Endothelial cell-mediated uptake of a hepatitis B virus: A new concept of liver targeting of hepatotropic microorganisms
Endothelial cell-mediated uptake of a hepatitis B virus: A new concept of liver targeting of hepatotropic microorganisms
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DOI：
10.1053/jhep.2001.27810
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发表时间：
2001-10-01
期刊：
影响因子：
13.5
通讯作者：
Knolle, PA
中科院分区：
文献类型：
--
作者：
Breiner, KM;Schaller, H;Knolle, PA
肝脏是许多传染性病原体的目标，最明显的是肝炎病毒。然而，迄今为止发现的几种肝炎病毒受体分子普遍表达，因此不能解释有效的肝脏靶向。利用模型乙型肝炎病毒鸭乙型肝炎病毒（DHBV），我们获得的数据表明，清除肝窦内皮细胞（LSEC），而不是肝细胞本身，在病毒病原体进入肝脏的初始摄取中起关键作用。荧光病毒颗粒和包被金颗粒在实验动物以及原代肝细胞培养中的实验表明，病毒底物优先被LSEC吸收。在细胞内，LSEC内化的荧光病毒颗粒与DHBV受体羧基肽酶D共定位，表明受体介导的对溶酶体降解的拯救。为了符合乙型肝炎病毒在体内感染肝细胞的高效率，我们提出最初被LSEC清除的病毒随后被释放到感染邻近的肝细胞，这是唯一能够复制这些病毒的细胞。这种原发性摄取到LSEC的模型可能说明了血源性促肝药物靶向肝脏中肝细胞的一般机制。
The liver is a target for many infectious agents, most notably hepatitis viruses. However, several receptor molecules identified so far for hepatitis viruses were found to be ubiquitously expressed and can thus not account for efficient liver targeting. Using a model hepatitis B virus, the duck hepatitis B virus (DHBV), we have obtained data indicating that scavenging liver sinusoidal endothelial cells (LSEC), rather than hepatocytes themselves, play the key role in the initial uptake of viral pathogens into the liver. Experiments with fluorescent viral particles and coated gold particles in test animals, as well as in primary liver cell culture, demonstrated a preferential uptake of the viral substrates into LSEC. Intracellularly, fluorescent virus particles internalized by LSEC colocalized with the DHBV receptor, carboxypeptidase D, suggesting receptor-mediated rescue from lysosomal degradation. To comply with the high efficiency by which hepatitis B viruses infect hepatocytes in vivo, we propose that viruses initially scavenged by LSEC are thereafter released to infect adjacent hepatocytes, the only cells capable of replicating these viruses. Such a model of primary uptake into LSEC may illustrate a general mechanism by which blood-borne hepatotropic agents are targeted to the hepatocytes in the liver.