Scavenger Receptor A: A New Route for Adenovirus 5
Scavenger Receptor A: A New Route for Adenovirus 5
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DOI：
10.1021/mp8000974
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发表时间：
2009-03-01
影响因子：
4.9
通讯作者：
Bellu, Anna Rita
中科院分区：
文献类型：
--
作者：
Haisma, Hidde J.;Boesjes, Marije;Bellu, Anna Rita
腺病毒是与呼吸道疾病、胃肠道疾病和/或结膜炎相关的常见病原体。目前，这种病毒被用作基因治疗试验的载体。病毒基因治疗应用的前景大大减少，因为病毒在全身给药后被肝巨噬细胞清除。腺病毒对巨噬细胞的嗜性和在巨噬细胞中的降解的机制知之甚少。我们发现了一种新的腺病毒受体，清道夫受体A（SR-A），负责在巨噬细胞中摄取病毒。与野生型细胞相比，表达SR-A的CHO细胞显示病毒转基因表达增加。用SR-A配体预孵育J774巨噬细胞显著降低腺病毒摄取。感染的J774细胞的电子显微镜分析显示病毒降解途径的激活。当SR-A被阻断时，用腺病毒感染小鼠导致肝巨噬细胞中病毒的大量减少。我们的数据为了解腺病毒在体内外巨噬细胞中的摄取和降解机制提供了基础。腺病毒SR-A摄取的抑制可用于基因治疗应用以提高其效率和功效。
Adenoviruses are common pathogens associated with respiratory diseases, gastrointestinal illnesses and/or conjunctivitis. Currently, this virus is used as a vector in gene therapy trials. The promise of viral gene therapy applications is substantially reduced because the virus is cleared by liver macrophages upon systemic administration. The mechanism underlying adenoviral tropism to and degradation in macrophages is poorly understood. We identified a new adenoviral receptor, the scavenger receptor A (SR-A), responsible for uptake of the virus in macrophages. CHO cells expressing SR-A showed increased viral transgene expression when compared with wild type cells. Preincubation of J774 macrophage cells with SR-A ligands decreased significantly adenoviral uptake. Electron-microscopy analysis of infected J774 cells showed activation of a viral degradation pathway. Infection of mice with adenovirus resulted in a substantial decrease of the virus in liver macrophages when SR-A was blocked. Our data provide a basis for understanding of the adenoviral uptake and degradation mechanism in macrophages in vitro and in vivo. Inhibition of adenoviral SR-A uptake can be utilized in gene therapy applications to increase its efficiency and efficacy.