Signal cell seqencing of primary HCMV infections

点击翻译按钮获取中文摘要

Human cytomegalovirus (HCMV) is a herpesvirus commonly found in humans. HCMV infections are lifelong and usually do not have an apparent burden on the host. In individuals with natural or acquired immunodeficiency, HCMV can be a significant cause of disease and even death. HCMV is also the leading infectious cause of birth defects. How the virus infects a new host (primary infection) is poorly understood, especially in transmissions that occur during nursing. Lactating women who are positive for HCMV—which, globally, represents most women—shed virus in breast milk. About 4 in 10 women with HCMV will transmit the virus to their nursing infant. How this transmission occurs and the identity of cells in the oral cavity that become infected are poorly understood. Here we adapt cutting edge single cell RNA sequencing technology to identify which cells are infected in the oral cavity of nursing infants and determine the consequences of this infection on an individual cell basis. This approach allows us to propose a hypothesis that HCMV preferentially infects subsets of epithelial cells during oral primary infections that impact replication and host innate responses. We will test this hypothesis across two aims. The first, will adapt the single cell RNA sequencing technology to HCMV infected cultures of 3D oral epithelia tissues. The second aim will apply the technology to analyze primary infections in the oral cavity of nursing infants. These novel studies will provide new knowledge into HCMV primary infections and inform the development of improved interventions that prevent HCMV transmission.