Matsuzaki Akio, Yamauchi Yohei, Kato Akihisa, Goshima Fumi, Kawaguchi Yasushi, Yoshikawa Tetsushi, Nishiyama Yukihiro
Department of Virology, Nagoya University Graduate School of Medicine, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
J Gen Virol. 2005 Jul;86(Pt 7):1979-1985. doi: 10.1099/vir.0.80949-0.
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.
单纯疱疹病毒(HSV)的US3基因编码一种丝氨酸/苏氨酸蛋白激酶(PK)。尽管US3 PK对于病毒在细胞培养中的复制并非必不可少,但它在调节受感染细胞的凋亡中起重要作用。然而,US3 PK在病毒复制和致病性中的作用尚未得到充分了解。UL46基因编码病毒体被膜磷蛋白,其特性和功能了解甚少。在本研究中,结果表明,2型单纯疱疹病毒(HSV-2)的UL46蛋白受US3 PK的存在影响显著。在没有US3 PK的情况下,UL46蛋白相当不稳定,更容易被降解。在US3缺陷病毒的细胞外病毒体中检测不到UL46蛋白。此外,使用重组US3 PK进行的体外激酶分析表明,UL46蛋白被US3 PK磷酸化,这表明UL46可能是受感染细胞中US3 PK的直接底物。这些发现共同为US3 PK的生理功能提供了新的线索。