Rotavirus VP8☆: Phylogeny, Host Range, and Interaction with Histo-Blood Group Antigens
Rotavirus VP8☆: Phylogeny, Host Range, and Interaction with Histo-Blood Group Antigens
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DOI：
10.1128/jvi.00979-12
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发表时间：
2012-09-01
影响因子：
5.4
通讯作者：
Jiang, Xi
中科院分区：
文献类型：
--
作者：
Liu, Yang;Huang, Pengwei;Jiang, Xi
轮状病毒（RV）VP 4刺突蛋白（VP 8（星星））的远端部分涉及与细胞受体的结合，从而促进病毒附着和进入。虽然一些动物RV的VP 8（星星）接合唾液酸，但人RV通常以唾液酸非依赖性方式附着并进入细胞。最近的一项研究表明，主要的人类RV（P[4]，P[6]和P[8]）识别人类组织血型抗原（HBGAs）。在这项研究中，我们进行了RV的系统发育分析，并显示了RV与HBGAs相互作用的进一步变化。根据VP 8（星星）序列，RV分为5个P基因组（P[I]~ P[V]），其中P[I]、P[IV]和P[V]主要感染动物，P[II]感染人类，P[III]既感染动物又感染人类。唾液酸依赖性RV（P[1]、P[2]、P[3]和P[7]）在P [I]内形成亚群，而人RV的所有三种主要P基因型（P[4]、P[6]和P[8]）在P[II]中聚集。然后，我们在P[III]中表征了三种人RV（P[9]、P[14]和P[25]），并观察到与A型抗原结合的新模式，其与P[II] RV的结合模式不同。通过使用重组VP 8（星星）和天然RV的血凝和唾液结合测定来证明结合。同源建模和突变研究表明，糖结合界面的位置与唾液酸依赖性RV共享，尽管涉及不同的氨基酸。P[III] VP 8（星星）蛋白还结合猪和牛粘蛋白的A抗原，表明A抗原可能是RV跨物种传播的因素。我们的研究表明，HBGAs在RV感染和进化中起着重要作用。
The distal portion of rotavirus (RV) VP4 spike protein (VP8(star)) is implicated in binding to cellular receptors, thereby facilitating viral attachment and entry. While VP8(star) of some animal RVs engage sialic acid, human RVs often attach to and enter cells in a sialic acid-independent manner. A recent study demonstrated that the major human RVs (P[4], P[6], and P[8]) recognize human histo-blood group antigens (HBGAs). In this study, we performed a phylogenetic analysis of RVs and showed further variations of RV interaction with HBGAs. On the basis of the VP8(star) sequences, RVs are grouped into five P genogroups (P[I] to P[V]), of which P[I], P[IV], and P[V] mainly infect animals, P[II] infects humans, and P[III] infects both animals and humans. The sialic acid-dependent RVs (P[1], P[2], P[3], and P[7]) form a subcluster within P [I], while all three major P genotypes of human RVs (P[4], P[6], and P[8]) are clustered in P[II]. We then characterized three human RVs (P[9], P[14], and P[25]) in P[III] and observed a new pattern of binding to the type A antigen which is distinct from that of the P[II] RVs. The binding was demonstrated by hemagglutination and saliva binding assay using recombinant VP8(star) and native RVs. Homology modeling and mutagenesis study showed that the locations of the carbohydrate binding interfaces are shared with the sialic acid-dependent RVs, although different amino acids are involved. The P[III] VP8(star) proteins also bind the A antigens of the porcine and bovine mucins, suggesting the A antigen as a possible factor for cross-species transmission of RVs. Our study suggests that HBGAs play an important role in RV infection and evolution.