Signal cell seqencing of primary HCMV infections

人巨细胞病毒(HCMV)是一种常见于人类的疱疹病毒。人巨细胞病毒感染是终生的，通常不会对宿主造成明显的负担。在患有自然或获得性免疫缺陷的人中，巨细胞病毒可能是疾病甚至死亡的重要原因。巨细胞病毒也是导致出生缺陷的主要感染原因。病毒如何感染新宿主(原发感染)尚不清楚，尤其是在哺乳期间发生的传播中。在全球范围内代表大多数妇女的HCMV呈阳性的哺乳期妇女会在母乳中传播病毒。大约十分之四的感染巨细胞病毒的妇女会将病毒传播给她们的哺乳婴儿。这种传播是如何发生的，以及口腔中被感染的细胞的身份如何，目前还知之甚少。在这里，我们采用尖端的单细胞RNA测序技术来识别哺乳婴儿口腔中哪些细胞被感染，并在单个细胞的基础上确定这种感染的后果。这种方法允许我们提出一个假设，即在影响复制和宿主先天性反应的口腔原发感染过程中，HCMV优先感染上皮细胞亚群。我们将在两个目标上检验这一假设。第一，将单细胞RNA测序技术应用于HCMV感染的3D口腔上皮组织培养。第二个目标是将这项技术应用于分析哺乳婴儿口腔内的原发感染。这些新颖的研究将为人类巨细胞病毒原发感染提供新的知识，并为预防巨细胞病毒传播的改进干预措施的发展提供信息。

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.