Inhibition of Epstein-Barr Virus Infection by Lactoferrin
Inhibition of Epstein-Barr Virus Infection by Lactoferrin
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乳铁蛋白对 Epstein-Barr 病毒感染的抑制
DOI：
10.1159/000336178
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发表时间：
2012-01-01
影响因子：
5.3
通讯作者：
Li, Guiyuan
中科院分区：
文献类型：
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作者：
Zheng, Ying;Zhang, Wenling;Li, Guiyuan
乳铁蛋白 (LF) 是一种多功能糖蛋白，在抵抗感染的天然免疫防御中发挥重要作用，包括人类疱疹病毒，如巨细胞病毒和单纯疱疹病毒 1 型和 2 型。然而，其抗 Epstein-Barr 病毒（EBV，一种 γ-疱疹病毒）功能尚未在文献中报道。 EBV 在所有人群中广泛存在，并且被认为与肿瘤发生有关，例如淋巴瘤和鼻咽癌 (NPC)。我们之前报道过 LF 在 NPC 组织中表达水平显着较低，并且可能是一种肿瘤抑制因子。由于EBV感染是鼻咽癌发展的主要致癌物，我们研究了LF对EBV感染的影响，发现LF可以保护人原代B淋巴细胞和鼻咽上皮细胞免受EBV感染，但对EBV基因组DNA复制没有影响。 LF 通过直接结合 B 细胞表面的 EBV 受体 (CD21) 来阻止原代 B 细胞的 EBV 感染。组织阵列免疫组织化学显示，NPC 标本中 LF 表达显着下调，其中观察到高 EBV 病毒衣壳抗原 IgA 水平。这些数据表明 LF 可能抑制 EBV 感染，并且其下调可能有助于 NPC 的发展。
Lactoferrin (LF) is a multifunctional glycoprotein that plays an important role in native immune defense against infections, including human herpetic viruses, such as cytomegalovirus and herpes simplex virus types 1 and 2. However, its anti-Epstein-Barr virus (EBV, a γ-herpesvirus) function has not been reported in the literature. EBV is widespread in all human populations and is believed to be linked to tumorigenesis, such as lymphomas and nasopharyngeal carcinoma (NPC). We previously reported that LF expressed a significantly lower level in NPC tissues and was a likely tumor suppressor. Since EBV infection is a major carcinogen of NPC development, we investigated the effect of LF on EBV infection and found that LF could protect human primary B lymphocytes and nasopharyngeal epithelial cells from EBV infection, but had no effect on EBV genome DNA replication. LF prevented EBV infection of primary B cells mediated by its direct binding to the EBV receptor (CD21) on the B-cell surface. Tissue array immunohistochemistry revealed that LF expression was significantly downregulated in NPC specimens, in which high EBV viral capsid antigen-IgA levels were observed. These data suggest that LF may inhibit EBV infection and that its downregulation could contribute to NPC development.