Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
PLoS One. 2012;7(8):e43196. doi: 10.1371/journal.pone.0043196. Epub 2012 Aug 29.
Herpesviruses are characterized by their ability to establish lifelong latent infection. The gammaherpesvirus subfamily is distinguished by lymphotropism, establishing and maintaining latent infection predominantly in B lymphocytes. Consequently, gammaherpesvirus pathogenesis is closely linked to normal B cell physiology. Murine gammaherpesvirus 68 (MHV68) pathogenesis in laboratory mice has been extensively studied as a model system to gain insights into the nature of gammaherpesvirus infection in B cells and their associated lymphoid compartments. In addition to B cells, MHV68 infection of macrophages contributes significantly to the frequency of viral genome-positive cells in the peritoneal cavity throughout latency. The omentum, a sheet of richly-vascularized adipose tissue, resides in the peritoneal cavity and contains clusters of immune cell aggregates termed milky spots. Although the value of the omentum in surgical wound-healing has long been appreciated, the unique properties of this tissue and its contribution to both innate and adaptive immunity have only recently been recognized. To determine whether the omentum plays a role in gammaherpesvirus pathogenesis we examined this site during early MHV68 infection and long-term latency. Following intraperitoneal infection, immune aggregates within the omentum expanded in size and number and contained virus-infected cells. Notably, a germinal-center B cell population appeared in the omentum of infected animals with earlier kinetics and greater magnitude than that observed in the spleen. Furthermore, the omentum harbored a stable frequency of viral genome-positive cells through early and into long-term latency, while removal of the omentum prior to infection resulted in a slight decrease in the establishment of splenic latency following intraperitoneal infection. These data provide the first evidence that the omentum is a site of chronic MHV68 infection that may contribute to the maintenance of chronic infection.
疱疹病毒的特征是能够建立终身潜伏感染。γ疱疹病毒亚科的特点是具有淋巴趋向性，主要在 B 淋巴细胞中建立和维持潜伏感染。因此，γ疱疹病毒的发病机制与正常 B 细胞生理学密切相关。作为一种模型系统，实验室中小鼠的鼠γ疱疹病毒 68（MHV68）发病机制已被广泛研究，以深入了解 B 细胞中γ疱疹病毒感染的性质及其相关淋巴组织。除了 B 细胞，MHV68 感染巨噬细胞也显著增加了潜伏期间腹腔内病毒基因组阳性细胞的频率。大网膜是一层富含血管的脂肪组织，位于腹腔内，包含称为乳斑的免疫细胞聚集簇。尽管大网膜在手术伤口愈合中的价值早已被人们所认识，但直到最近才认识到这种组织的独特特性及其对固有和适应性免疫的贡献。为了确定大网膜是否在γ疱疹病毒发病机制中发挥作用，我们在早期 MHV68 感染和长期潜伏期间检查了该部位。腹腔内感染后，大网膜内的免疫聚集物体积和数量增加，并包含病毒感染的细胞。值得注意的是，感染动物的大网膜中出现了生发中心 B 细胞群体，其出现的动力学和幅度都比在脾脏中更早更大。此外，大网膜在早期和长期潜伏期间保持了稳定的病毒基因组阳性细胞频率，而在感染前切除大网膜会导致腹腔内感染后脾脏潜伏建立的频率略有降低。这些数据首次提供了证据表明大网膜是 MHV68 慢性感染的部位，可能有助于维持慢性感染。
