SMALL NUCLEAR RNAS ENCODED BY HERPESVIRUS SAIMIRI

疱疹病毒 SAIMIRI 编码的小核 RNA

• 批准号: 7349566
• 负责人: JOAN A. STEITZ
• 金额: $ 5.59万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7349566
• 关键词: SMALL; NUCLEAR; RNAS; ENCODED; HERPESVIRUS

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.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。 Sm 类的 7 个核小 RNA 由 Saimiri 疱疹病毒 (HVS) 编码，HVS 是一种 γ 疱疹病毒，可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，并在体外有效转化 T 细胞。疱疹病毒 saimiri U RNA (HSUR) 是 HVS 转化的潜伏感染 T 细胞中最丰富的病毒转录本，但不是病毒体外复制或转化所必需的。我们比较了用野生型或缺乏高度保守的 HSUR、HSUR 1 和 2 的突变型 HVS 转化的狨猴 T 细胞。微阵列和 Northern 分析表明，HSUR 1 和 2 表达与少量宿主 mRNA 的显着增加相关，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 CD52 和 DAP10 以及细胞内SKAP55、颗粒溶素和 NKG7 等蛋白质与 T 细胞和 NK 细胞激活相关。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，其中三个转录物的上调得以恢复。这些变化表明 HSUR 在调节一组明确且生理相关的宿主靶标方面发挥着意想不到的作用参与潜伏期病毒转化 T 细胞的激活。