Ohgimoto Shinji, Ohgimoto Kaori, Niewiesk Stefan, Klagge Ingo M, Pfeuffer Joanna, Johnston Ian C D, Schneider-Schaulies Jürgen, Weidmann Armin, Ter Meulen Volker, Schneider-Schaulies Sibylle
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, D-97078 Würzburg, Germany1.
The Second Department of Internal Medicine, School of Medicine, Mie University, 2-174 Edobashi, Tsu-City, Mie, Japan4.
J Gen Virol. 2001 Aug;82(Pt 8):1835-1844. doi: 10.1099/0022-1317-82-8-1835.
Recombinant measles viruses (MV) in which the authentic glycoprotein genes encoding the fusion and the haemagglutinin (H) proteins of the Edmonston (ED) vaccine strains were swapped singly or doubly for the corresponding genes of a lymphotropic MV wild-type virus (strain WTF) were used previously to investigate MV tropism in cell lines in tissue culture. When these recombinants and their parental strains, the molecular ED-based clone (ED-tag) and WTF, were used to infect cotton rats, only viruses expressing the MV WTF H protein replicated in secondary lymphatic tissues and caused significant immunosuppression. In vitro, viruses containing the ED H protein revealed a tropism for human peripheral blood lymphocytes as documented by enhanced binding and virus production, whereas those containing the WTF H protein replicated well in monocyte-derived dendritic cells (Mo-DC). This did not correlate with more efficient binding of these viruses to DC, but with an enhancement of uptake, virus spread, accumulation of viral antigens and virus production. Thus, replacement of the ED H protein with WTF H protein was sufficient to confer the DC tropism of WTF to ED-tag in vitro. This study suggests that the MV H protein plays an important role in determining cell tropism to immune cells and this may play an important role in the induction of immunosuppression in vivo.
重组麻疹病毒(MV)曾被用于研究组织培养细胞系中的MV嗜性,这些重组病毒是将埃德蒙斯顿(ED)疫苗株编码融合蛋白和血凝素(H)蛋白的原始糖蛋白基因,单个或成对地替换为嗜淋巴细胞MV野生型病毒(WTF株)的相应基因。当用这些重组病毒及其亲本毒株——基于分子ED的克隆(ED-tag)和WTF——感染棉鼠时,只有表达MV WTF H蛋白的病毒能在二级淋巴组织中复制并引起显著的免疫抑制。在体外,含有ED H蛋白的病毒对人外周血淋巴细胞表现出嗜性,增强的结合和病毒产生证明了这一点,而含有WTF H蛋白的病毒在单核细胞衍生的树突状细胞(Mo-DC)中复制良好。这与这些病毒与DC更有效的结合无关,而是与摄取增强、病毒传播、病毒抗原积累和病毒产生有关。因此,用WTF H蛋白替换ED H蛋白足以使ED-tag在体外具有WTF对DC的嗜性。这项研究表明,MV H蛋白在决定对免疫细胞的细胞嗜性中起重要作用,这可能在体内免疫抑制的诱导中起重要作用。