The herpes simplex virus type 2 protein icp10pk: a master of versatility

Smith, Cynthia C.

doi:10.2741/1738

Cited by 21 publications

(16 citation statements)

References 70 publications

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“…However, HSV RR differs from EBV RR in both protein size and function. Both contain RR activity, but HSV-encoded RR also contains kinase and antiapoptotic activity (27,31,37,38). However, the regions that encode these activities are not represented in the EBV RR gene.…”

Section: Discussionmentioning

confidence: 99%

The Epstein-Barr Virus (EBV) Deubiquitinating Enzyme BPLF1 Reduces EBV Ribonucleotide Reductase Activity

Whitehurst

Ning²,

Bentz³

et al. 2009

J Virol

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A newly discovered virally encoded deubiquitinating enzyme (DUB) is strictly conserved across the Herpesviridae. Epstein-Barr virus (EBV) BPLF1 encodes a tegument protein (3,149 amino acids) that exhibits deubiquitinating (DUB) activity that is lost upon mutation of the active-site cysteine. However, targets for the herpesviral DUBs have remained elusive. To investigate a predicted interaction between EBV BPLF1 and EBV ribonucleotide reductase (RR), a functional clone of the first 246 N-terminal amino acids of BPLF1 (BPLF1 1-246) was constructed. Immunoprecipitation verified an interaction between the small subunit of the viral RR2 and BPLF1 proteins. In addition, the large subunit (RR1) of the RR appeared to be ubiquitinated both in vivo and in vitro; however, ubiquitinated forms of the small subunit, RR2, were not detected. Ubiquitination of RR1 requires the expression of both subunits of the RR complex. Furthermore, coexpression of RR1 and RR2 with BPLF1 1-246 abolishes ubiquitination of RR1. EBV RR1, RR2, and BPLF1 1-246 colocalized to the cytoplasm in HEK 293T cells. Finally, expression of enzymatically active BPLF1 1-246 decreased RR activity, whereas a nonfunctional active-site mutant (BPLF1 C61S) had no effect. These results indicate that the EBV deubiquitinating enzyme interacts with, deubiquitinates, and influences the activity of the EBV RR. This is the first verified protein target of the EBV deubiquitinating enzyme.

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Section: Discussionmentioning

confidence: 99%

The Epstein-Barr Virus (EBV) Deubiquitinating Enzyme BPLF1 Reduces EBV Ribonucleotide Reductase Activity

Whitehurst

Ning²,

Bentz³

et al. 2009

J Virol

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“…The HIV-1 transactivator protein Tat activates the Ras/ERK signaling pathway to regulate cell cycle progression (28). The HSV-2 large subunit of ribonucleotide reductase (ICP10 protein kinase [PK]) binds the GDP/GTP exchange factor SOS (son of sevenless) and phosphorylates Ras-GAP to activate Ras, resulting in ERK activation (26). The protein kinase domain of HSV-2 ICP10 PK is required for ERK activation and inhibition of staurosporine-induced apoptosis (14).…”

Section: Discussionmentioning

confidence: 99%

Varicella-Zoster Virus ORF12 Protein Triggers Phosphorylation of ERK1/2 and Inhibits Apoptosis

Liu

Dowdell

et al. 2012

J Virol

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“…The remaining five novel virion components have wellcharacterized enzymatic functions in viral genome replication (pUL8 and pUL42), genome cleavage and encapsidation (pUL32), and ribonucleotide synthesis (pUL40 and pUL50) (40,45,58,119,121). Previously, virion incorporation of only three of these components has been studied.…”

Section: Vol 85 2011 Proteomic Analysis Of Prv Virions 6433mentioning

confidence: 99%

Proteomic Characterization of Pseudorabies Virus Extracellular Virions

Kramer

Greco

Enquist

et al. 2011

J Virol

131

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Pseudorabies virus (PRV), a member of the Alphaherpesvirinae, has a complex multilayered extracellular virion that is structurally conserved among other herpesviruses. PRV virions contain a double-stranded DNA genome within a proteinaceous capsid surrounded by the tegument, a layer of viral and cellular proteins. The envelope layer, which encloses the capsid and tegument, contains viral transmembrane proteins anchored in a phospholipid bilayer. The viral and host proteins contained within virions execute important functions during viral spread and pathogenesis, but a detailed understanding of the composition of PRV virions has been lacking. In this report, we present the first comprehensive proteomic characterization of purified PRV virions by mass spectrometry using two complementary approaches. To exclude proteins present in the extracellular medium that may nonspecifically associate with virions, we also analyzed virions treated with proteinase K and samples prepared from mock-infected cells. Overall, we identified 47 viral proteins associated with PRV virions, 40 of which were previously localized to the capsid, tegument, and envelope layers using traditional biochemical approaches. Additionally, we identified seven viral proteins that were previously undetected in virions, including pUL8, pUL20, pUL32, pUL40 (RR2), pUL42, pUL50 (dUTPase), and Rsp40/ICP22. Furthermore, although we did not enrich for posttranslational modifications, we detected phosphorylation of four virion proteins: pUL26, pUL36, pUL46, and pUL48. Finally, we identified 48 host proteins associated with PRV virions, many of which have known functions in important cellular pathways such as intracellular signaling, mRNA translation and processing, cytoskeletal dynamics, and membrane organization. This analysis extends previous work aimed at determining the composition of herpesvirus virions and provides novel insights critical for understanding the mechanisms underlying PRV entry, assembly, egress, spread, and pathogenesis.Pseudorabies virus (PRV) is a swine alphaherpesvirus closely related to the human pathogens herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) and varicella-zoster virus (VZV) (96,113). PRV is a pantropic, neuroinvasive virus with a broad host range and has been used extensively as a powerful tool for studying the architecture of mammalian neuronal circuits (35). The infectious particle of PRV, known as the mature virion, is a multilayered structure that is conserved among all herpesvirus families. At the core of the virion is a linear doublestranded DNA genome that is packaged within a proteinaceous capsid. The capsid is surrounded by a layer of viral and cellular proteins known as the tegument, which is enclosed within a phospholipid bilayer studded with viral transmembrane proteins and is known as the virion envelope (96, 113). To understand the fundamental mechanisms underlying PRV spread and pathogenesis, a comprehensive understanding of the subunits that compose the highly complex virion structure is necessary.The ini...

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The herpes simplex virus type 2 protein icp10pk: a master of versatility

Cited by 21 publications

References 70 publications

The Epstein-Barr Virus (EBV) Deubiquitinating Enzyme BPLF1 Reduces EBV Ribonucleotide Reductase Activity

The Epstein-Barr Virus (EBV) Deubiquitinating Enzyme BPLF1 Reduces EBV Ribonucleotide Reductase Activity

Varicella-Zoster Virus ORF12 Protein Triggers Phosphorylation of ERK1/2 and Inhibits Apoptosis

Proteomic Characterization of Pseudorabies Virus Extracellular Virions

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