麻疹病毒疫苗减毒：淋巴组织的次优感染及嗜性改变

Measles virus vaccine attenuation: suboptimal infection of lymphatic tissue and tropism alteration.

作者信息

Condack Cristian, Grivel Jean-Charles, Devaux Patricia, Margolis Leonid, Cattaneo Roberto

机构信息

Laboratory of Molecular and Cellular Biophysics, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.

出版信息

J Infect Dis. 2007 Aug 15;196(4):541-9. doi: 10.1086/519689. Epub 2007 Jun 29.

DOI:10.1086/519689

PMID:17624839

Abstract

The mechanisms of measles virus (MV) vaccine attenuation are insufficiently characterized. Because the Edmonston vaccine strain can enter cells through CD46 in addition to the primary MV receptor signaling lymphocyte activation molecule (SLAM or CD150), we asked whether and how its tropism is altered. In human tonsillar tissue, this vaccine strain infects naive (CD45RA(+)CD62L(+)) T lymphocytes, which express SLAM very infrequently, with much higher efficiency than do wild-type strains. By contrast, it infects B lymphocytes, macrophages, and NK cells with significantly lower efficiencies than those of wild-type strains. Infection levels by wild-type strains correlate with the frequency of SLAM expression and are highest in B cells, which are 40%-55% infected. SLAM-expressing T cells are more readily infected by all MV strains than are SLAM-expressing B cells. Thus, vaccine attenuation may be caused by tropism alteration in combination with suboptimal replication.

摘要

麻疹病毒（MV）疫苗减毒的机制尚未得到充分阐明。由于埃德蒙斯顿疫苗株除了能通过主要的MV受体信号淋巴细胞激活分子（SLAM或CD150）进入细胞外，还能通过CD46进入细胞，因此我们探究了其嗜性是否以及如何发生改变。在人类扁桃体组织中，该疫苗株感染初始（CD45RA(+)CD62L(+)）T淋巴细胞的效率远高于野生型毒株，而这些初始T淋巴细胞极少表达SLAM。相比之下，它感染B淋巴细胞、巨噬细胞和NK细胞的效率则显著低于野生型毒株。野生型毒株的感染水平与SLAM表达频率相关，在B细胞中的感染水平最高，B细胞的感染率为40%-55%。表达SLAM的T细胞比表达SLAM的B细胞更容易被所有MV毒株感染。因此，疫苗减毒可能是由嗜性改变与次优复制共同导致的。