Genetic and Phenotypic Characterization of GII-4 Noroviruses That Circulated during 1987 to 2008
Genetic and Phenotypic Characterization of GII-4 Noroviruses That Circulated during 1987 to 2008
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DOI：
10.1128/jvi.02614-09
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发表时间：
2010-09-15
影响因子：
5.4
通讯作者：
Jiang, Xi
中科院分区：
文献类型：
--
作者：
Yang, Yang;Xia, Ming;Jiang, Xi
近年来，GII-4诺如病毒（NV）中新变体的优势和不断出现，引起了关于宿主免疫和组织血型抗原（HBGAs）在NV进化中的作用的问题。为了解决这些问题，我们对过去十年（1998年至2008年）流行的GII-4变体进行了遗传和表型表征。93 GII-4序列进行了分析，其中，代表6个遗传簇的16株菌株进行进一步表征。HBGA结合特性通过唾液和寡糖结合测定使用P颗粒作为NV衣壳的模型来确定。还通过酶免疫测定（EIA），蛋白质印迹分析，受体阻断试验，使用P-颗粒特异性抗体从免疫小鼠和GII-4病毒感染的患者的抗原特性进行了检查。我们的结果显示，16个GII-4病毒中的15个与所有A、B和O分泌型的唾液结合。寡糖结合试验产生了很大程度上一致的结果，虽然结合亲和力的一些寡糖不同的一些菌株。唯一的非结合物在结合位点有突变。虽然在16种菌株中检测到抗原变异，但也注意到对HBGA结合的显著交叉阻断。序列比对显示HBGA结合界面高度保守，相邻区域存在一些变异。综上所述，我们的数据表明，GII-4识别不同分泌型HBGAs的能力在过去十年中持续存在，这可能解释了GII-4相对于其他基因型的优势。我们的数据还表明宿主免疫和HBGAs在NV进化中起作用。虽然宿主免疫力可以继续驱动NV进行抗原性改变，但是HBGA的功能选择倾向于锁定衣壳/HBGA界面的结构，并且仅允许HBGA结合位点之外的有限变化。讨论了NV演化中这两个因素之间的这种反选择的潜在结果。
The predominance and continual emergence of new variants in GII-4 noroviruses (NVs) in recent years have raised questions about the role of host immunity and histo-blood group antigens (HBGAs) in NV evolution. To address these questions, we performed a genetic and phenotypic characterization of GII-4 variants circulating in the past decade (1998 to 2008). Ninety-three GII-4 sequences were analyzed, and of them, 16 strains representing 6 genetic clusters were selected for further characterization. The HBGA binding properties were determined by both saliva-and oligosaccharide-binding assays using P particles as a model of NV capsid. The antigenic properties were also examined by enzyme immunoassay (EIA), Western blot analysis, and receptor blocking assay, using P-particle-specific antibodies from immunized mice and GII-4 virus-infected patients. Our results showed that 15 of the 16 GII-4 viruses bound to saliva of all A, B, and O secretors. Oligosaccharide binding assays yielded largely consistent results, although the binding affinities to some oligosaccharides varied among some strains. The only nonbinder had a mutation in the binding site. While antigenic variations were detected among the 16 strains, significant cross-blocking on the HBGA binding was also noted. Sequence alignment revealed high conservation of HBGA binding interfaces with some variations in adjacent regions. Taken together, our data suggested that the ability of GII-4 to recognize different secretor HBGAs persisted over the past decade, which may explain the predominance of GII-4 over other genotypes. Our data also indicated that both the host immunity and HBGAs play a role in NV evolution. While host immunity may continue driving NV for antigenic change, the functional selection by the HBGAs tends to lock the architecture of the capsid/HBGA interfaces and allows only limited variations outside the HBGA binding sites. A potential outcome of such counterselection between theses two factors in NV evolution is discussed.