The latency-associated nuclear antigen tethers the Kaposi's sarcoma-associated herpesvirus genome to host chromosomes in body cavity-based lymphoma cells

The latency-associated nuclear antigen tethers the Kaposi's sarcoma-associated herpesvirus genome to host chromosomes in body cavity-based lymphoma cells
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DOI:
10.1006/viro.1999.9999
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发表时间:
1999-11-25
期刊:
影响因子:
3.7
通讯作者:
Robertson, ES
Robertson, ES
中科院分区:
医学3区
文献类型:
--
作者:
Cotter, MA;Robertson, ES

文献摘要

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建立潜伏感染的病毒必须通过许多细胞世代将其DNA保持在宿主细胞核中。在这里,我们确定了一种新的机制,其中γ疱疹病毒卡波西肉瘤相关疱疹病毒(KSHV)可以实现这种持久性潜伏感染体腔淋巴瘤(BCBL)细胞。我们发现KSHV基因组DNA与宿主染色体相关,并与潜伏相关核抗原(拉娜)共定位。此外,KSHV基因组左端的区域与拉娜强烈结合,并且可以与拉娜共定位于宿主染色体。此外,我们发现拉娜与组蛋白H1在KSHV感染的BCBL细胞。我们提出,这种染色体协会的KSHV基因组介导的拉娜,并涉及一个拴系机制,通过该病毒附加体连接到宿主染色质,通过同时与宿主染色体蛋白,包括组蛋白H1和顺式作用KSHV DNA元件的相互作用。这种策略可以被其他病毒用于在感染细胞中建立潜伏期。(C)北京:科学出版社.
Viruses that establish latent infection must maintain their DNA in the host nucleus through many cellular generations. Here we identify a novel mechanism by which the gammaherpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) may achieve this persistence in latently infected body cavity-based lymphoma (BCBL) cells. We find that KSHV genomic DNA is associated with host chromosomes and colocalizes with the latency-associated nuclear antigen (LANA). Furthermore, a region at the left end of the KSHV genome binds strongly to LANA and can colocalize to the host chromosomes with LANA. Additionally, we found that LANA associates with histone H1 in KSHV-infected BCBL cells. We propose that this chromosomal association of the KSHV genome is mediated by LANA and involves a tethering mechanism by which viral episomes are linked to host chromatin through simultaneous interaction with host chromosomal proteins including histone H1 and cis-acting KSHV DNA elements. This strategy may be employed by other viruses in establishment of latency in the infected cells. (C) 1999 Academic Press.