| Structural highlights
Function
ICP0_HHV11 SUMO-targeted ubiquitin ligase that plays an essential role in nuclear antiviral defense evasion triggered by dsDNA viruses (PubMed:32001251). Acts during the initial stages of lytic infection and the reactivation of latent viral genome. Prevents the antiviral effect of nuclear bodies by degrading host PML, SP100 and MORC3 (PubMed:27440897, PubMed:34759314). Prevents antiviral response to viral DNA induced by IFI16 by degrading it. Additionally, inhibits host IRF3 nuclear signaling to prevent interferon production by the infected cells. Interestingly, the E3 ubiquitin ligase activity associated with the RING finger domain does not seem to be directly required to inhibit the activation of IRF3 but instead plays a critical role in modulating the cellular localization of ICP0. Upon reactivation of latent genome, suppresses the silencing of viral DNA by dissociating either HDAC1 or HDAC2 from the HDAC-RCOR1-REST-KDM1A complex localized at the ND10 structures and causes their dispersal. Two cellular histone ubiquitin ligases RNF8 and RNF168 are also targeted by ICP0 for degradation, leading to a loss of ubiquitinated forms of H2A, a relief of transcriptional repression, and the activation of latent viral genomes. Enhances the localization of host CCND3 to ND10 bodies that serve as precursors of replication compartments to enable efficient viral replication. Like many RING-finger E3 ubiquitin ligases, ICP0 can induce its own ubiquitination, an activity that promotes its instability due to its targeting to the 26S proteasome for degradation. ICP0 restricts this process by recruiting the cellular ubiquitin-specific protease USP7 that cleaves the anchored ubiquitin chains from ICP0, thereby promoting its stabilization.[1] [2] [3] [4] [5] [6] [7] [8] [9]
See Also
References
- ↑ Gu H, Liang Y, Mandel G, Roizman B. Components of the REST/CoREST/histone deacetylase repressor complex are disrupted, modified, and translocated in HSV-1-infected cells. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7571-6. PMID:15897453 doi:10.1073/pnas.0502658102
- ↑ Boutell C, Canning M, Orr A, Everett RD. Reciprocal activities between herpes simplex virus type 1 regulatory protein ICP0, a ubiquitin E3 ligase, and ubiquitin-specific protease USP7. J Virol. 2005 Oct;79(19):12342-54. PMID:16160161 doi:10.1128/JVI.79.19.12342-12354.2005
- ↑ Lilley CE, Chaurushiya MS, Boutell C, Landry S, Suh J, Panier S, Everett RD, Stewart GS, Durocher D, Weitzman MD. A viral E3 ligase targets RNF8 and RNF168 to control histone ubiquitination and DNA damage responses. EMBO J. 2010 Mar 3;29(5):943-55. PMID:20075863 doi:10.1038/emboj.2009.400
- ↑ Everett RD, Boutell C, McNair C, Grant L, Orr A. Comparison of the biological and biochemical activities of several members of the alphaherpesvirus ICP0 family of proteins. J Virol. 2010 Apr;84(7):3476-87. PMID:20106921 doi:10.1128/JVI.02544-09
- ↑ Paladino P, Collins SE, Mossman KL. Cellular localization of the herpes simplex virus ICP0 protein dictates its ability to block IRF3-mediated innate immune responses. PLoS One. 2010 Apr 29;5(4):e10428. PMID:20454685 doi:10.1371/journal.pone.0010428
- ↑ Chaurushiya MS, Lilley CE, Aslanian A, Meisenhelder J, Scott DC, Landry S, Ticau S, Boutell C, Yates JR 3rd, Schulman BA, Hunter T, Weitzman MD. Viral E3 ubiquitin ligase-mediated degradation of a cellular E3: viral mimicry of a cellular phosphorylation mark targets the RNF8 FHA domain. Mol Cell. 2012 Apr 13;46(1):79-90. PMID:22405594 doi:10.1016/j.molcel.2012.02.004
- ↑ Orzalli MH, DeLuca NA, Knipe DM. Nuclear IFI16 induction of IRF-3 signaling during herpesviral infection and degradation of IFI16 by the viral ICP0 protein. Proc Natl Acad Sci U S A. 2012 Oct 30;109(44):E3008-17. PMID:23027953 doi:10.1073/pnas.1211302109
- ↑ Sloan E, Orr A, Everett RD. MORC3, a Component of PML Nuclear Bodies, Has a Role in Restricting Herpes Simplex Virus 1 and Human Cytomegalovirus. J Virol. 2016 Sep 12;90(19):8621-33. PMID:27440897 doi:10.1128/JVI.00621-16
- ↑ Gaidt MM, Morrow A, Fairgrieve MR, Karr JP, Yosef N, Vance RE. Self-guarding of MORC3 enables virulence factor-triggered immunity. Nature. 2021 Dec;600(7887):138-142. PMID:34759314 doi:10.1038/s41586-021-04054-5
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