Abstract
Cullin-RING ubiquitin ligases (CRLs) are efficient and diverse toolsets of the cells to regulate almost every biological process. However, these characteristics have also been usurped by many viruses to optimize for their replication. CRLs are often at the forefront of the arms races in the coevolution of viruses and hosts. Here we review the modes of actions and functional consequences of viral manipulations of host cell CRLs. We also discuss the therapeutic applications to target these viral manipulations for treating viral infections.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- CRL:
-
Cullin-RING ubiquitin ligases
- Cul1-5:
-
Cullin 1-5
- DCAF:
-
DDB1-Cul4-associated factors
- HBV:
-
Hepatitis B virus
- HIV:
-
Human immunodeficiency virus
- KSHV:
-
Kaposi’s sarcoma-associated herpesvirus
- RSV:
-
Respiratory syncytial virus
- SCF:
-
SKP1-Cullin1-Fbox E3 ligase
- SR:
-
Substrate receptor
References
Ahn J et al (2012) 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 287:12550–12558
Ajay AK, Meena AS, Bhat MK (2012) Human papillomavirus 18 E6 inhibits phosphorylation of p53 expressed in HeLa cells. Cell Biosci 2:2–2
Ashizawa A et al (2012) The ubiquitin system and Kaposi’s sarcoma-associated herpesvirus. Front Microbiol 3:66–66
Bai C et al (1996) SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell 86:263–274. https://doi.org/10.1016/s0092-8674(00)80098-7
Barry M, Fruh K (2006) Viral modulators of cullin RING ubiquitin ligases: culling the host defense. Sci STKE 2006:pe21. https://doi.org/10.1126/stke.3352006pe21
Bennett RP, Salter JD, Smith HCA (2018) New class of antiretroviral enabling innate immunity by protecting APOBEC3 from HIV Vif-dependent degradation. Trends Mol Med 24:507–520
Cen et al (2010) Small molecular compounds inhibit HIV-1 replication through specifically stabilizing APOBEC3G. J Biol Chem 285:16546–16562. https://doi.org/10.1074/jbc.M109.085308
Chaudhuri R, Lindwasser OW, Smith W, Hurley JH, Bonifacino JS (2007) Downregulation of CD4 by human immunodeficiency virus type 1 Nef is dependent on Clathrin and involves direct interaction of Nef with the AP2 Clathrin adaptor. J Virol 81:3877–3890
Chen ZJ (2005) Ubiquitin signaling in the NF-κB pathway. Nat Cell Biol 7:758
Collins DR, Collins KL (2014) HIV-1 accessory proteins adapt cellular adaptors to facilitate immune evasion. PLoS Pathog 10
Daugherty MD, Malik HS (2012) Rules of engagement: molecular insights from host-virus arms races. Annu Rev Genet 46:677–700. https://doi.org/10.1146/annurev-genet-110711-155522
Davis K, Morelli M, Patton J (2017) Rotavirus NSP1 requires casein kinase II-mediated phosphorylation for hijacking of Cullin-RING ligases. 8. https://doi.org/10.1128/mBio.01213-17
Davis KA, Patton JT (2017) Shutdown of interferon signaling by a viral-hijacked E3 ubiquitin ligase. Microbial Cell 4:387–389
Decorsiere A et al (2016) Hepatitis B virus X protein identifies the Smc5/6 complex as a host restriction factor. Nature 531:386–389
Deshaies RJ, Joazeiro CA (2009) RING domain E3 ubiquitin ligases. Annu Rev Biochem 78:399–434. https://doi.org/10.1146/annurev.biochem.78.101807.093809
Dube M, Bego MG, Paquay C, Cohen EA (2010) Modulation of HIV-1-host interaction: role of the Vpu accessory protein. Retrovirology 7:114–114
Elliott J et al (2007) Respiratory syncytial virus NS1 protein degrades STAT2 by using the Elongin-Cullin E3 ligase. J Virol 81:3428–3436. https://doi.org/10.1128/JVI.02303-06
Ellis M et al (1999) Degradation of p27 Kip cdk inhibitor triggered by Kaposi’s sarcoma virus cyclin-cdk6 complex. EMBO J 18:644–653
Evans DT, Serra-Moreno R, Singh RK, Guatelli JC (2010) BST-2/tetherin: a new component of the innate immune response to enveloped viruses. Trends Microbiol 18:388–396. https://doi.org/10.1016/j.tim.2010.06.010
Feldman RM, Correll CC, Kaplan KB, Deshaies RJ (1997) A complex of Cdc4p, Skp1p, and Cdc53p/cullin catalyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p. Cell 91:221–230. https://doi.org/10.1016/s0092-8674(00)80404-3
