Incorporation of Host Complement Regulatory Proteins into Newcastle Disease Virus Enhances Complement Evasion
Incorporation of Host Complement Regulatory Proteins into Newcastle Disease Virus Enhances Complement Evasion
复制标题
DOI：
10.1128/jvi.00886-12
复制
发表时间：
2012-12-01
影响因子：
5.4
通讯作者：
Subbiah, Elankumaran
中科院分区：
文献类型：
--
作者：
Biswas, Moanaro;Johnson, John B.;Subbiah, Elankumaran
纽卡斯尔病病毒（NDV）是一种禽类副粘病毒，具有肿瘤选择性，目前被认为是一种临床溶瘤病毒和疫苗载体。在这项研究中，我们分析了补体对从鸡胚蛋中纯化的NDV的中和作用，鸡胚蛋是病毒生产的常见来源。新鲜正常人血清（NHS）通过多种补体激活途径中和NDV，不依赖于中和抗体。中和与C3沉积和C2、C3、C4和C5组分的活化相关。有趣的是，在哺乳动物细胞系中生长的NDV对NHS的补体中和具有抗性。为了证实将补体活性调节因子（RCA）掺入病毒包膜中是否提供补体抗性，我们在用CD46或HeLa细胞稳定转染的CHO细胞中培养NDV，所述CHO细胞或HeLa细胞强烈表达CD46和CD55。在RCA表达细胞中生长的NDV通过在病毒粒子上掺入CD46和CD55而对补体具有抗性。病毒体上的哺乳动物CD 46和CD 55分子表现出同源限制，因为缺乏NDV中和抗体的鸡血清能够有效地中和这些病毒体。将鸡RCA掺入含胚蛋中产生的NDV中同样提供了对鸡血清的种属特异性。
Newcastle disease virus (NDV), an avian paramyxovirus, is inherently tumor selective and is currently being considered as a clinical oncolytic virus and vaccine vector. In this study, we analyzed the effect of complement on the neutralization of NDV purified from embryonated chicken eggs, a common source for virus production. Fresh normal human serum (NHS) neutralized NDV by multiple pathways of complement activation, independent of neutralizing antibodies. Neutralization was associated with C3 deposition and the activation of C2, C3, C4, and C5 components. Interestingly, NDV grown in mammalian cell lines was resistant to complement neutralization by NHS. To confirm whether the incorporation of regulators of complement activity (RCA) into the viral envelope afforded complement resistance, we grew NDV in CHO cells stably transfected with CD46 or HeLa cells, which strongly express CD46 and CD55. NDV grown in RCA-expressing cells was resistant to complement by incorporating CD46 and CD55 on virions. Mammalian CD46 and CD55 molecules on virions exhibited homologous restriction, since chicken sera devoid of neutralizing antibodies to NDV were able to effectively neutralize these virions. The incorporation of chicken RCA into NDV produced in embryonated eggs similarly provided species specificity toward chicken sera.