Regulation of gHV68-induced B cell proliferation

gHV68 诱导的 B 细胞增殖的调节

• 批准号: 6936276
• 负责人: Vera L. Tarakanova
• 金额: $ 1.57万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6936276
• 关键词: B lymphocyte; Gammaherpesvirinae; laboratory mouse; lymphocyte proliferation; postdoctoral investigator

DESCRIPTION (provided by applicant): Uncontrolled proliferation is a hallmark of malignant lesions, including B cell lymphomas. Murine gammaherpesvirus MHV68, similar to human gammaherpesviruses, infects and remains latent in B cells and causes lymphoproliferative disorders and B cell lymphomas in infected animals. MHV68 induces proliferation of murine splenocytes and activation of B cells. The mechanisms of MHV68-induced cellular proliferation are not clear. The connection between MHV68-induced proliferation and lymphomagenesis has not been examined, but is likely to exist. Proposed studies focus on the understanding of viral and host factors involved in MHV68-driven B cell proliferation. In vitro experiments proposed in Aim 1 will test the hypothesis that MHV68-driven splenocyte proliferation is due to proliferation of B cells and is mediated by a secreted mitogen. In specific aim 2 MHV68 mutants will be used to determine a MHV68 gene product(s) that is responsible for B cell proliferation in vitro. A model of MHV68 lymphomagenesis will be used in Specific Aim 3 to test the hypothesis that MHV68 protein(s) required for B cell proliferation in vitro also play a role in MHV68-induced lymphomagenesis in vivo.

描述（由申请方提供）：不受控制的增殖是恶性病变的标志，包括B细胞淋巴瘤。 鼠γ疱疹病毒MHV 68类似于人γ疱疹病毒，感染并潜伏在B细胞中，并在感染的动物中引起淋巴增生性疾病和B细胞淋巴瘤。 MHV 68诱导鼠脾细胞增殖和B细胞活化。 MHV 68诱导细胞增殖的机制尚不清楚。MHV 68诱导的增殖和淋巴瘤发生之间的联系尚未研究，但可能存在。 建议的研究集中在了解病毒和宿主因素参与MHV 68驱动的B细胞增殖。 目的1中提出的体外实验将检验MHV 68驱动的脾细胞增殖是由于B细胞增殖并由分泌的有丝分裂原介导的假设。 具体而言，将使用2种MHV 68突变体来确定负责体外B细胞增殖的MHV 68基因产物。 特定目标3将使用MHV 68淋巴瘤发生模型来检验以下假设：体外B细胞增殖所需的MHV 68蛋白也在体内MHV 68诱导的淋巴瘤发生中发挥作用。