THE ASIALOGLYCOPROTEIN RECEPTOR IS A POTENTIAL LIVER-SPECIFIC RECEPTOR FOR MARBURG VIRUS

THE ASIALOGLYCOPROTEIN RECEPTOR IS A POTENTIAL LIVER-SPECIFIC RECEPTOR FOR MARBURG VIRUS
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DOI:
10.1099/0022-1317-76-2-393
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发表时间:
1995-02-01
影响因子:
3.8
通讯作者:
KLENK, HD
KLENK, HD
中科院分区:
医学3区
文献类型:
--
作者:
BECKER, S;SPIESS, M;KLENK, HD

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肝脏是马尔堡病毒(MBG)的主要靶器官之一,马尔堡病毒是一种引起严重出血热的丝状病毒,在人类和非人类灵长类动物中死亡率很高。在某些细胞中生长的MBG不含神经氨酸,但在其表面糖蛋白上具有末端半乳糖。这一观察结果表明,肝细胞的去唾液酸糖蛋白受体(ASGP-R)可能作为MBG在肝脏中的受体。结合研究表明,MBG与表达ASGP-R的HepG 2细胞的结合,但不与ASGP-R阴性E6 Vero细胞的结合,具有配体与ASGP-R结合的特征:结合依赖于钙,并被过量的脱唾液酸胎球蛋白和抗ASGP-R抗血清抑制。去唾液酸胎球蛋白和特异性抗血清也能抑制MBG感染HepG 2细胞。此外,还表明在NIH 3 T3细胞中表达ASGP-R cDNA使这些细胞对MBG感染的易感性增强4.5倍。因此,MBG与肝ASGP-R的相互作用可以解释该病毒明显的嗜肝性。
The liver is one of the main target organs of Marburg virus (MBG), a filovirus causing severe haemorrhagic fever with a high fatality rate in humans and non-human primates. MBG grown in certain cells does not contain neuraminic acid, but has terminal galactose on its surface glycoprotein. This observation indicated that the asialoglycoprotein receptor (ASGP-R) of hepatocytes may serve as a receptor for MBG in the liver. Binding studies revealed that the attachment of MBG to ASGP-R-expressing HepG2 cells, but not to ASGP-R-negative E6 Vero cells, has the characteristics of ligand binding to the ASGP-R: binding is dependent on calcium and is inhibited by excess asialofetuin and by anti-ASGP-R antiserum. Asialofetuin and the specific antiserum also inhibited MBG infection of HepG2 cells. In addition, it was shown that expression of ASGP-R cDNA in NIH 3T3 cells enhanced the susceptibility of these cells to MBG infection 4.5-fold. Interaction of MBG with the hepatic ASGP-R could thus explain the marked hepatotropism of the virus.