人疱疹病毒8编码的胸苷激酶和磷酸转移酶同源物使细胞对更昔洛韦敏感。
Human herpesvirus 8-encoded thymidine kinase and phosphotransferase homologues confer sensitivity to ganciclovir.
作者信息
Cannon J S, Hamzeh F, Moore S, Nicholas J, Ambinder R F
机构信息
Departments of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
出版信息
J Virol. 1999 Jun;73(6):4786-93. doi: 10.1128/JVI.73.6.4786-4793.1999.
Abstract
Human herpesvirus 8 (HHV-8) sensitivity to the nucleoside analog ganciclovir (GCV) suggests the presence of a virally encoded kinase that catalyzes the initial phosphorylation of GCV. Analysis of the HHV-8 genome identified two candidate kinases: proteins encoded by open reading frame (ORF) 21, with homology to the herpesvirus thymidine kinases (TK), and ORF 36, with homology to the herpesvirus phosphotransferases (PT). Experiments presented here show that both ORF 21 and ORF 36 encode GCV kinase activities as demonstrated by GCV phosphorylation and GCV-mediated cell death. In both regards the PT homologue ORF 36 was more active than the TK homologue ORF 21. ORF 21, but not ORF 36, weakly sensitized cells to killing by penciclovir. Neither ORF sensitized cells to killing by (E)-5-(2-bromovinyl)-2'-deoxyuridine.
摘要
人类疱疹病毒8型（HHV - 8）对核苷类似物更昔洛韦（GCV）敏感，这表明存在一种病毒编码的激酶，可催化GCV的初始磷酸化。对HHV - 8基因组的分析确定了两种候选激酶：由开放阅读框（ORF）21编码的蛋白，与疱疹病毒胸苷激酶（TK）具有同源性；以及ORF 36编码的蛋白，与疱疹病毒磷酸转移酶（PT）具有同源性。此处展示的实验表明，ORF 21和ORF 36均编码GCV激酶活性，这通过GCV磷酸化和GCV介导的细胞死亡得以证明。在这两方面，PT同源物ORF 36比TK同源物ORF 21更具活性。ORF 21而非ORF 36，使细胞对喷昔洛韦杀伤的敏感性略有增加。两种ORF均未使细胞对（E）-5 -（2 - 溴乙烯基）-2'-脱氧尿苷的杀伤敏感。
相似文献
1
Human herpesvirus 8-encoded thymidine kinase and phosphotransferase homologues confer sensitivity to ganciclovir.
J Virol. 1999 Jun;73(6):4786-93. doi: 10.1128/JVI.73.6.4786-4793.1999.
2
Human herpesvirus 8 open reading frame 21 is a thymidine and thymidylate kinase of narrow substrate specificity that efficiently phosphorylates zidovudine but not ganciclovir.
J Virol. 2000 Jan;74(2):684-92. doi: 10.1128/jvi.74.2.684-692.2000.
3
The Epstein-Barr virus (EBV)-encoded protein kinase, EBV-PK, but not the thymidine kinase (EBV-TK), is required for ganciclovir and acyclovir inhibition of lytic viral production.
J Virol. 2010 May;84(9):4534-42. doi: 10.1128/JVI.02487-09. Epub 2010 Feb 24.
4
Selective abolishment of pyrimidine nucleoside kinase activity of herpes simplex virus type 1 thymidine kinase by mutation of alanine-167 to tyrosine.
Mol Pharmacol. 2000 Dec;58(6):1326-32. doi: 10.1124/mol.58.6.1326.
5
The U69 gene of human herpesvirus 6 encodes a protein kinase which can confer ganciclovir sensitivity to baculoviruses.
J Virol. 1999 Apr;73(4):3284-91. doi: 10.1128/JVI.73.4.3284-3291.1999.
6
Substrate specificity and molecular modelling of the feline herpesvirus-1 thymidine kinase.
Arch Virol. 2008;153(3):495-505. doi: 10.1007/s00705-007-0021-6. Epub 2008 Jan 15.
7
Spectrum of activity and mechanisms of resistance of various nucleoside derivatives against gammaherpesviruses.
Antimicrob Agents Chemother. 2014 Dec;58(12):7312-23. doi: 10.1128/AAC.03957-14. Epub 2014 Sep 29.
8
A designed equine herpes thymidine kinase (EHV4 TK) variant improves ganciclovir-induced cell-killing.
Biochem Pharmacol. 2014 Feb 1;87(3):435-44. doi: 10.1016/j.bcp.2013.11.011. Epub 2013 Dec 4.
9
VP22 enhanced intercellular trafficking of HSV thymidine kinase reduced the level of ganciclovir needed to cause suicide cell death.
J Gene Med. 2001 Mar-Apr;3(2):145-52. doi: 10.1002/jgm.164.
10
The Epstein-Barr virus thymidine kinase does not phosphorylate ganciclovir or acyclovir and demonstrates a narrow substrate specificity compared to the herpes simplex virus type 1 thymidine kinase.
