scholarly journals Tyrosine Phosphorylation of Bovine Herpesvirus 1 Tegument Protein VP22 Correlates with the Incorporation of VP22 into Virions

2001 ◽  
Vol 75 (19) ◽  
pp. 9010-9017 ◽  
Author(s):  
Xiaodi Ren ◽  
Jerome S. Harms ◽  
Gary A. Splitter
Keyword(s):  
Tyrosine Phosphorylation ◽  
Phosphorylation Site ◽  
Bovine Herpesvirus ◽  
Structural Proteins ◽  
Tegument Protein ◽  
Bovine Herpesvirus 1 ◽  
C Terminus ◽  
Herpesvirus 1 ◽  
Protein Vp22 ◽  
Viral Structural Proteins

ABSTRACT Tyrosine phosphorylation has been shown to play a role in the replication of several herpesviruses. In this report, we demonstrate that bovine herpesvirus 1 infection triggered tyrosine phosphorylation of proteins with molecular masses similar to those of phosphorylated viral structural proteins. One of the tyrosine-phosphorylated viral structural proteins was the tegument protein VP22. A tyrosine 38-to-phenylalanine mutation totally abolished the phosphorylation of VP22 in transfected cells. However, construction of a VP22 tyrosine 38-to-phenylalanine mutant virus demonstrated that VP22 was still phosphorylated but that the phosphorylation site may change to the C terminus rather than be in the N terminus as in wild-type VP22. In addition, the loss of VP22 tyrosine phosphorylation correlated with reduced incorporation of VP22 compared to that of envelope glycoprotein D in the mutant viruses but not with the amount of VP22 produced during virus infection. Our data suggest that tyrosine phosphorylation of VP22 plays a role in virion assembly.

Intercellular trafficking of the major tegument protein VP22 of bovine herpesvirus-1 and its application to improve a DNA vaccine

2005 ◽  
Vol 151 (5) ◽  
pp. 985-993 ◽  
Author(s):  
C. F. Zheng ◽  
R. Brownlie ◽  
D. Y. Huang ◽  
L. A. Babiuk ◽  
S. van Drunen Littel-van den Hurk
Keyword(s):  
Dna Vaccine ◽  
Bovine Herpesvirus ◽  
Tegument Protein ◽  
Bovine Herpesvirus 1 ◽  
Intercellular Trafficking ◽  
Herpesvirus 1 ◽  
Protein Vp22

scholarly journals The Infected Cell Protein 0 Encoded by Bovine Herpesvirus 1 (bICP0) Induces Degradation of Interferon Response Factor 3 and, Consequently, Inhibits Beta Interferon Promoter Activity

2007 ◽  
Vol 81 (7) ◽  
pp. 3077-3086 ◽  
Author(s):  
Kazima Saira ◽  
You Zhou ◽  
Clinton Jones
Keyword(s):  
Ring Finger ◽  
Bovine Herpesvirus ◽  
Productive Infection ◽  
Interferon Response ◽  
Response Factor ◽  
Bovine Herpesvirus 1 ◽  
Protein Levels ◽  
Beta Interferon ◽  
C Terminus ◽  
Herpesvirus 1

ABSTRACT The ICP0 protein (bICP0) encoded by bovine herpesvirus 1 is the major viral regulatory protein because it stimulates all viral promoters and, consequently, productive infection. Like other ICP0 analogues encoded by Alphaherpesvirinae subfamily members, bICP0 contains a zinc RING finger near its amino terminus that is necessary for activating transcription, regulating subcellular localization, and inhibiting interferon-dependent transcription. In this study, we discovered that sequences near the C terminus, and the zinc RING finger, are necessary for inhibiting the human beta interferon (IFN-β) promoter. In contrast to herpes simplex virus type 1-encoded ICP0, bICP0 reduces interferon response factor 3 (IRF3), but not IRF7, protein levels in transiently transfected cells. The zinc RING finger and sequences near the C terminus are necessary for bICP0-induced degradation of IRF3. A proteasome inhibitor, lactacystin, interfered with bICP0-induced degradation of IRF3, suggesting that bICP0, directly or indirectly, targets IRF3 for proteasome-dependent degradation. IRF3, but not IRF7, is not readily detectable in the nuclei of productively infected bovine cells during the late stages of infection. In the context of productive infection, IRF3 and IRF7 are detected in the nucleus at early times after infection. At late times after infection, IRF7, but not IRF3, is still detectable in the nuclei of infected cells. Collectively, these studies suggest that the ability of bICP0 to reduce IRF3 protein levels is important with respect to disarming the IFN response during productive infection.

scholarly journals Characterization of nuclear localization and export signals of the major tegument protein VP8 of bovine herpesvirus-1

