Adaptation of wild-type measles virus to CD46 receptor usage
Adaptation of wild-type measles virus to CD46 receptor usage
复制标题
DOI：
10.1007/s007050170169
复制
发表时间：
2001-01-01
影响因子：
2.7
通讯作者：
Bolt, G
中科院分区：
文献类型：
--
作者：
Nielsen, L;Blixenkrone-Moller, M;Bolt, G
麻疹病毒疫苗株以CD46为受体，下调感染细胞表面CD46的表达。在B淋巴细胞上分离和传代的MVS(野生型MVS)似乎使用另一种受体，并不下调CD46。在本研究中，我们发现在人或绒猴B淋巴细胞上分离MV并不改变相对于患者体内的MV血凝素(H)蛋白。野生型分离株分别适应于人上皮细胞系Hep-2和猴成纤维细胞系Vero。所有Hep-2细胞适应病毒和4个Vero细胞适应病毒中的1个获得了使用CD46作为受体的能力，这是通过它们感染表达人CD46的小鼠细胞的能力来衡量的。对CD46受体使用的适应与MVH蛋白的481位氨基酸从天冬氨酸替换为酪氨酸有关，但与CD46下调无关。本研究表明，野生型MV可以通过适应不表达野生型受体的细胞来诱导CD46受体的使用，并提示在目前MV疫苗株的祖病毒分离和减毒过程中，类似的机制作用于它们。
Vaccine strains of measles virus (MV) use CD46 as receptor and downregulate CD46 from the surface of infected cells. MVs isolated and passaged on B-lymphoid cells (wild-type MVs) seem to use another receptor and do not downregulate CD46. In the present study, we found that isolation of MV on human or marmoset B-lymphoid cells did not alter the MV haemagglutinin (H) protein relative to that in the patient. The wild-type isolates were adapted to the human epithelial HEp-2 cell line or the monkey fibroblast Vero cell line. All HEp-2 cell adapted viruses and 1 out of 4 Vero cell adapted viruses acquired the capacity to use CD46 as receptor, as measured by their ability to infect murine cells expressing human CD46. Adaptation to CD46 receptor usage was coupled to substitution of amino acid 481 of the MVH protein from asparagine to tyrosine but not to CD46 downregulation. The present study demonstrates that CD46 receptor usage can be induced by adaptation of wild-type MV to cells that do not express a wild-type receptor and suggests that a similar mechanism acted on the progenitor viruses of the present MV vaccine strains during their isolation and attenuation.