SMALL NUCLEAR RNAS ENCODED BY HERPESVIRUS SAIMIRI

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。Sm类的七种小核RNA由松鼠猴疱疹病毒（HVS）编码，所述松鼠猴疱疹病毒是一种γ疱疹病毒，其在新世界灵长类动物中引起侵袭性T细胞白血病和淋巴瘤，并在体外有效地转化T细胞。疱疹病毒松鼠猴U RNA（HSUR）是HVS转化的潜伏感染的T细胞中最丰富的病毒转录物，但不是体外病毒复制或转化所必需的。我们比较了用野生型或缺乏最高度保守的HSUR（HSUR 1和2）的突变型HVS转化的绒猴T细胞。微阵列和北方分析显示，HSUR 1和2的表达与少量宿主mRNA的显著增加相关，包括T细胞受体β和γ链、T细胞和自然杀伤（NK）细胞表面受体CD 52和DAP 10以及与T细胞和NK细胞活化相关的细胞内蛋白-SKAP 55、颗粒溶解素和NKG 7。在用携带HSUR 1和2的慢病毒载体转导缺失突变型HVS转化细胞后，这些转录物中的三种的上调被拯救。这些变化表明HSUR在调节一组显著定义和生理相关的宿主靶标中具有意想不到的作用，这些靶标参与潜伏期期间病毒转化T细胞的活化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Seven small nuclear RNAs of the Sm class are encoded by Herpesvirus saimiri (HVS), a gamma Herpesvirus that causes aggressive T cell leukemias and lymphomas in New World primates and efficiently transforms T cells in vitro. The Herpesvirus saimiri U RNAs (HSURs) are the most abundant viral transcripts in HVS-transformed, latently infected T cells but are not required for viral replication or transformation in vitro. We have compared marmoset T cells transformed with wild-type or a mutant HVS lacking the most highly conserved HSURs, HSURs 1 and 2. Microarray and Northern analyses reveal that HSUR 1 and 2 expression correlates with significant increases in a small number of host mRNAs, including the T cell-receptor beta and gamma chains, the T cell and natural killer (NK) cell-surface receptors CD52 and DAP10, and intracellular proteins--SKAP55, granulysin, and NKG7--linked to T cell and NK cell activation. Upregulation of three of these transcripts was rescued after transduction of deletion-mutant-HVS-transformed cells with a lentiviral vector carrying HSURs 1 and 2. These changes indicate an unexpected role for the HSURs in regulating a remarkably defined and physiologically relevant set of host targets involved in the activation of virally transformed T cells during latency.