scholarly journals Human Cytomegalovirus Nuclear Capsids Associate with the Core Nuclear Egress Complex and the Viral Protein Kinase pUL97

Viruses ◽  
2018 ◽  
Vol 10 (1) ◽  
pp. 35 ◽  
Author(s):  
Jens Milbradt ◽  
Eric Sonntag ◽  
Sabrina Wagner ◽  
Hanife Strojan ◽  
Christina Wangen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Human Cytomegalovirus ◽  
Viral Protein ◽  
The Core ◽  
Nuclear Egress ◽  
Viral Protein Kinase

scholarly journals The ULb' Region of the Human Cytomegalovirus Genome Confers an Increased Requirement for the Viral Protein Kinase UL97

2013 ◽  
Vol 87 (11) ◽  
pp. 6359-6376 ◽  
Author(s):  
D. Wang ◽  
G. Li ◽  
M. Schauflinger ◽  
C. C. Nguyen ◽  
E. D. Hall ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Human Cytomegalovirus ◽  
Viral Protein ◽  
Viral Protein Kinase

scholarly journals An Epistatic Relationship between the Viral Protein Kinase UL97 and the UL133-UL138 Latency Locus during the Human Cytomegalovirus Lytic Cycle

2014 ◽  
Vol 88 (11) ◽  
pp. 6047-6060 ◽  
Author(s):  
G. Li ◽  
M. Rak ◽  
C. C. Nguyen ◽  
M. Umashankar ◽  
F. D. Goodrum ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Human Cytomegalovirus ◽  
Viral Protein ◽  
Lytic Cycle ◽  
Viral Protein Kinase

scholarly journals Inhibitors of human cytomegalovirus replication drastically reduce the activity of the viral protein kinase pUL97

2001 ◽  
Vol 82 (6) ◽  
pp. 1439-1450 ◽  
Author(s):  
Manfred Marschall ◽  
Matthias Stein-Gerlach ◽  
Martina Freitag ◽  
Regina Kupfer ◽  
Miriam van den Bogaard ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Phosphorylation ◽  
Human Cytomegalovirus ◽  
Viral Protein ◽  
Kinase Activity ◽  
Kinase Inhibitors ◽  
Critical Role ◽  
Protein Kinase Inhibitors ◽  
Viral Protein Kinase ◽  
Exact Function

The UL97-encoded protein kinase (pUL97) of human cytomegalovirus (HCMV) plays a critical role in the control of virus replication. Deletion of the UL97 gene results in a drastic reduction in the replication efficiency. Although the exact function of pUL97 remains unclear and its sensitivity to specific inhibitors is speculative, protein kinase inhibitors of the indolocarbazole class are effective inhibitors of cytomegalovirus. Based on the phosphorylation of ganciclovir (GCV), a novel quantification system for pUL97 kinase activity was established: the phosphorylated form of GCV exerts an easily quantifiable cytotoxic effect in transfected cells. Importantly, the addition of indolocarbazole compounds, Gö6976 and NGIC-I, which were highly effective at nanomolar concentrations while other protein kinase inhibitors were not, led to a significant reduction of pUL97 kinase activity. It was also demonstrated that a catalytically inactive mutant of pUL97, K355M, and a GCV-resistant mutant, M460I, were both negative for GCV phosphorylation, although protein phosphorylation remained detectable for the latter mutant. In vitro kinase assays were used to confirm the levels of pUL97-mediated phosphorylation recorded. To generate a tool for screening large numbers of putative inhibitors that preferentially interfere with GCV as well as protein phosphorylation, pUL97-expressing cell clones with stable pUL97 kinase activity were selected. This study demonstrates that certain indolocarbazole compounds are potent pUL97 inhibitors and, therefore, represent novel candidates for antiviral drugs that target viral protein kinase functions.

scholarly journals CTL Are Inactivated by Herpes Simplex Virus-Infected Cells Expressing a Viral Protein Kinase

2003 ◽  
Vol 171 (12) ◽  
pp. 6733-6741 ◽  
Author(s):  
Derek D. Sloan ◽  
George Zahariadis ◽  
Christine M. Posavad ◽  
Nichlos T. Pate ◽  
Steven J. Kussick ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Protein Kinase ◽  
Viral Protein ◽  
Viral Protein Kinase ◽  
Infected Cells ◽  
Simplex Virus

scholarly journals The Human Cytomegalovirus UL97 Protein Kinase, an Antiviral Drug Target, Is Required at the Stage of Nuclear Egress

2003 ◽  
Vol 77 (2) ◽  
pp. 905-914 ◽  
Author(s):  
Paula M. Krosky ◽  
Moon-Chang Baek ◽  
Donald M. Coen
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Virus Infection ◽  
Human Cytomegalovirus ◽  
Antiviral Drug ◽  
Virus Yield ◽  
Wild Type Virus ◽  
Wild Type ◽  
Viral Dna ◽  
Nuclear Egress

ABSTRACT Human cytomegalovirus encodes an unusual protein kinase, UL97, that activates the established antiviral drug ganciclovir and is specifically inhibited by a new antiviral drug, maribavir. We used maribavir and a UL97 null mutant, which is severely deficient in viral replication, to determine what stage of virus infection critically requires UL97. Compared with wild-type virus, there was little or no decrease in immediate-early gene expression, viral DNA synthesis, late gene expression, or packaging of viral DNA into nuclease-resistant structures in mutant-infected or maribavir-treated cells under conditions where the virus yield was severely impaired. Electron microscopy studies revealed similar proportions of various capsid forms, including DNA-containing capsids, in the nuclei of wild-type- and mutant-infected cells. However, capsids were rare in the cytoplasm of mutant-infected or maribavir-treated cells; the magnitudes of these decreases in cytoplasmic capsids were similar to those for virus yield. Thus, genetic and pharmacological evidence indicates that UL97 is required at the stage of infection when nucleocapsids exit from the nucleus (nuclear egress), and this poorly understood stage of virus infection can be targeted by antiviral drugs. Understanding UL97 function and maribavir action should help elucidate this interesting biological process and help identify new antiviral drug targets for an important pathogen in immunocompromised patients.

scholarly journals A viral protein kinase drug target for tumors?

2018 ◽  
Vol 128 (6) ◽  
pp. 2197-2198 ◽  
Author(s):  
Richard F. Ambinder
Keyword(s):  
Protein Kinase ◽  
Viral Protein ◽  
Drug Target ◽  
Viral Protein Kinase
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