Regulation of gHV68-induced B cell proliferation

描述（由申请人提供）：不受控制的增殖是恶性病变的标志，包括 B 细胞淋巴瘤。 鼠伽马疱疹病毒 MHV68 与人类伽马疱疹病毒类似，可感染 B 细胞并潜伏在 B 细胞中，并在受感染的动物中引起淋巴增殖性疾病和 B 细胞淋巴瘤。 MHV68 诱导小鼠脾细胞增殖和 B 细胞活化。 MHV68诱导细胞增殖的机制尚不清楚。 MHV68 诱导的增殖和淋巴瘤发生之间的联系尚未得到检验，但很可能存在。 拟议的研究重点是了解参与 MHV68 驱动的 B 细胞增殖的病毒和宿主因素。 目标 1 中提出的体外实验将检验以下假设：MHV68 驱动的脾细胞增殖是由 B 细胞增殖引起的，并且由分泌的有丝分裂原介导。 具体目标是使用 2 个 MHV68 突变体来确定负责体外 B 细胞增殖的 MHV68 基因产物。 具体目标 3 将使用 MHV68 淋巴瘤发生模型来检验以下假设：体外 B 细胞增殖所需的 MHV68 蛋白也在 MHV68 诱导的体内淋巴瘤发生中发挥作用。

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.