Frescas D, Pagano M (2008) Deregulated proteolysis by the F-box proteins SKP2 and beta-TrCP: tipping the scales of cancer. Nat Rev Cancer 8:438–449. https://doi.org/10.1038/nrc2396
Gastaldello S et al (2010) A deneddylase encoded by Epstein-Barr virus promotes viral DNA replication by regulating the activity of cullin-RING ligases. Nat Cell Biol 12:351–361. https://doi.org/10.1038/ncb2035
Graff JW, Ettayebi K, Hardy ME (2009) Rotavirus NSP1 inhibits NFκB activation by inducing proteasome-dependent degradation of β-TrCP: a novel mechanism of IFN antagonism. PLoS Pathog 5:e1000280
Greenwood EJD et al (2019) Promiscuous targeting of cellular proteins by Vpr drives systems-level proteomic remodeling in HIV-1 infection. Cell Rep 27:1579–1596 e1577. https://doi.org/10.1016/j.celrep.2019.04.025
Guo Y et al (2014) Structural basis for hijacking CBF-beta and CUL5 E3 ligase complex by HIV-1 Vif. Nature 505:229–233. https://doi.org/10.1038/nature12884
Harper JW, Tan MK (2012) Understanding cullin-RING E3 biology through proteomics-based substrate identification. Mol Cell Proteomics MCP 11:1541–1550. https://doi.org/10.1074/mcp.R112.021154
Harris RS et al (2003) DNA deamination mediates innate immunity to retroviral infection. Cell 113:803–809. https://doi.org/10.1016/s0092-8674(03)00423-9
He J et al (1995) 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 69:6705–6711
Hershko A, Ciechanover A (1998) The ubiquitin system. Annu Rev Biochem 67:425–479
Hrecka K et al (2011) Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein. Nature 474:658–661
Huang X, Dixit VM (2016) Drugging the undruggables: exploring the ubiquitin system for drug development. Cell Res 26:484–498
Huttenhain R et al (2019) ARIH2 Is a Vif-Dependent regulator of CUL5-Mediated APOBEC3G degradation in HIV infection. Cell Host Microbe 26:86–99 e87. https://doi.org/10.1016/j.chom.2019.05.008
Jager S et al (2012) Vif hijacks CBF-β to degrade APOBEC3G and promote HIV-1 infection. Nature 481:371–375
Jia D et al (2010) Influenza virus non-structural protein 1 (NS1) disrupts interferon signaling. PLoS One 5:e13927. https://doi.org/10.1371/journal.pone.0013927
Jin J et al (2004) Systematic analysis and nomenclature of mammalian F-box proteins. Genes Dev 18:2573–2580. https://doi.org/10.1101/gad.1255304
Kaelin WG Jr (2002) Molecular basis of the VHL hereditary cancer syndrome. Nat Rev Cancer 2:673–682. https://doi.org/10.1038/nrc885
Ke Q, Costa M (2006) Hypoxia-Inducible Factor-1 (HIF-1). Mol Pharmacol 70:1469–1480
Kilani MM, Mohammed KA, Nasreen N, Tepper RS, Antony VB (2004) RSV causes HIF-1α stabilization via NO release in primary bronchial epithelial cells. Inflammation 28:245–251
Kim DY et al (2013) CBFbeta stabilizes HIV Vif to counteract APOBEC3 at the expense of RUNX1 target gene expression. Mol Cell 49:632–644. https://doi.org/10.1016/j.molcel.2012.12.012
Laguette N et al (2011) SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature 474:654–657. https://doi.org/10.1038/nature10117
Lahouassa H et al (2012) SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates. Nat Immunol 13:223–228. https://doi.org/10.1038/ni.2236
Lan KH et al (2007) HCV NS5A inhibits interferon-alpha signaling through suppression of STAT1 phosphorylation in hepatocyte-derived cell lines. J Hepatol 46:759–767. https://doi.org/10.1016/j.jhep.2006.11.013
Lecossier D, Bouchonnet F, Clavel F, Hance AJ (2003) Hypermutation of HIV-1 DNA in the absence of the Vif protein. Science 300:1112. https://doi.org/10.1126/science.1083338
Li T, Chen X, Garbutt KC, Zhou P, Zheng N (2006) Structure of DDB1 in complex with a paramyxovirus V protein: viral hijack of a propeller cluster in ubiquitin ligase. Cell 124:105–117
Lim ES, Emerman M (2011) HIV: going for the watchman. Nature 474:587–588. https://doi.org/10.1038/474587a
Liu J et al (2007) Kaposi’s sarcoma-associated herpesvirus LANA protein downregulates nuclear glycogen synthase kinase 3 activity and consequently blocks differentiation. J Virol 81:4722–4731. https://doi.org/10.1128/JVI.02548-06
