Human receptor for measles virus (CD46) enhances nitric oxide production and restricts virus replication in mouse macrophages by modulating production of alpha/beta interferon
Human receptor for measles virus (CD46) enhances nitric oxide production and restricts virus replication in mouse macrophages by modulating production of alpha/beta interferon
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DOI：
10.1128/jvi.74.3.1252-1257.2000
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发表时间：
2000-02-01
影响因子：
5.4
通讯作者：
Wong, TC
中科院分区：
文献类型：
--
作者：
Katayama, Y;Hirano, A;Wong, TC
补体调节蛋白CD 46是麻疹病毒（MV）的人细胞受体。在这项研究中，我们研究了为什么小鼠巨噬细胞表达人CD 46限制MV复制和产生更高水平的一氧化氮（NO）在响应MV和γ干扰素（IFN-γ）。用抗IFN-α/β的抗体处理MV感染的表达CD 46的小鼠巨噬细胞阻断NO的产生。针对IFN-α/β的抗体还抑制MV对表达CD 46的小鼠巨噬细胞中IFN-γ诱导的KO产生的增强作用。这些抗体不影响单独由IFN-γ诱导的NO产生。这些数据表明MV通过IFN-α/β的作用增强表达CD 46的小鼠巨噬细胞中的NO产生。表达缺乏胞质结构域的人CD 46突变体的小鼠巨噬细胞对bnl高度敏感。这些细胞在感染MV时产生低得多的NO和IFN-α/β水平，表明CD 46胞质结构域增强IFN-α/β产生。当表达无尾人CD 46序列的小鼠巨噬细胞暴露于MV感染的表达完整人CD 46的小鼠巨噬细胞的培养基时，病毒蛋白合成和细胞病变效应的发展受到抑制。用针对IFN-alpha/beta的抗体预处理添加的培养基可以消除这些抗病毒作用。总而言之，这些发现表明小鼠巨噬细胞中人CD 46的表达增强了响应MV感染的IFN-alpha/beta的产生，并且IFN-alpha/beta与IFN-gamma协同作用，以增强NO的产生并限制病毒蛋白质合成和病毒复制。人CD 46在小鼠巨噬细胞中的这种新功能需要CD 46胞质结构域。
Complement regulatory protein CD46 is a human cell receptor for measles virus (MV). In this study, we investigated why mouse macrophages expressing human CD46 restricted MV replication and produced higher levels of nitric oxide (NO) in response to MV and gamma interferon (IFN-gamma). Treatment of MV-infected CD46-expressing mouse macrophages with antibodies against IFN-alpha/beta blocked NO production. Antibodies against IFN-alpha/beta also inhibited the augmenting effect of MV on IFN-gamma-induced KO production in CD46-expressing mouse macrophages. These antibodies did not affect NO production induced by IFN-gamma alone, These data suggest that MV enhances NO production in CD46-expressing mouse macrophages through action of IFN-alpha/beta. Mouse macrophages expressing a human CD46 mutant lacking the cytoplasmic domains were highly susceptible to bnl These cells produced much lower levels of NO and IFN-alpha/beta upon infection MV, suggesting the CD46 cytoplasmic domains enhanced IFN-alpha/beta production. When mouse macrophages expressing tailless human CD46 sere exposed to culture medium from MV-infected mouse macrophages expressing intact human CD46, viral protein synthesis and development of cytopathic effects were suppressed. Pretreating the added culture medium with antibodies against IFN-alpha/beta abrogated these antiviral effects, Taken together, these findings suggest that expression of human CD46 in mouse macrophages enhances production of IFN-alpha/beta in response to MV infection, and IFN-alpha/beta synergizes with IFN-gamma to enhance NO production and restrict viral protein synthesis and virus replication. This novel function of human CD46 in mouse macrophages requires the CD46 cytoplasmic domains.