Inhibition of the lytic cycle of Kaposi's sarcoma-associated herpesvirus by cohesin factors following de novo infection

Inhibition of the lytic cycle of Kaposi's sarcoma-associated herpesvirus by cohesin factors following de novo infection
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DOI:
10.1016/j.virol.2017.09.001
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发表时间:
2017-12-01
期刊:
影响因子:
3.7
通讯作者:
Papp, Bernadett
Papp, Bernadett
中科院分区:
医学3区
文献类型:
--
作者:
Toth, Zsolt;Smindak, Richard J.;Papp, Bernadett

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感染后卡波西肉瘤相关疱疹病毒(KSHV)潜伏期的建立是一个多步骤的过程,在此过程中,多梳蛋白被募集到KSHV基因组上,这对于潜伏期内全基因组范围内抑制抒情基因至关重要。引人注目的是,在多梳蛋白结合到KSHV基因组上之前,在感染的早期阶段,只有一部分裂解基因瞬时表达,这就提出了一个问题,即在感染的最初几个小时,是什么限制了裂解基因的表达。在这里,我们证明了CTCF和粘着蛋白染色质组织因子在从头感染期间结合polycombs之前被迅速招募到病毒基因组中,但只有粘着蛋白是全基因组抑制抒情基因所必需的。我们建议,cohesin是建立KSHV潜伏期所需的启动抑制抒情基因感染后,这是一个重要的步骤,在人类的持续感染。
Establishment of Kaposi's sarcoma-associated herpesvirus (KSHV) latency following infection is a multistep process, during which polycomb proteins are recruited onto the KSHV genome, which is crucial for the genome-wide repression of lyric genes during latency. Strikingly, only a subset of lytic genes are expressed transiently in the early phase of infection prior to the binding of polycomb proteins onto the KSHV genome, which raises the question what restricts lyric gene expression in the first hours of infection. Here, we demonstrate that both CTCF and cohesin chromatin organizing factors are rapidly recruited to the viral genome prior to the binding of polycombs during de novo infection, but only cohesin is required for the genome-wide inhibition of lyric genes. We propose that cohesin is required for the establishment of KSHV latency by initiating the repression of lyric genes following infection, which is an essential step in persistent infection of humans.