Department of Molecular Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
Viruses. 2019 Jul 27;11(8):688. doi: 10.3390/v11080688.
Measles virus (MeV) is monotypic. Live virus challenge provokes a broadly protective humoral immune response that neutralizes all known measles genotypes. The two surface glycoproteins, H and F, mediate virus attachment and entry, respectively, and neutralizing antibodies to H are considered the main correlate of protection. Herein, we made improvements to the MeV reverse genetics system and generated a panel of recombinant MeVs in which the globular head domain or stalk region of the H glycoprotein or the entire F protein, or both, were substituted with the corresponding protein domains from canine distemper virus (CDV), a closely related morbillivirus that resists neutralization by measles-immune sera. The viruses were tested for sensitivity to human or guinea pig neutralizing anti-MeV antisera and to ferret anti-CDV antisera. Virus neutralization was mediated by antibodies to both H and F proteins, with H being immunodominant in the case of MeV and F being so in the case of CDV. Additionally, the globular head domains of both MeV and CDV H proteins were immunodominant over their stalk regions. These data shed further light on the factors constraining the evolution of new morbillivirus serotypes.
麻疹病毒(MeV)是单型的。活病毒挑战会引发广泛的保护性体液免疫反应,中和所有已知的麻疹基因型。两种表面糖蛋白,H 和 F,分别介导病毒附着和进入,针对 H 的中和抗体被认为是主要的保护相关因素。在此,我们改进了 MeV 反向遗传学系统,并生成了一组重组 MeVs,其中 H 糖蛋白的球形头部结构域或茎区或整个 F 蛋白,或两者都被来自犬瘟热病毒(CDV)的相应蛋白结构域取代,CDV 是一种密切相关的副粘病毒,能抵抗麻疹免疫血清的中和。这些病毒被测试对人或豚鼠中和抗-MeV 抗血清以及雪貂抗-CD 抗血清的敏感性。病毒中和是由针对 H 和 F 蛋白的抗体介导的,在 MeV 的情况下 H 是免疫显性的,在 CDV 的情况下 F 是免疫显性的。此外,MeV 和 CDV H 蛋白的球形头部结构域都比其茎区更具有免疫显性。这些数据进一步阐明了限制新副粘病毒血清型进化的因素。