Identification of a target protein of US3 protein kinase of herpes simplex virus type 2

Daikoku, Tohru; Kurachi, Ryo; Tsurumi, Tatsuya; Nishiyama, Yukihiro

doi:10.1099/0022-1317-75-8-2065

Cited by 36 publications

(22 citation statements)

References 18 publications

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“…Purves et al (1991) demonstrated that US3-encoded PK of HSV-1 is involved in the phosphorylation ofa 30K protein encoded by UL34. Daikoku et al (1994) reported that HSV-2 US3-encoded PK may be involved in the phosphorylation of the US9-encoded tegument phosphoprotein. From our experiments we hypothesize that the decrease in virulence of US3 PK mutants may be caused by an accumulation of progeny virus in the perinuclear space of the host cells.…”

Section: Short Communicationmentioning

confidence: 99%

The US3-encoded protein kinase from pseudorabies virus affects egress of virions from the nucleus

Wagenaar¹,

Pol²,

Peeters³

et al. 1995

Journal of General Virology

108

113

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We examined the influence of inactivation of various genes located in the unique short (Us) region of pseudorabies virus on virus replication and assembly in porcine nasal mucosa explant cultures. The following strains were used: the virulent wild-type strain NIA-3, and strains derived from NIA-3 containing a mutation inactivating the genes encoding either the US3-encoded protein kinase (PK), gG, gD, gI, gE, the 28 kDa (' 28K') protein (single mutant), or the 28K and 11 kDa ('11K') proteins (double mutant). In addition a wild-type rescuant was used, which was generated by marker rescue from a PK mutant. All virus strains infected nasal epithelium and had invaded the stroma after approximately 24 h. The morphogenesis in nasal epithelium cells of two PK-mutants showed the most striking differences compared to the parent NIA-3 strain and the other mutant strains. The changes could be ascribed to the US3-encoded PK because the rescue mutant showed a similar morphogenesis to wild-type NIA-3. The transmembrane transport of the PKmutants was impaired at the outer nuclear membrane which resulted in an accumulation of virions in the perinuclear space. These results suggest that proteins, phosphorylated by the US3-encoded PK, are involved in debudding of virus particles at the outer nuclear membrane. This defect in the transport of the US3 mutant probably explains their reduced replication in vitro. The gG-, gD , gI , gEL 28K-and 11K-mutant strains showed minor or no changes in viral assembly. Thus the reported decreased virulence of the gD , gF and gE mutants was, in contrast to that of the PKmutants, not associated with clear alterations in morphogenesis.

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Section: Short Communicationmentioning

confidence: 99%

The US3-encoded protein kinase from pseudorabies virus affects egress of virions from the nucleus

Wagenaar¹,

Pol²,

Peeters³

et al. 1995

Journal of General Virology

108

113

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“…Although several viral proteins have been shown to be substrates for the US3 PK (Daikoku et al, 1994 ;Purves et al, 1991), there is no evidence that they are involved in blocking apoptosis. In summary, our present results strongly suggest a role for the US3 PK in blocking apoptosis in vivo, although the possible involvement of an additional mutation cannot completely be ruled out.…”

mentioning

confidence: 99%

US3 protein kinase of herpes simplex virus type 2 plays a role in protecting corneal epithelial cells from apoptosis in infected mice.

Asano

Honda

Goshima

et al. 1999

Journal of General Virology

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To clarify the biological role of US3 protein kinase of herpes simplex virus type 2 (HSV-2) in vivo, the expression of the viral antigen, the appearance of apoptotic bodies and DNA fragmentation were examined immunohistologically after corneal infection of mice with three different kinds of HSV-2 strain 186 : the wild-type virus, a US3-deficient mutant (L1BR1) and its revertant (L1B N 11). In both wild-type 186-and L1B N 11-infected mice, viral antigen was diffusely found in the corneal epithelium ; no apoptotic changes were detected in the epithelial cells. Whereas, in L1BR1-infected mice, HSV-immunoreactivity was localized around the virus-inoculated sites, and a large number of apoptotic bodies were observed in the corneal epithelium with dual-positive reactions for both HSVimmunostaining and TUNEL staining. These results suggest that the US3 protein kinase plays an important role in protecting HSV-2-infected cells from apoptotic death in vivo.

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“…It also drives the phosphorylation of the VZV ORF32 protein in VZV-infected cells (49). The targets of the VZV ORF66 protein kinase are not known, but the homologous protein kinases in alphaherpesviruses (sometimes referred to as the US3 protein kinases) seem to target multiple and varied proteins specific for each virus (5,6,38,55,62). Recent evidence has indicated that HSV-1 US3 protein kinase also prevents apo-ptosis following infection and thus may target cellular proteins (38).…”

mentioning

confidence: 99%

Nuclear Accumulation of IE62, the Varicella-Zoster Virus (VZV) Major Transcriptional Regulatory Protein, Is Inhibited by Phosphorylation Mediated by the VZV Open Reading Frame 66 Protein Kinase

Kinchington

Fite

Turse

2000

J Virol

109

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IE62, the major transcriptional activator protein encoded by varicella-zoster virus (VZV), locates to the nucleus when expressed in transfected cells. We show here that cytoplasmic forms of IE62 accumulate in transfected and VZV-infected cells as the result of the protein kinase activity associated with VZV open reading frame 66 (ORF66). Expression of the ORF66 protein kinase but not the VZV ORF47 protein kinase impaired the ability of coexpressed IE62 to transactivate promoter-reporter constructs. IE62 that was coexpressed with the ORF66 protein accumulated predominantly in the cytoplasm, whereas the normal nuclear localization of other proteins was not affected by the ORF66 protein. In cells infected with VZV, IE62 accumulated in the cytoplasm at late times of infection, whereas in cells infected with a VZV recombinant unable to express ORF66 protein (ROka66S), IE62 was completely nuclear. Point mutations introduced into the predicted serine/ threonine catalytic domain and ATP binding domain of ORF66 abrogated its ability to influence IE62 nuclear localization, indicating that the protein kinase activity was required. The region of IE62 that was targeted by ORF66 was mapped to amino acids 602 to 733. IE62 peptides containing this region were specifically phosphorylated in cells coexpressing the ORF66 protein kinase and in cells infected with wild-type VZV but were not phosphorylated in cells infected with ROka66S. We conclude that the ORF66 protein kinase phosphorylates IE62 to induce its cytoplasmic accumulation, most likely by inhibiting IE62 nuclear import.

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Identification of a target protein of US3 protein kinase of herpes simplex virus type 2

Cited by 36 publications

References 18 publications

The US3-encoded protein kinase from pseudorabies virus affects egress of virions from the nucleus

The US3-encoded protein kinase from pseudorabies virus affects egress of virions from the nucleus

US3 protein kinase of herpes simplex virus type 2 plays a role in protecting corneal epithelial cells from apoptosis in infected mice.

Nuclear Accumulation of IE62, the Varicella-Zoster Virus (VZV) Major Transcriptional Regulatory Protein, Is Inhibited by Phosphorylation Mediated by the VZV Open Reading Frame 66 Protein Kinase

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