Virology ◽  
2004 ◽  
Vol 324 (2) ◽  
pp. 327-339 ◽  
Author(s):  
Chunfu Zheng ◽  
Robert Brownlie ◽  
Lorne A Babiuk ◽  
Sylvia van Drunen Littel-van den Hurk
Keyword(s):  
Nuclear Localization ◽  
Bovine Herpesvirus ◽  
Tegument Protein ◽  
Bovine Herpesvirus 1 ◽  
Herpesvirus 1

scholarly journals Bovine herpesvirus 1 tegument protein UL21 plays critical roles in viral secondary envelopment and cell-to-cell spreading

Oncotarget ◽  
2017 ◽  
Vol 8 (55) ◽  
pp. 94462-94480 ◽  
Author(s):  
Farzana Shahin ◽  
Sohail Raza ◽  
Kui Yang ◽  
Changmin Hu ◽  
Yingyu Chen ◽  
...  
Keyword(s):  
Bovine Herpesvirus ◽  
Cell Spreading ◽  
Tegument Protein ◽  
Bovine Herpesvirus 1 ◽  
Herpesvirus 1

scholarly journals US3 Kinase-Mediated Phosphorylation of Tegument Protein VP8 Plays a Critical Role in the Cellular Localization of VP8 and Its Effect on the Lipid Metabolism of Bovine Herpesvirus 1-Infected Cells

2019 ◽  
Vol 93 (6) ◽  
Author(s):  
Kuan Zhang ◽  
Tara Donovan ◽  
Soumya Sucharita ◽  
Robert Brownlie ◽  
Marlene Snider ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Cellular Localization ◽  
Bovine Herpesvirus ◽  
Tegument Protein ◽  
Cytoplasmic Localization ◽  
Cellular Lipid ◽  
Bovine Herpesvirus 1 ◽  
Cholesterol Levels ◽  
Infected Cells ◽  
Herpesvirus 1

ABSTRACTBovine herpesvirus 1 (BoHV-1) infects bovine species, causing respiratory infections, genital disorders and abortions. VP8 is the most abundant tegument protein of BoHV-1 and is critical for virus replication in cattle. In this study, the cellular transport of VP8 in BoHV-1-infected cells and its ability to alter the cellular lipid metabolism were investigated. A viral kinase, US3, was found to be involved in regulating these processes. In the early stages of infection VP8 was localized in the nucleus. Subsequently, presumably after completion of its role in the nucleus, VP8 was translocated to the cytoplasm. When US3 was deleted or the essential US3 phosphorylation site of VP8 was mutated in BoHV-1, the majority of VP8 was localized in the nuclei of infected cells. This suggests that phosphorylation by US3 may be critical for cytoplasmic localization of VP8. Eventually, the cytoplasmic VP8 was accumulated in thecis-Golgi apparatus but not in thetrans-Golgi network, implying that VP8 was not involved in virion transport toward and budding from the cell membrane. VP8 caused lipid droplet (LD) formation in the nuclei of transfected cells and increased cellular cholesterol levels. Lipid droplets were not found in the nuclei of BoHV-1-infected cells when VP8 was cytoplasmic in the presence of US3. However, when US3 was deleted or phosphorylation residues in VP8 were mutated, nuclear VP8 and LDs appeared in BoHV-1-infected cells. The total cholesterol level was increased in BoHV-1-infected cells but not in ΔUL47-BoHV-1-infected cells, further supporting a role for VP8 in altering the cellular lipid metabolism during infection.IMPORTANCENuclear localization signals (NLSs) and nuclear export signals (NESs) are important elements directing VP8 to the desired locations in the BoHV-1-infected cell. In this study, a critical regulator that switches the nuclear and cytoplasmic localization of VP8 in BoHV-1-infected cells was identified. BoHV-1 used viral kinase US3 to regulate the cellular localization of VP8. Early during BoHV-1 infection VP8 was localized in the nucleus, where it performs various functions; once US3 was expressed, phosphorylated VP8 was cytoplasmic and ultimately accumulated in thecis-Golgi apparatus, presumably to be incorporated into virions. The Golgi localization of VP8 was only observed in virus-infected cells and not in US3-cotransfected cells, suggesting that this is mediated by other viral factors. Interestingly, VP8 was shown to cause increased cholesterol levels, which is a novel function for VP8 and a potential strategy to supply lipid for viral replication.

The bovine herpesvirus-1 major tegument protein, VP8, interacts with host HSP60 concomitant with deregulation of mitochondrial function

2019 ◽  
Vol 261 ◽  
pp. 37-49 ◽  
Author(s):  
Sharmin Afroz ◽  
Robert Brownlie ◽  
Michel Fodje ◽  
Sylvia van Drunen Littel-van den Hurk
Keyword(s):  
Mitochondrial Function ◽  
Bovine Herpesvirus ◽  
Tegument Protein ◽  
Bovine Herpesvirus 1 ◽  
Herpesvirus 1

scholarly journals VP8, the Major Tegument Protein of Bovine Herpesvirus-1, Is Partially Packaged during Early Tegument Formation in a VP22-Dependent Manner

