus, 2014: Mutations, PTMs and Recalibrations. Nucleic Acids Res. 2015, 43, D512–D520. [Google Scholar] [CrossRef]
- Vanegas-Torres, C.A.; Schindler, M. HIV-1 Vpr Functions in Primary CD4(+) T Cells. Viruses 2024, 16, 420. [Google Scholar] [CrossRef]
- Boisvert, F.-M.; Ahmad, Y.; Gierliński, M.; Charrière, F.; Lamont, D.; Scott, M.; Barton, G.; Lamond, A.I. A Quantitative Spatial Proteomics Analysis of Proteome Turnover in Human Cells. Mol. Cell. Proteomics. 2012, 11, M111.011429. [Google Scholar] [CrossRef]
- Emmott, E.; AU-Goodfellow, I. Identification of Protein Interaction Partners in Mammalian Cells Using SILAC-Immunoprecipitation Quantitative Proteomics. JoVE 2014, e51656. [Google Scholar] [CrossRef]
- Desai, T.M.; Marin, M.; Sood, C.; Shi, J.; Nawaz, F.; Aiken, C.; Melikyan, G.B. Fluorescent Protein-Tagged Vpr Dissociates from HIV-1 Core after Viral Fusion and Rapidly Enters the Cell Nucleus. Retrovirology 2015, 12, 88. [Google Scholar] [CrossRef]
- Jáuregui, P.; Logue, E.C.; Schultz, M.L.; Fung, S.; Landau, N.R. Degradation of SAMHD1 by Vpx Is Independent of Uncoating. J. Virol. 2015, 89, 5701–5713. [Google Scholar] [CrossRef] [PubMed]
- Yáñez, A.; Bono, C.; Goodridge, H.S. Heterogeneity and Origins of Myeloid Cells. Curr. Opin. Hematol. 2022, 29, 201–208. [Google Scholar] [CrossRef] [PubMed]
- T Helper Cell Differentiation and Their Function; Sun, B. (Ed.) Springer Science + Business Media: Dordrecht, The Netherlands, 2014; Volume 841, ISBN 978-94-017-9487-9. [Google Scholar]
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Dobransky, A.; Root, M.; Hafner, N.; Marcum, M.; Sharifi, H.J. CRL4-DCAF1 Ubiquitin Ligase Dependent Functions of HIV Viral Protein R and Viral Protein X. Viruses 2024, 16, 1313. https://doi.org/10.3390/v16081313
Dobransky A, Root M, Hafner N, Marcum M, Sharifi HJ. CRL4-DCAF1 Ubiquitin Ligase Dependent Functions of HIV Viral Protein R and Viral Protein X. Viruses. 2024; 16(8):1313. https://doi.org/10.3390/v16081313
Chicago/Turabian StyleDobransky, Ashley, Mary Root, Nicholas Hafner, Matty Marcum, and H. John Sharifi. 2024. "CRL4-DCAF1 Ubiquitin Ligase Dependent Functions of HIV Viral Protein R and Viral Protein X" Viruses 16, no. 8: 1313. https://doi.org/10.3390/v16081313