PDF(Pubmed)
Abstract：
Human adenoviruses (HAdV) belong to a small DNA tumor virus family that continues as valuable models in understanding the viral strategies of usurping cell growth regulation. A number of HAdV type 2/5 early viral gene products interact with a variety of cellular proteins to build a conducive environment that promotes viral replication. Here we show that HBO1 (Histone Acetyltransferase Binding to ORC1), a member of the MYST histone acetyltransferase (HAT) complex (also known as KAT7 and MYST2) that acetylates most of the histone H3 lysine 14, is essential for HAdV5 growth. HBO1/MYST2/KAT7 HAT complexes are critical for a variety of cellular processes including control of cell proliferation. In HBO1 downregulated human cells, HAdV5 infection results in reduced expression of E1A and other viral early genes, virus growth is also reduced significantly. Importantly, HBO1 downregulation reduced H3 lysine 14 acetylation at viral promoters during productive infection, likely driving reduced viral gene expression. HBO1 was also associated with viral promoters during infection and co-localized with viral replication centers in the nuclei of infected cells. In transiently transfected cells, overexpression of E1A along with HBO1 stimulated histone acetyltransferase activity of HBO1. E1A also co-immunoprecipitated with HBO1 in transiently transfected cells. In summary, our results demonstrate that HAdV recruits the HBO1 HAT complex to aid in viral replication.
摘要：
人类腺病毒（HAdV）属于一个小DNA肿瘤病毒家族，在理解篡夺细胞生长调节的病毒策略方面继续作为有价值的模型。许多HAdV2/5型早期病毒基因产物与多种细胞蛋白相互作用以建立促进病毒复制的有利环境。在这里，我们显示HBO1(组蛋白乙酰转移酶与ORC1的结合)，MYST组蛋白乙酰转移酶（HAT）复合物（也称为KAT7和MYST2）的成员，将大部分组蛋白H3赖氨酸14乙酰化，对于HAdV5生长至关重要。HBO1/MYST2/KAT7HAT复合物对于多种细胞过程(包括细胞增殖的控制)是关键的。在HBO1下调的人体细胞中，HAdV5感染导致E1A和其他病毒早期基因表达降低，病毒生长也显著减少。重要的是,在生产性感染期间，HBO1下调降低了病毒启动子处的H3赖氨酸14乙酰化，可能驱动降低病毒基因表达。HBO1在感染期间也与病毒启动子相关，并与病毒复制中心共同定位在感染细胞的核中。在瞬时转染的细胞中，E1A和HBO1的过表达刺激了HBO1的组蛋白乙酰转移酶活性。E1A也在瞬时转染的细胞中与HBO1共免疫沉淀。总之,我们的结果表明，HAdV招募HBO1HAT复合物来帮助病毒复制。