Liu Y et al (2019) Proteomic profiling of HIV-1 infection of human CD4(+) T cells identifies PSGL-1 as an HIV restriction factor. Nat Microbiol 4:813–825. https://doi.org/10.1038/s41564-019-0372-2
Lutz LM, Pace CR, Arnold MM (2016) Rotavirus NSP1 associates with components of the cullin RING ligase family of E3 ubiquitin ligases. J Virol 90:6036–6048
Mahon C, Krogan NJ, Craik CS, Pick E (2014) Cullin E3 ligases and their rewiring by viral factors. Biomol Ther 4:897–930. https://doi.org/10.3390/biom4040897
Malim MH, Bieniasz PD (2012) HIV restriction factors and mechanisms of evasion. Cold Spring Harb Perspect Med 2:a006940. https://doi.org/10.1101/cshperspect.a006940
Mangeat B et al (2003) Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature 424:99–103. https://doi.org/10.1038/nature01709
Margottin F et al (1998) A novel human WD protein, h-beta TrCp, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif. Mol Cell 1:565–574
Matheson NJ et al (2015) Cell surface proteomic map of HIV infection reveals antagonism of amino acid metabolism by Vpu and Nef. Cell Host Microbe 18:409–423
McDougall WM, Perreira JM, Reynolds EC, Brass AL (2018) CRISPR genetic screens to discover host-virus interactions. Curr Opin Virol 29:87–100. https://doi.org/10.1016/j.coviro.2018.03.007
Murphy CM et al (2016) Hepatitis B virus X protein promotes degradation of SMC5/6 to enhance HBV replication. Cell Rep 16:2846–2854
Nathans RS et al (2008) Small-molecule inhibition of HIV-1 Vif. Nat Biotechnol 26:1187–1192
Neil SJ, Zang T, Bieniasz PD (2008) Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 451:425–430. https://doi.org/10.1038/nature06553
Nowinska K, Ciesielska U, Podhorska-Okolow M, Dziegiel P (2017) The role of human papillomavirus in oncogenic transformation and its contribution to the etiology of precancerous lesions and cancer of the larynx: a review. Adv Clin Exp Med 26:539–547. https://doi.org/10.17219/acem/67461
Perez-Caballero D et al (2009) Tetherin inhibits HIV-1 release by directly tethering virions to cells. Cell 139:499–511. https://doi.org/10.1016/j.cell.2009.08.039
Pery E et al (2015) Identification of a novel HIV-1 inhibitor targeting Vif-dependent degradation of human APOBEC3G protein. J Biol Chem 290:10504–10517
Rodrigues L et al (2009) Termination of NF-kappaB activity through a gammaherpesvirus protein that assembles an EC5S ubiquitin-ligase. EMBO J 28:1283–1295. https://doi.org/10.1038/emboj.2009.74
Roy N, Pacini G, Berlioz-Torrent C, Janvier K (2014) Mechanisms underlying HIV-1 Vpu-mediated viral egress. Front Microbiol 5:177. https://doi.org/10.3389/fmicb.2014.00177
Sarikas A, Hartmann T, Pan ZQ (2011) The cullin protein family. Genome Biol 12:220. https://doi.org/10.1186/gb-2011-12-4-220
Sauter D, Kirchhoff F (2018) Multilayered and versatile inhibition of cellular antiviral factors by HIV and SIV accessory proteins. Cytokine Growth Factor Rev 40:3–12. https://doi.org/10.1016/j.cytogfr.2018.02.005
Schneider WM, Chevillotte MD, Rice CM (2014) Interferon-stimulated genes: a complex web of host defenses. Annu Rev Immunol 32:513–545. https://doi.org/10.1146/annurev-immunol-032713-120231
Schwartz AL, Ciechanover A (1999) The ubiquitin-proteasome pathway and pathogenesis of human diseases. Annu Rev Med 50:57–74. https://doi.org/10.1146/annurev.med.50.1.57
Sen A, Feng N, Ettayebi K, Hardy ME, Greenberg HB (2009) IRF3 inhibition by rotavirus NSP1 is host cell and virus strain dependent but independent of NSP1 proteasomal degradation. J Virol 83:10322–10335
Shah PS, Wojcechowskyj JA, Eckhardt M, Krogan NJ (2015) Comparative mapping of host-pathogen protein-protein interactions. Curr Opin Microbiol 27:62–68. https://doi.org/10.1016/j.mib.2015.07.008
Sharkey et al (2019) HIV-1 escape from small-molecule antagonism of Vif. MBio 26:e00144–19. https://doi.org/10.1128/mBio.00144-19
Sheehy AM, Gaddis NC, Choi JD, Malim MH (2002) Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 418:646–650
