The Immunological Consequences of Mouse Cytomegalovirus on Adipose Tissue

摘要 长期以来，脂肪组织一直被认为只是脂肪合成和能量储存的场所。然而，它已经 越来越清楚的是，脂肪组织的炎症状态对宿主免疫有深远的影响 和新陈代谢。最近的报告表明，病毒和寄生虫都能够直接 感染脂肪细胞和脂肪组织的细胞成分。此外，人类免疫缺陷 病毒(HIV)能够潜伏在脂肪中发现的T细胞中。巨细胞病毒(CMV)是一种普遍存在的 贝塔疱疹病毒会导致终生持续感染，巨细胞病毒研究的圣杯一直是 确定潜伏期的位置，但没有研究表明脂肪组织被感染或 有潜伏的和持久的病毒。CMV具有广泛的细胞和组织嗜性，敏感细胞均为 在脂肪组织中的表现。因此，有必要调查CMV的后果(如果有的话)。 脂肪内感染。为了了解巨细胞病毒感染对脂肪的影响(S)，我们将 采用C57BL/6小鼠巨细胞病毒(MCMV)感染模型。这项建议的目标是了解 巨细胞病毒在脂肪组织内传播的功能后果和机制。整体而言 这一提议的假设是MCMV传播到脂肪组织，复制，建立潜伏期， 导致终生的CD8 T细胞反应。我们将解决这一假设并实现这一目标 建议首先，通过qPCR确定感染过程中脂肪组织内感染的细胞类型(S)， 空斑分析和流式细胞术。我们还将确定MCMV是否能够从 在脂肪组织内。第二，我们将确定MCMV特异性CD8的动力学扩张和收缩 T细胞。研究脂肪组织在免疫反应中的感染和作用是一种新的和 因此，这项工作完成后，将代表着我们在根本上的重大进步 关于MCMV细胞趋向性和持久性的知识基础。这项提案的调查结果将要求 在感染的背景下考虑脂肪组织，这对疫苗学具有深远的影响， 免疫学、病毒学和内分泌学。

Abstract Adipose tissue has long been thought to simply be a site of lipid synthesis and energy storage. However, it has become increasingly clear that the inflammatory state of adipose tissue has profound effects on host immunity and metabolism. Recent reports have demonstrated that both viruses and parasites are capable of directly infecting the adipocytes and cellular constituents of adipose tissue. Furthermore, Human Immunodeficiency Virus (HIV) is capable of becoming latent within T cells found in adipose. Cytomegalovirus (CMV), a ubiquitous betaherpesvirus, results in a persistent lifelong infection and the holy grail of CMV research has been to identify sites of latency, but no study has demonstrated the extent to which adipose tissue is infected or harbors latent and persistent virus. CMV has a broad cellular and tissue tropism, and susceptible cells are all represented within the adipose tissue. Thus, it is necessary to investigate the consequences, if any, of CMV infection within adipose. In order to understand the consequence(s) of CMV infection on adipose we will employ the C57BL/6 mouse CMV (mCMV) model of infection. The goal of this proposal is to understand the functional consequences and mechanism of spread during mCMV infection within adipose tissue. The overall hypothesis of this proposal is that mCMV disseminates to adipose tissue, replicates, establishes latency, leading to an lifelong CD8 T cell response. We will address the hypothesis and achieve the goals of this proposal by first, determining the cell type(s) that are infected within adipose tissue during infection by qPCR, plaque assay, and flow cytometry. We will also determine if mCMV is capable of becoming reactivated from within adipose tissue. Second, we will determine the kinetic expansion and contraction of mCMV specific CD8 T cells. Investigation into infection of and the role of adipose tissue during an immune response is a new and growing field, thus this work, when completed, will represent a significant advancement in our fundamental base of knowledge regarding mCMV cell tropism and persistence. The findings of this proposal will call for the consideration of adipose tissue in the context of infection, which has far reaching impact on vaccinology, immunology, virology, and endocrinology.