Dorner Marcus, Zucol Franziska, Alessi Davide, Haerle Stephan K, Bossart Walter, Weber Markus, Byland Rahel, Bernasconi Michele, Berger Christoph, Tugizov Sharof, Speck Roberto F, Nadal David
Experimental Infectious Diseases and Cancer Research, University Children's Hospital of Zurich, University of Zurich, Zurich, Switzerland.
J Virol. 2010 Jul;84(13):6667-77. doi: 10.1128/JVI.02675-09. Epub 2010 Apr 28.
Epstein-Barr virus (EBV) uses nasal mucosa-associated lymphoid tissue (NALT) as a portal of entry to establish life-long persistence in memory B cells. We previously showed that naïve and memory B cells from NALT are equally susceptible to EBV infection. Here we show that memory B cells from NALT are significantly more susceptible to EBV infection than those from remote lymphatic organs. We identify beta(1) integrin, which is expressed the most by naïve B cells of distinct lymphoid origin and by memory B cells from NALT, as a mediator of increased susceptibility to infection by EBV. Furthermore, we show that BMRF-2-beta(1) integrin interaction and the downstream signal transduction pathway are critical for postbinding events. An increase of beta(1) integrin expression in peripheral blood memory B cells provoked by CD40 stimulation plus B-cell receptor cross-linking increased the susceptibility of non-NALT memory B cells to EBV infection. Thus, EBV seems to utilize the increased activation status of memory B cells residing in the NALT to establish and ensure persistence.
爱泼斯坦-巴尔病毒（EBV）利用鼻黏膜相关淋巴组织（NALT）作为进入门户，在记忆B细胞中建立终身持续性感染。我们之前表明，来自NALT的幼稚B细胞和记忆B细胞对EBV感染同样敏感。在此我们表明，来自NALT的记忆B细胞比来自远端淋巴器官的记忆B细胞对EBV感染的敏感性显著更高。我们鉴定出β(1)整合素，其在不同淋巴来源的幼稚B细胞以及来自NALT的记忆B细胞中表达量最高，是EBV感染易感性增加的介导因子。此外，我们表明BMRF-2-β(1)整合素相互作用及下游信号转导通路对结合后事件至关重要。CD40刺激加B细胞受体交联引发的外周血记忆B细胞中β(1)整合素表达增加，提高了非NALT记忆B细胞对EBV感染的易感性。因此，EBV似乎利用驻留在NALT中的记忆B细胞增加的激活状态来建立并确保持续性感染。