Skaar JR, Pagan JK, Pagano M (2013) Mechanisms and function of substrate recruitment by F-box proteins. Nat Rev Mol Cell Biol 14:369–381. https://doi.org/10.1038/nrm3582
Skowyra D, Craig KL, Tyers M, Elledge SJ, Harper JW (1997) F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex. Cell 91:209–219. https://doi.org/10.1016/s0092-8674(00)80403-1
Stogios PJ, Downs GS, Jauhal JJ, Nandra SK, Prive GG (2005) Sequence and structural analysis of BTB domain proteins. Genome Biol 6:R82. https://doi.org/10.1186/gb-2005-6-10-r82
Sugden SM, Cohen EA (2015) Attacking the supply lines: HIV-1 restricts alanine uptake to prevent T cell activation. Cell Host Microbe 18:514–517
Surjit M, Varshney B, Lal SK (2012) The ORF2 glycoprotein of hepatitis E virus inhibits cellular NF-κB activity by blocking ubiquitination mediated proteasomal degradation of IκBα in human hepatoma cells. BMC Biochem 13:7–7
Van Damme N et al (2008) The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein. Cell Host Microbe 3:245–252. https://doi.org/10.1016/j.chom.2008.03.001
Vigan R, Neil SJ (2010) Determinants of tetherin antagonism in the transmembrane domain of the human immunodeficiency virus type 1 Vpu protein. J Virol 84:12958–12970. https://doi.org/10.1128/JVI.01699-10
Votteler J, Schubert US (2008) Ubiquitin ligases as therapeutic targets in HIV-1 infection. Expert Opin Ther Targets 12:131–143
Weekes MP et al (2014) Quantitative temporal viromics: an approach to investigate host-pathogen interaction. Cell 157:1460–1472. https://doi.org/10.1016/j.cell.2014.04.028
White EA et al (2012) Systematic identification of interactions between host cell proteins and E7 oncoproteins from diverse human papillomaviruses. Proc Natl Acad Sci U S A 109:E260–E267
Yim E, Park J (2005) The role of HPV E6 and E7 Oncoproteins in HPV-associated cervical carcinogenesis. Cancer Res Treat 37:319–324
Yu X et al (2003) Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex. Science 302:1056–1060. https://doi.org/10.1126/science.1089591
Zhang H et al (2003) The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA. Nature 424:94–98
Zhang W, Du J, Evans SL, Yu Y, Yu XF (2011) T-cell differentiation factor CBF-beta regulates HIV-1 Vif-mediated evasion of host restriction. Nature 481:376–379. https://doi.org/10.1038/nature10718
Zheng N, Shabek N (2017) Ubiquitin ligases: structure, function, and regulation. Annu Rev Biochem 86:129–157. https://doi.org/10.1146/annurev-biochem-060815-014922
Zhou M et al (2017) Synthesis, biological evaluation and molecular docking study of N-(2-methoxyphenyl)-6-((4-nitrophenyl)sulfonyl)benzamide derivatives as potent HIV-1 Vif antagonists. Eur J Med Chem 129:310–324. https://doi.org/10.1016/j.ejmech.2017.01.010
Zhuang M et al (2009) Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases. Mol Cell 36:39–50
Zuo T et al (2012) Small-molecule inhibition of human immunodeficiency virus type 1 replication by targeting the interaction between Vif and ElonginC. J Virol 86:5497–5507. https://doi.org/10.1128/JVI.06957-11
Acknowledgments
We apologize to colleagues whose works are not included in this review due to space limitation. This work was supported by the China National Funds for Excellent Young Scientists (31722030)Â and a grant (Grant No. 31670777) from the National Natural Science Foundation of China and from the Beijing Advanced Innovation Center for Structural Biology.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Liu, Y., Tan, X. (2020). Viral Manipulations of the Cullin-RING Ubiquitin Ligases. In: Sun, Y., Wei, W., Jin, J. (eds) Cullin-RING Ligases and Protein Neddylation. Advances in Experimental Medicine and Biology, vol 1217. Springer, Singapore. https://doi.org/10.1007/978-981-15-1025-0_7
Download citation
DOI: https://doi.org/10.1007/978-981-15-1025-0_7
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-15-1024-3
Online ISBN: 978-981-15-1025-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)