A single amino acid change in the hemagglutinin protein of measles virus determines its ability to bind CD46 and reveals another receptor on marmoset B cells
A single amino acid change in the hemagglutinin protein of measles virus determines its ability to bind CD46 and reveals another receptor on marmoset B cells
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DOI：
10.1128/jvi.72.4.2905-2916.1998
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发表时间：
1998-04-01
影响因子：
5.4
通讯作者：
Richardson, CD
中科院分区：
文献类型：
--
作者：
Hsu, EC;Sarangi, F;Richardson, CD
本文提供了在转化的绒猴和人B细胞上存在CD46以外的麻疹病毒受体的证据。我们首先发现，大多数绒猴组织缺少CD46的SCR1结构域，CD46是与埃德蒙斯顿麻疹病毒结合所必需的，埃德蒙斯顿麻疹病毒是一种实验室毒株，已在Vero猴子肾脏细胞中繁殖。尽管有这一缺失，但普通的绒猴被证明对麻疹病毒野生型分离株的感染很敏感，尽管它们不支持埃德蒙斯顿麻疹病毒的产生。正如人们从这些结果中预期的那样，麻疹病毒不能在猫头鹰猴子或猴肾细胞系中繁殖，但令人惊讶的是，麻疹病毒的野生型分离株(Montefiore 89)和埃德蒙斯顿实验室株都在B95-8绒猴B细胞上有效地生长。此外，针对CD46的抗体对绒猴B细胞的野生型感染没有影响，只部分抑制了埃德蒙斯顿实验室菌株在相同细胞中的复制。用表达埃德蒙斯顿株或Montefiore 89株麻疹病毒血凝素(H)蛋白的昆虫细胞直接结合试验来探测这些B细胞上的受体。表达Edmonston H但不表达野生型H的昆虫细胞与啮齿动物细胞结合，表面有CD46。另一方面，Montefiore 89H和Edmonston H蛋白均能与绒猴和人B细胞结合。大多数野生型H蛋白在第481位有天冬酰胺残基，可以通过用酪氨酸替换残基来转化为CD46结合表型。同样，埃德蒙斯顿H蛋白在其Tyr481转化为天冬酰胺时不与CD46结合。然而，该突变并不影响Edmonston H与绒猴和人类B细胞的结合能力。通过使用直接结合试验，上述结果提供了证据，证明灵长类B细胞上存在麻疹病毒的第二受体。
This paper provides evidence for a measles virus receptor other than CD46 on transformed marmoset and human B cells. We first showed that most tissues of marmosets are missing the SCR1 domain of CD46, which is essential for the binding of Edmonston measles virus, a laboratory strain that has been propagated in Vero monkey kidney cells. In spite of this deletion, the common marmoset was shown to be susceptible to infections by wild-type isolates of measles virus, although they did not support Edmonston measles virus production. As one would expect from these results, measles virus could not be propagated in owl monkey or marmoset kidney cell lines, but surprisingly, both a wild-type isolate (Montefiore 89) and the Edmonston laboratory strain of measles virus grew efficiently in B95-8 marmoset B cells. In addition, antibodies directed against CD46 had no effect on wild-type infections of marmoset B cells and only partially inhibited the replication of the Edmonston laboratory strain in the same cells. A direct binding assay with insect cells expressing the hemagglutinin (H) proteins of either the Edmonston or Montefiore 89 measles virus strains was used to probe the receptors on these B cells. Insect cells expressing Edmonston H but not the wild-type H bound to rodent cells with CD46 on their surface. On the other hand, both the Montefiore 89 H and Edmonston H proteins adhered to marmoset and human B cells. Most wild-type H proteins have asparagine residues at position 481 and can be converted to a CD46-binding phenotype by replacement of the residue with tyrosine. Similarly, the Edmonston H protein did not bind CD46 when its Tyr481 was converted to asparagine. However, this mutation did not affect the ability of Edmonston H to bind marmoset and human B cells. The preceding results provide evidence, through the use of a direct binding assay, that a second receptor for measles virus is present on primate B cells.