Oligomerization of ICP4 and rearrangement of heat shock proteins may be important for herpes simplex virus type 1 prereplicative site formation
Oligomerization of ICP4 and rearrangement of heat shock proteins may be important for herpes simplex virus type 1 prereplicative site formation
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DOI：
10.1128/jvi.00455-08
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发表时间：
2008-07-01
影响因子：
5.4
通讯作者：
Weller, Sandra K.
中科院分区：
文献类型：
--
作者：
Livingston, Christine M.;DeLuca, Neal A.;Weller, Sandra K.
单纯疱疹病毒1型（HSV-1）DNA复制发生在细胞核中通过一系列蛋白质支架中间体的有序过程形成的复制区室中。在病毒基因组进入细胞核后，可以在邻近核结构域10（ND 10）样体的位置检测到含有ICP 4的核蛋白复合物。然后通过病毒E3泛素连接酶ICP 0破坏ND 10。我们以前曾报道，ND 10样体解离后，可以观察到ICP 8的弥漫染色模式，然而，使用更敏感的染色方法，我们现在报告，除了弥漫染色，ICP 8可以检测到在微小的病灶相邻的ICP 4病灶。ICP 8微灶含有UL 9和解旋酶-引发酶复合物的组分。HSV感染还导致热休克同源蛋白70（Hsc 70）和20 S蛋白酶体重组为病毒诱导的富含伴侣蛋白（VICE）的结构域。在这份报告中，我们表明，VICE结构域是不同的，但邻近的ICP 4核蛋白复合物和ICP 8微灶。在用编码不能在DNA上寡聚化的突变蛋白的ICP 4突变病毒感染的细胞中，未检测到ICP 8微灶;然而，仍然可以形成VICE结构域。这些结果表明，ICP 4在病毒DNA上的寡聚化可能是ICP 8微灶形成所必需的，但不是宿主细胞伴侣重组成VICE结构域所必需的。
Herpes simplex virus type 1 (HSV-1) DNA replication occurs in replication compartments that form in the nucleus by an ordered process involving a series of protein scaffold intermediates. Following entry of viral genomes into the nucleus, nucleoprotein complexes containing ICP4 can be detected at a position adjacent to nuclear domain 10 (ND10)-like bodies. ND10s are then disrupted by the viral E3 ubiquitin ligase ICP0. We have previously reported that after the dissociation of ND10-like bodies, ICP8 could be observed in a diffuse staining pattern; however, using more sensitive staining methods, we now report that in addition to diffuse staining, ICP8 can be detected in tiny foci adjacent to ICP4 foci. ICP8 microfoci contain UL9 and components of the helicase-primase complex. HSV infection also results in the reorganization of the heat shock cognate protein 70 (Hsc70) and the 20S proteasome into virus-induced chaperone-enriched (VICE) domains. In this report we show that VICE domains are distinct but adjacent to the ICP4 nucleoprotein complexes and the ICP8 microfoci. In cells infected with an ICP4 mutant virus encoding a mutant protein that cannot oligomerize on DNA, ICP8 microfoci are not detected; however, VICE domains could still be formed. These results suggest that oligomerization of ICP4 on viral DNA may be essential for the formation of ICP8 microfoci but not for the reorganization of host cell chaperones into VICE domains.