Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
J Virol. 2012 Sep;86(18):9899-910. doi: 10.1128/JVI.00979-12. Epub 2012 Jul 3.
The distal portion of rotavirus (RV) VP4 spike protein (VP8*) is implicated in binding to cellular receptors, thereby facilitating viral attachment and entry. While VP8* 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* 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* 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* 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.
轮状病毒（RV）VP4 刺突蛋白（VP8*）的远端部分与细胞受体结合，从而促进病毒附着和进入。虽然一些动物 RV 的 VP8与唾液酸结合，但人类 RV 通常以不依赖唾液酸的方式附着和进入细胞。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，我们对 RV 进行了系统发育分析，并进一步展示了 RV 与 HBGAs 相互作用的变化。根据 VP8序列，RV 分为五个 P 基因组群（P[I]至 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]感染动物和人类。依赖唾液酸的 RV（P[1]、P[2]、P[3]和 P[7]）在 P[I]内形成一个亚群，而三种主要的人类 RV 基因型（P[4]、P[6]和 P[8]）都聚集在 P[II]中。然后，我们对 P[III]中的三种人类 RV（P[9]、P[14]和 P[25]）进行了表征，并观察到与 P[II] RV 不同的新型 A 抗原结合模式。通过使用重组 VP8和天然 RV 进行血凝和唾液结合试验证实了结合。同源建模和突变研究表明，碳水化合物结合界面的位置与依赖唾液酸的 RV 共享，尽管涉及不同的氨基酸。P[III]VP8蛋白还结合猪和牛粘蛋白的 A 抗原，表明 A 抗原可能是 RV 跨种传播的一个因素。我们的研究表明，HBGAs 在 RV 感染和进化中发挥重要作用。
