SMALL NUCLEAR RNAS ENCODED BY HERPESVIRUS SAIMIRI

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。Sm类的7个小核rna是由猴疱疹病毒（HVS）编码的，猴疱疹病毒是一种伽马疱疹病毒，在新大陆灵长类动物中引起侵袭性T细胞白血病和淋巴瘤，并在体外有效转化T细胞。猴疱疹病毒U rna （HSURs）在hvs转化的潜伏感染T细胞中是最丰富的病毒转录物，但在体外并不需要病毒复制或转化。我们比较了用野生型或突变型HVS转化的狨猴T细胞，这些HVS缺乏最高度保守的HSURs， HSURs 1和2。微阵列和Northern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链和γ链、T细胞和自然杀伤细胞（NK）表面受体CD52和DAP10，以及与T细胞和NK细胞活化相关的细胞内蛋白SKAP55、颗粒蛋白和NKG7。在用携带hrs 1和2的慢病毒载体转导缺失突变的hvs转化细胞后，其中三个转录本的上调得以恢复。这些变化表明，HSURs在调节潜伏期病毒转化T细胞激活过程中涉及的一组明确的、生理相关的宿主靶标方面具有意想不到的作用。

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.