Herpes simplex virus type 1 UL51 protein is involved in maturation and egress of virus particles
Herpes simplex virus type 1 UL51 protein is involved in maturation and egress of virus particles
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DOI：
10.1128/jvi.79.11.6947-6956.2005
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发表时间：
2005-06-01
影响因子：
5.4
通讯作者：
Nishiyama, Y
中科院分区：
文献类型：
--
作者：
Nozawa, N;Kawaguchi, Y;Nishiyama, Y
单纯疱疹病毒1型（HSV-1）的UL 51基因编码磷蛋白，其同源物在整个疱疹病毒家族中是保守的。最近，我们报道了UL 51蛋白在转染细胞中与高尔基体标记蛋白共定位，并且UL 51蛋白对高尔基体的靶向依赖于其N-末端9位半胱氨酸的棕榈酰化（N. Nozawa，T.大库库T. Koshizuka，Y. Yamauchi，T. Yoshikawa和Y. Nishiyama，J. Virol. 77：3204-3216，2003）。然而，其在HSV复制周期中的作用尚不清楚。在此，我们在HSV-1中产生了UL 51无效突变体（FDL 51）以揭示UL 51蛋白的功能。我们发现突变体噬斑的大小要小得多，最大滴度与野生型病毒相比降低了近100倍。电子显微镜检查表明，核衣壳的形成不受删除UL 51的影响，但从核周空间的病毒出口严重受损。在FDL 51感染的细胞中，在核周空间中观察到大量有包膜的核衣壳，但在细胞质中很少检测到有包膜的成熟病毒体以及细胞外成熟病毒体。通过重新插入UL 51基因，这些缺陷被完全挽救。这些结果表明，UL 51蛋白参与了HSV-1病毒颗粒在初始纯化步骤下游的成熟和排出。
The UL51 gene of herpes simplex virus type 1 (HSV-1) encodes a phosphoprotein whose homologs are conserved throughout the herpes virus family. Recently, we reported that UL51 protein colocalizes with Golgi marker proteins in transfected cells and that targeting of UL51 protein to the Golgi apparatus depends on palmitoylation of its N-terminal cysteine at position 9 (N. Nozawa, T. Daikoku, T. Koshizuka, Y. Yamauchi, T. Yoshikawa, and Y. Nishiyama, J. Virol. 77:3204-3216, 2003). However, its role in the HSV replication cycle was unknown. Here, we generated UL51-null mutants (FDL51) in HSV-1 to uncover the function of UL51 protein. We show that the mutant plaques were much smaller in size and that maximal titers were reduced nearly 100-fold compared to wild-type virus. Electron microscopy indicated that the formation of nucleocapsids was not affected by the deletion of UL51 but that viral egress from the perinuclear space was severely compromised. In FDL51-infected cells, a large number of enveloped nucleocapsids were observed in the perinuclear space, but enveloped mature virions in the cytoplasm, as well as extracellular mature virions, were rarely detected. These defects were fully rescued by reinsertion of the UL51 gene. These results indicate that UL51 protein is involved in the maturation and egress of HSV-1 virus particles downstream of the initial envelopment step.