ROLE OF GM IN KSHV ENTRY, EGRESS AND VIRUS-INDUCED CELL FUSION

GM 在 KSHV 进入、排出和病毒诱导的细胞融合中的作用

• 批准号: 7381334
• 负责人: OSWALD D'AUVERGNE
• 金额: $ 10.34万
• 依托单位: LOUISIANA STATE UNIV A&M COL BATON ROUGE
• 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/7381334
• 关键词: ROLE; GM; KSHV; ENTRY; EGRESS

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. Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8, belongs in the gammaherpesvirinae subfamily and is believed to be the etiologic agent of Kaposi's sarcoma, primary effusion lymphoma, and a subset of multicentric Castleman's disease. KSHV, similar to the other viruses in the herpesvirus family, specifies numerous glycoproteins which are expressed during the virus lifecycle. Many of these KSHV glycoproteins have been shown to be important in virus entry, egress and virus-induced cell fusion. Glycoprotein M (gM) and gN are known to play important roles in multiple steps of herpesviruses, while their potential roles in KSHV infections are unknown. The central hypothesis of this project is that the KSHV gM and gN serve essential roles in two critical facets of the viral lifecycle: a) cytoplasmic virion morphogenesis and egress; b) virus-induced cell fusion. The overall experimental approach of the proposed investigations is to generate KSHV recombinant viruses deficient in either glycoprotein M (gM) or glycoprotein N (gN) genes utilizing the KSHV genome cloned into a bacterial artificial chromosome (BAC). These viruses will be utilized to address the functions of these two glycoproteins in virion morphogenesis and egress, and virus-induced cell fusion caused by a KSHV mutant virus having syncytial mutations in gB. Specific Aim I: To construct and genetically characterize KSHV-BAC36 delta gM (gM-null) and BAC36 delta gN (gN-null) mutants utilizing the pGET-Rec recombination system in DH10B E. coli Specific Aim II: To assess the role of KSHV gM and gN in cytoplasmic virion morphogenesis and egress, and virus-induced cell fus

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。卡波西肉瘤相关疱疹病毒 (KSHV)，也称为人类疱疹病毒 8 型，属于伽马疱疹病毒亚科，被认为是卡波西肉瘤、原发性渗出性淋巴瘤和多中心卡斯尔曼病的一个亚型的病原体。 KSHV 与疱疹病毒家族中的其他病毒类似，指定了在病毒生命周期中表达的多种糖蛋白。许多 KSHV 糖蛋白已被证明在病毒进入、排出和病毒诱导的细胞融合中发挥重要作用。已知糖蛋白 M (gM) 和 gN 在疱疹病毒的多个步骤中发挥重要作用，但它们在 KSHV 感染中的潜在作用尚不清楚。该项目的中心假设是 KSHV gM 和 gN 在病毒生命周期的两个关键方面发挥着重要作用：a) 细胞质病毒颗粒形态发生和流出； b) 病毒诱导的细胞融合。所提出的研究的总体实验方法是利用克隆到细菌人工染色体（BAC）中的 KSHV 基因组来产生糖蛋白 M（gM）或糖蛋白 N（gN）基因缺陷的 KSHV 重组病毒。这些病毒将用于解决这两种糖蛋白在病毒粒子形态发生和排出中的功能，以及由在 gB 中具有合胞体突变的 KSHV 突变病毒引起的病毒诱导的细胞融合。 具体目标 I：利用 DH10B 大肠杆菌中的 pGET-Rec 重组系统构建 KSHV-BAC36 delta gM (gM-null) 和 BAC36 delta gN (gN-null) 突变体并进行遗传表征 具体目标 II：评估KSHV gM 和 gN 在细胞质病毒颗粒形态发生和排出以及病毒诱导的细胞融合中的作用