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1854
Author(s):  
Soumya Sucharita ◽  
Kuan Zhang ◽  
Sylvia van Drunen Littel-van den Hurk
Keyword(s):  
Bovine Herpesvirus ◽  
Tegument Protein ◽  
Phosphorylation Sites ◽  
Dependent Manner ◽  
Bovine Herpesvirus 1 ◽  
Transfected Cells ◽  
Nuclear Lamin ◽  
Infected Cells ◽  
Herpesvirus 1 ◽  
Dependent Mechanism

Bovine herpesvirus-1 (BoHV-1) is a major cause of rhinotracheitis and vulvovaginitis in cattle. VP8, the major tegument protein of BoHV-1, is essential for viral replication in the host. VP8 is phosphorylated by the viral kinase US3, mediating its translocation to the cytoplasm. VP8 remains nuclear when not phosphorylated. Interestingly, VP8 has a significant presence in mature BoHV-1YmVP8, in which the VP8 phosphorylation sites are mutated. This suggests that VP8 might be packaged during primary envelopment of BoHV-1. This was investigated by mass spectrometry and Western blotting, which showed VP8, as well as VP22, to be constituents of the primary enveloped virions. VP8 and VP22 were shown to interact via co-immunoprecipitation experiments, in both BoHV-1-infected and VP8-transfected cells. VP8 and VP22 also co-localised with one another and with nuclear lamin-associated protein 2 in BoHV-1-infected cells, suggesting an interaction between VP8 and VP22 in the perinuclear region. In cells infected with VP22-deleted BoHV-1 (BoHV-1ΔUL49), VP8 was absent from the primary enveloped virions, implying that VP22 might be critical for the early packaging of VP8. In conclusion, a novel VP22-dependent mechanism for packaging of VP8 was identified, which may be responsible for a significant amount of VP8 in the viral particle.

scholarly journals Regulation and Function of Phosphorylation on VP8, the Major Tegument Protein of Bovine Herpesvirus 1

2015 ◽  
Vol 89 (8) ◽  
pp. 4598-4611 ◽  
Author(s):  
Kuan Zhang ◽  
Sharmin Afroz ◽  
Robert Brownlie ◽  
Marlene Snider ◽  
Sylvia van Drunen Littel-van den Hurk
Keyword(s):  
Life Cycle ◽  
Virus Replication ◽  
Active Sites ◽  
Bovine Herpesvirus ◽  
Kinase Assay ◽  
Tegument Protein ◽  
Bovine Herpesvirus 1 ◽  
Herpesvirus 1 ◽  
And Function

ABSTRACTThe major tegument protein of bovine herpesvirus 1 (BoHV-1), VP8, is essential for virus replication in cattle. VP8 is phosphorylatedin vitroby casein kinase 2 (CK2) and BoHV-1 unique short protein 3 (US3). In this study, VP8 was found to be phosphorylated in both transfected and infected cells but was detected as a nonphosphorylated form in mature virions. This suggests that phosphorylation of VP8 is strictly controlled during different stages of the viral life cycle. The regulation and function of VP8 phosphorylation by US3 and CK2 were further analyzed. Anin vitrokinase assay, site-directed mutagenesis, and liquid chromatography-mass spectrometry were used to identify the active sites for US3 and CK2. The two kinases phosphorylate VP8 at different sites, resulting in distinct phosphopeptide patterns. S16is a primary phosphoreceptor for US3, and it subsequently triggers phosphorylation at S32. CK2 has multiple active sites, among which T107appears to be the preferred residue. Additionally, CK2 consensus motifs in the N terminus of VP8 are essential for phosphorylation. Based on these results, a nonphosphorylated VP8 mutant was constructed and used for further studies. In transfected cells phosphorylation was not required for nuclear localization of VP8. Phosphorylated VP8 appeared to recruit promyelocytic leukemia (PML) protein and to remodel the distribution of PML in the nucleus; however, PML protein did not show an association with nonphosphorylated VP8. This suggests that VP8 plays a role in resisting PML-related host antiviral defenses by redistributing PML protein and that this function depends on the phosphorylation of VP8.IMPORTANCEThe progression of VP8 phosphorylation over time and its function in BoHV-1 replication have not been characterized. This study demonstrates that activation of S16initiates further phosphorylation at S32by US3. Additionally, VP8 is phosphorylated by CK2 at several residues, with T107having the highest level of phosphorylation. Evidence for a difference in the phosphorylation status of VP8 in host cells and mature virus is presented for the first time. Phosphorylation was found to be a critical modification, which enables VP8 to attract and to redistribute PML protein in the nucleus. This might promote viral replication through interference with a PML-mediated antiviral defense. This study provides new insights into the regulation of VP8 phosphorylation and suggests a novel, phosphorylation-dependent function for VP8 in the life cycle of BoHV-1, which is important in view of the fact that VP8 is essential for virus replicationin vivo.

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