US3 protein kinase of herpes simplex virus type 2 is required for the stability of the UL46-encoded tegument protein and its association with virus particles.
The herpes simplex virus (HSV) US3 gene encodes a serine/threonine protein kinase (PK). Although US3 PK is not essential for virus replication in cell culture, it plays an important role in the regulation of apoptosis in infected cells. However, the role of US3 PK in virus replication and pathogenicity is not well understood. The UL46 gene encodes virion tegument phosphoproteins, the properties and functions of which are poorly understood. In this study, it is shown that the UL46 protein of HSV type 2 (HSV-2) is affected strikingly by the presence of US3 PK. In the absence of US3 PK, UL46 protein was quite unstable, being much more susceptible to degradation. UL46 protein was undetectable in the extracellular virions of US3-deficient virus. Moreover, in vitro kinase assays using recombinant US3 PK show that UL46 protein is phosphorylated by the US3 PK, suggesting that UL46 can be a direct substrate for US3 PK in infected cells. Together, these findings shed new light on the physiological functions of US3 PK.
Matsuzaki
Akio
A
Department of Virology, Nagoya University Graduate School of Medicine, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Yamauchi
Yohei
Y
Department of Virology, Nagoya University Graduate School of Medicine, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Kato
Akihisa
A
Department of Virology, Nagoya University Graduate School of Medicine, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Goshima
Fumi
F
Department of Virology, Nagoya University Graduate School of Medicine, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Kawaguchi
Yasushi
Y
Department of Virology, Nagoya University Graduate School of Medicine, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Yoshikawa
Tetsushi
T
Department of Virology, Nagoya University Graduate School of Medicine, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Nishiyama
Yukihiro
Y
Department of Virology, Nagoya University Graduate School of Medicine, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D015967:Gene Expression Regulation, Viral; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000378:metabolism*
D010750:Phosphoproteins; D014764:Viral Proteins; D017346:Protein Serine-Threonine Kinases; C084395:US3 protein, Human herpesvirus 2