The Immunological Consequences of Mouse Cytomegalovirus on Adipose Tissue

摘要

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.