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γ疱疹病毒MHV68，类似于人γ疱疹病毒，感染并潜伏在B细胞中，并在感染动物中引起淋巴增生性疾病和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。Aim 1中提出的体外实验将验证mhv68驱动的脾细胞增殖是由于B细胞的增殖，并由分泌的有丝分裂原介导的假设。在特定目标中，2个MHV68突变体将用于确定MHV68基因产物，该产物在体外负责B细胞增殖。特异性目的3将使用MHV68淋巴瘤形成模型来验证B细胞体外增殖所需的MHV68蛋白也在MHV68诱导的体内淋巴瘤形成中发挥作用的假设。

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.