SLAM (CD150)-independent measles virus entry as revealed by recombinant virus expressing green fluorescent protein
SLAM (CD150)-independent measles virus entry as revealed by recombinant virus expressing green fluorescent protein
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DOI：
10.1128/jvi.76.13.6743-6749.2002
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发表时间：
2002-07-01
影响因子：
5.4
通讯作者：
Yanagi, Y
中科院分区：
文献类型：
--
作者：
Hashimoto, K;Ono, N;Yanagi, Y
野生型麻疹病毒（MV）毒株使用人类信号淋巴细胞激活分子（SLAM）作为细胞受体，而埃德蒙斯顿毒株等疫苗毒株可以同时使用SLAM和CD46作为受体。尽管 SLAM 的表达仅限于免疫系统细胞（淋巴细胞、树突状细胞和单核细胞），但对人类和实验感染猴子的组织病理学研究表明，MV 也会感染 SLAM 阴性细胞，包括上皮细胞、内皮细胞和神经元细胞。为了解释这些发现，我们基于野生型 IC-B 菌株生产了表达增强型绿色荧光蛋白 (EGFP) 的重组 MV (IC323-EGFP)。 IC323-EGFP 显示出与亲本重组 MV 几乎相同的生长动力学，并产生在 SLAM 阳性细胞中表现出绿色自发荧光的大合胞体。有趣的是，所有检查的 SLAM 阴性细胞系在感染 IC323-EGFP 后也显示出绿色自发荧光，尽管病毒很难从最初感染的单个细胞中传播，因此不会诱导合胞体。以感染后表达EGFP的细胞数为指标，IC323-EGFP对SLAM阴性细胞的感染力比SLAM阳性细胞低2~3个log。抗MV血凝素抗体或融合阻断肽（但不是抗CD46抗体）阻断了SLAM阴性细胞的IC323-EGFP感染。这种感染发生在通过内吞作用进入被抑制的条件下。这些结果表明，W 通过使用除 SLAM 或 CD46 之外的尚未鉴定的受体，可以感染多种细胞，尽管效率较低，这部分解释了在体内观察到的 SLAM 阴性细胞的 MV 感染。
Wild-type measles virus (MV) strains use human signaling lymphocyte activation molecule (SLAM) as a cellular receptor, while vaccine strains such as the Edmonston strain can use both SLAM and CD46 as receptors. Although the expression of SLAM is restricted to cells of the immune system (lymphocytes, dendritic cells, and monocytes), histopathological studies with humans and experimentally infected monkeys have shown that MV also infects SLAM-negative cells, including epithelial, endothelial, and neuronal cells. In an attempt to explain these findings, we produced the enhanced green fluorescent protein (EGFP) -expressing recombinant MV (IC323-EGFP) based on the wild-type IC-B strain. IC323-EGFP showed almost the same growth kinetics as the parental recombinant MV and produced large syncytia exhibiting green autofluorescence in SLAM-positive cells. Interestingly, all SLAM-negative cell lines examined also showed green autofluorescence after infection with IC323-EGFP, although the virus hardly spread from the originally infected individual cells and thus did not induce syncytia. When the number of EGFP-expressing cells after infection was taken as an indicator, the infectivities of IC323-EGFP for SLAM-negative cells were 2 to 3 logs lower than those for SLAM-positive cells. Anti-MV hemagglutinin antibody or fusion block peptide, but not anti-CD46 antibody, blocked IC323-EGFP infection of SLAM-negative cells. This infection occurred under conditions in which entry via endocytosis was inhibited. These results indicate that W can infect a variety of cells, albeit with a low efficiency, by using an as yet unidentified receptor(s) other than SLAM or CD46, in part explaining the observed MV infection of SLAM-negative cells in vivo.