Herpes simplex virus type 1 tegument protein VP22 interacts with TAR proteins and inhibits nucleosome assembly but not regulation of histone acetylation by INHAT
Herpes simplex virus type 1 tegument protein VP22 interacts with TAR proteins and inhibits nucleosome assembly but not regulation of histone acetylation by INHAT
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DOI：
10.1099/vir.0.19326-0
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发表时间：
2003-09-01
影响因子：
3.8
通讯作者：
O'Hare, P
中科院分区：
文献类型：
--
作者：
van Leeuwen, H;Okuwaki, M;O'Hare, P
亲和层析用于鉴定与单纯疱疹病毒（HSV）被膜蛋白VP 22相互作用的细胞蛋白。在一小组特异性结合VP 22的蛋白质中，我们鉴定了TAF-I（模板激活因子I），这是一种染色质重塑蛋白，与组蛋白伴侣蛋白NAP-1同源。TAF-I先前已显示通过与组蛋白的直接相互作用促进组蛋白更有序地转移到裸DNA。TAF-I作为INHAT（乙酰转移酶抑制剂）蛋白复合物的亚基，也与组蛋白结合，并掩盖组蛋白成为乙酰转移酶p300和PCAF的底物。使用体外试验的TAF-I活性在染色质组装，我们表明，VP 22抑制核小体沉积在DNA上结合TAF-I。我们还观察到VP 22与DNA非特异性结合，这种活性被TAF-I消除。然而，VP 22的存在并不影响INHAT在体外抑制p300或PCAF的组蛋白乙酰转移酶活性的性质。我们推测这种相互作用可能与感染早期的HSV DNA组织有关，例如，通过干扰基因组上的核小体沉积。与这种可能性相一致的是观察到转染细胞中TAF-I的过表达干扰HSV-1感染的进展。
Affinity chromatography was used to identify cellular proteins that interact with the herpes simplex virus (HSV) tegument protein VP22. Among a small set of proteins that bind specifically to VP22, we identified TAF-I (template-activating factor I), a chromatin remodelling protein and close homologue of the histone chaperone protein NAP-1. TAF-I has been shown previously to promote more ordered transfer of histones to naked DNA through a direct interaction with histones. TAF-I, as a subunit of the INHAT (inhibitor of acetyltransferases) protein complex, also binds to histones and masks them from being substrates for the acetyltransferases p300 and PCAF. Using in vitro assays for TAF-I activity in chromatin assembly, we show that VP22 inhibits nucleosome deposition on DNA by binding to TAF-I. We also observed that VP22 binds non-specifically to DNA, an activity that is abolished by TAF-I. However, the presence of VP22 does not affect the property of INHAT in inhibiting the histone acetyltransferase activity of p300 or PCAF in vitro. We speculate that this interaction could be relevant to HSV DNA organization early in infection, for example, by interfering with nucleosomal deposition on the genome. Consistent with this possibility was the observation that overexpression of TAF-I in transfected cells interferes with the progression of HSV-1 infection.