SMALL NUCLEAR RNAS ENCODED BY HERPESVIRUS SAIMIRI

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。Sm类的七个小核RNA由疱疹病毒Saimiri(HVS)编码，HVS是一种伽马疱疹病毒，可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，并在体外有效地转化T细胞。疱疹病毒Simiri U RNAs(HSURs)是人类免疫缺陷病毒潜伏感染T细胞中含量最丰富的病毒转录本，但不是病毒在体外复制或转化所必需的。我们比较了缺乏高度保守的HSURs的野生型和突变型HURS转化的绒猴T细胞，HSR1和2。微阵列和Northern分析表明，HSUR1和2的表达与少量宿主mRNAs的显著增加有关，包括T细胞受体β和伽马链，T细胞和自然杀伤(NK)细胞表面受体CD52和DAP10，以及与T细胞和NK细胞激活相关的细胞内蛋白-SKAP55、颗粒溶素和NKG7。用携带HSURs 1和2的慢病毒载体转导缺失突变的HVS转化的细胞后，其中三个转录本的上调被挽救。这些变化表明HSURs在调节一组显著定义的和生理上相关的宿主靶标方面发挥了意想不到的作用，这些宿主靶标参与了病毒转化的T细胞在潜伏期的激活。

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.