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Host cell-mediated selection of influenza C variants

宿主细胞介导的丙型流感病毒变异体选择

基本信息

批准号：
02670191
负责人：
SUGAWARA Kanetsu
金额：
$ 1.41万
依托单位：
Yamagata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

项目摘要

1. To study the influence of the host cell type on the selection of antigenie variants of influenza C virus, six strains were isolated and passaged in the amniotic sac of embryonated hen's eggs or in the HMV-II line of human malignant melanoma cells and were tested for the reactivity with a panel of monoclonal antibodies (MAbs) to the hemagglutininesterase (HE) glycoprotein. It was observed with two strains (Yamagata/4/88, Yamagata/7/88) that the HE protein of the virus serially passaged in HMV-II cells was antigenically distinguishable from that of the virus cultivated in eggs. It was also found that all virus clones obtained after repeated passages of these two strains in HMV-II cells possessed a markedly increased ability to replicate in the cell culture compared to the clones derived from egg-grown virus preparations, although no difference was seen in the ability to grow in eggs between HMV-II cell-and egg-grown virus clones. These observations suggest that isolation and passage o … More f influenza C virus in HMV-II cells sometimes result in the selection of antigenie variants which have the growth advantage in this host cell type.2. To obtain informations about the molecular mechanisms for the selection of antigenic variants in HMV-II cells, the HE gene sequences were determined for the C/Yamagata/4/88 and C/ Yamagata/7/88 strains serially passaged in the cell culture and then compared with the sequences of the viruses passaged exclusively in eggs. The results showed that the C/Yamagata/4/88 and C/Yamagata/7/88 viruses adapted to HMV-II cells had amino acid changes at positions 283(Asp -> Asn)and 212(Glu -> Lys), compared with the viruses cultivated in eggs. Recently, we revealed that the MAb-selected antigenic variants which had the same amino acid changes as those found in HMV-II cell-adapted viruses exhibited the increased affinity to chicken erythrocyte receptors. It appears likely, therefore, that the emergence of antigenic variants which occurred during the passages of the C/Yamagata /4/88 and C/Yamagata/7/88 strains in HMV-II cells is the result of the selection of variants having the increased binding capacity to host cell receptors. Less

1.为了研究宿主细胞类型对丙型流感病毒抗原变异体选择的影响，分离了6株丙型流感病毒，并在鸡胚羊膜囊或人恶性黑色素瘤细胞系HMV-Ⅱ中传代，用一组抗血凝素酯酶（HE）糖蛋白的单克隆抗体（MAbs）检测了它们的反应性。用两个株（Yamagata/4/88、Yamagata/7/88）观察到，在HMV-Ⅱ细胞中连续传代的病毒的HE蛋白与在鸡蛋中培养的病毒的HE蛋白在抗原性上是可区分的。还发现，这两种病毒株在HMV-II细胞中反复传代后获得的所有病毒克隆，与来自卵生长病毒制剂的克隆相比，在细胞培养物中复制的能力显著增加，尽管在HMV-II细胞和卵生长病毒克隆之间的卵生长能力没有差异。这些观察结果表明，隔离和通过 ...更多信息在HMV-II细胞中对C型流感病毒的感染有时会导致选择在这种宿主细胞类型中具有生长优势的抗原变体。为了获得有关HMV-Ⅱ细胞中抗原变异体选择的分子机制的信息，测定了在细胞培养物中连续传代的C/Yamagata/4/88和C/ Yamagata/7/88毒株的HE基因序列，然后与仅在鸡蛋中传代的病毒的序列进行比较。结果表明，适应HMV-Ⅱ细胞的C/Yamagata/4/88和C/Yamagata/7/88病毒与在鸡蛋中培养的病毒相比，在第283位（Asp -> Asn）和第212位（Glu -> Lys）氨基酸发生了变化。最近，我们发现，MAb选择的抗原变异体具有相同的氨基酸变化，发现在HMV-Ⅱ细胞适应病毒表现出增加的亲和力，鸡红细胞受体。因此，在C/Yamagata /4/88和C/Yamagata/7/88株在HMV-II细胞中传代期间出现的抗原性变异体的出现似乎是选择与宿主细胞受体结合能力增加的变异体的结果。少