Antimicrob Agents Chemother. 1998 Nov;42(11):2923-31. doi: 10.1128/AAC.42.11.2923.
引用本文的文献
1
Tapioca: a platform for predicting de novo protein-protein interactions in dynamic contexts.
Nat Methods. 2024 Mar;21(3):488-500. doi: 10.1038/s41592-024-02179-9. Epub 2024 Feb 15.
2
Kaposi's Sarcoma-Associated Herpesvirus ORF21 Enhances the Phosphorylation of MEK and the Infectivity of Progeny Virus.
Int J Mol Sci. 2023 Jan 8;24(2):1238. doi: 10.3390/ijms24021238.
3
Self-Repairing Herpesvirus Saimiri Deletion Variants.
Viruses. 2022 Jul 13;14(7):1525. doi: 10.3390/v14071525.
4
Therapeutic Perspectives in the Systemic Treatment of Kaposi's Sarcoma.
Cancers (Basel). 2022 Jan 18;14(3):484. doi: 10.3390/cancers14030484.
5
Proteomic approaches to investigate gammaherpesvirus biology and associated tumorigenesis.
Adv Virus Res. 2021;109:201-254. doi: 10.1016/bs.aivir.2020.10.001. Epub 2020 Nov 9.
6
Characteristics and outcomes of KSHV-associated multicentric Castleman disease with or without other KSHV diseases.
Blood Adv. 2021 Mar 23;5(6):1660-1670. doi: 10.1182/bloodadvances.2020004058.
7
Kaposi's Sarcoma-Associated Herpesvirus Processivity Factor, ORF59, Binds to Canonical and Linker Histones, and Its Carboxy Terminus Is Dispensable for Viral DNA Synthesis.
J Virol. 2021 Feb 24;95(6). doi: 10.1128/JVI.02169-20.
8
Bovine Leukemia Virus Infection Affects Host Gene Expression Associated with DNA Mismatch Repair.
Pathogens. 2020 Oct 30;9(11):909. doi: 10.3390/pathogens9110909.
9
5-Ethynyl-2'-deoxycytidine and 5-ethynyl-2'-deoxyuridine are differentially incorporated in cells infected with HSV-1, HCMV, and KSHV viruses.
J Biol Chem. 2020 May 1;295(18):5871-5890. doi: 10.1074/jbc.RA119.012378. Epub 2020 Mar 23.
10
Induction of Kaposi's Sarcoma-Associated Herpesvirus-Encoded Thymidine Kinase (ORF21) by X-Box Binding Protein 1.
J Virol. 2020 Feb 14;94(5). doi: 10.1128/JVI.01555-19.
本文引用的文献
1
The Epstein-Barr virus thymidine kinase does not phosphorylate ganciclovir or acyclovir and demonstrates a narrow substrate specificity compared to the herpes simplex virus type 1 thymidine kinase.
Antimicrob Agents Chemother. 1998 Nov;42(11):2923-31. doi: 10.1128/AAC.42.11.2923.
2
Functional regions of the human cytomegalovirus protein pUL97 involved in nuclear localization and phosphorylation of ganciclovir and pUL97 itself.
J Gen Virol. 1998 Sep;79 ( Pt 9):2105-12. doi: 10.1099/0022-1317-79-9-2105.
3
Characterization of the human cytomegalovirus UL97 gene product as a virion-associated protein kinase.
Arch Virol. 1998;143(6):1223-32. doi: 10.1007/s007050050370.
4
Antiviral drug susceptibility of human herpesvirus 8.
Antimicrob Agents Chemother. 1997 Dec;41(12):2754-6. doi: 10.1128/AAC.41.12.2754.
5
In search of a selective antiviral chemotherapy.
Clin Microbiol Rev. 1997 Oct;10(4):674-93. doi: 10.1128/CMR.10.4.674.
6
Phosphorylation of aciclovir, ganciclovir, penciclovir and S2242 by the cytomegalovirus UL97 protein: a quantitative analysis using recombinant vaccinia viruses.
Antiviral Res. 1997 Sep;36(1):35-42. doi: 10.1016/s0166-3542(97)00034-x.
7
In vitro antiviral drug sensitivity of the Kaposi's sarcoma-associated herpesvirus.
AIDS. 1997 Sep;11(11):1327-32. doi: 10.1097/00002030-199711000-00006.
8
Sensitivity of Kaposi's sarcoma-associated herpesvirus replication to antiviral drugs. Implications for potential therapy.
J Clin Invest. 1997 May 1;99(9):2082-6. doi: 10.1172/JCI119380.
9
A Bcl-2 homolog encoded by Kaposi sarcoma-associated virus, human herpesvirus 8, inhibits apoptosis but does not heterodimerize with Bax or Bak.
Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):690-4. doi: 10.1073/pnas.94.2.690.
10
The human cytomegalovirus UL97 protein is a protein kinase that autophosphorylates on serines and threonines.
J Virol. 1997 Jan;71(1):405-11. doi: 10.1128/JVI.71.1.405-411.1997.
Zotero 插件