Kaposi's Sarcoma-Associated Herpesvirus Genome Replication, Partitioning, and Maintenance in Latency.

Kaposi's Sarcoma-Associated Herpesvirus Genome Replication, Partitioning, and Maintenance in Latency.
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DOI:
10.3389/fmicb.2012.00007
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发表时间:
2012
影响因子:
5.2
通讯作者:
Ueda K
Ueda K
中科院分区:
生物学2区
文献类型:
--
作者:
Ohsaki E;Ueda K

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卡波西氏肉瘤相关疱疹病毒(KSHV)被认为是γ-疱疹病毒亚家族的一种致癌成员。病毒通常在感染后建立延迟,作为默认的感染模式。病毒基因组通过招募宿主细胞复制机制,根据宿主细胞周期进行复制。在潜伏表达的病毒因子中,LANA在病毒基因组复制、分裂和维持中起着关键作用。LANA与末端重复序列(TR)中的两个LANA结合位点(LBS1/2)结合,在潜伏期病毒基因组复制中是必不可少的。核基质区域似乎是一个重要的复制位点,因为LANA和细胞复制因子聚集在那里,并通过其与LBS的结合活性在潜伏期(i- p)招募病毒复制原点。KSHV ori-P由LBS和32bp的富含gc的片段(32GC)组成。虽然有报道称LANA通过与细胞起源识别复合体(ORCs)的相互作用将细胞前复制复合体(pre-RC)如起源识别复合体(ORCs)招募到ori-P,但这一机制并不能完全解释32GC的需求。另一方面,关于病毒基因组的分割和维持的报道很少。LANA与多种染色体蛋白相互作用,包括Brd2/RING3,核心组蛋白,如H2A/H2B和组蛋白H1等。LANA使KSHV基因组分配和维持的详细分子机制仍然不清楚。通过整合迄今为止报道的关于KSHV基因组复制、分区和维持潜伏期的研究结果,我们将总结我们现在所知道的,讨论还有什么问题需要回答,并确定下一步需要做什么来理解病毒复制、分区和维持策略的潜在机制。
Kaposi’s sarcoma-associated herpesvirus (KSHV) is thought to be an oncogenic member of the γ-herpesvirus subfamily. The virus usually establishes latency upon infection as a default infection pattern. The viral genome replicates according to the host cell cycle by recruiting the host cellular replication machinery. Among the latently expressing viral factors, LANA plays pivotal roles in viral genome replication, partitioning, and maintenance. LANA binds with two LANA-binding sites (LBS1/2) within a terminal repeat (TR) sequence and is indispensable for viral genome replication in latency. The nuclear matrix region seems to be important as a replication site, since LANA as well as cellular replication factors accumulate there and recruit the viral replication origin in latency (ori-P) by its binding activity to LBS. KSHV ori-P consists of LBS followed by a 32-bp GC-rich segment (32GC). Although it has been reported that LANA recruits cellular pre-replication complexes (pre-RC) such as origin recognition complexes (ORCs) to the ori-P through its interaction with ORCs, this mechanism does not account completely for the requirement of the 32GC. On the other hand, there are few reports about the partitioning and maintenance of the viral genome. LANA interacts with many kinds of chromosomal proteins, including Brd2/RING3, core histones, such as H2A/H2B and histone H1, and so on. The detailed molecular mechanisms by which LANA enables KSHV genome partitioning and maintenance still remain obscure. By integrating the findings reported thus far on KSHV genome replication, partitioning, and maintenance in latency, we will summarize what we know now, discuss what questions remain to be answered, and determine what needs to be done next to understand the mechanisms underlying viral replication, partitioning, and maintenance strategy.
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