Functional and Structural Characterization of P[19] Rotavirus VP8* Interaction with Histo-blood Group Antigens

Sun, Xiaoman; Li, Dandi; Peng, Ruchao; Guo, Nan; Jin, Miao; Zhou, Yongkang; Xie, Gary; Pang, Lili; Zhang, Qing; Qi, Jianxun; Duan, Zhaojun

doi:10.1128/jvi.01566-16

Cited by 19 publications

(20 citation statements)

References 43 publications

(170 reference statements)

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“…Trypsin cleavage of the RVs VP4 generates two fragments (VP8* and VP5*); VP8* binds sialic acid (SA), whereas VP5* contains an integrin‐binding motif and a hydrophobic region that facilitate cell membrane penetration and integrin‐binding (Dowling, Denisova, LaMonica, & Mackow, ; Pesavento, Crawford, Estes, & Prasad, ). VP8* of RVs mediates cell attachment by interacting with histo‐blood group antigens (HBGAs) (Hu et al., ; Sun et al., ). The structures of the neutralizing epitopes on the VP5* and VP8* proteins have been identified.…”

Section: Discussionmentioning

confidence: 99%

A G3P[13] porcine group A rotavirus emerging in China is a reassortant and a natural recombinant in the VP4 gene

Jing

Zhang

Shi

et al. 2017

Transbound Emerg Dis

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Group A rotaviruses (RVAs) are a major cause of serious intestinal disease in piglets. In this study, a novel pig strain was identified in a stool sample from China. The strain was designated RVA/Pig/China/LNCY/2016/G3P[13] and had a G3-P[13]-I5-R1-C1-M1-A8-N1-T1-E1-H1 genome. The viral protein 7 (VP7) and non-structural protein 4 (NSP4) genes of RVA/Pig/China/LNCY/2016/G3P[13] were closely related to cogent genes of human RVAs, suggesting that a reassortment between pig and human strains had occurred. Recombination analysis showed that RVA/Pig/China/LNCY/2016/G3P[13] is a natural recombinant strain between the P[23] and P[7] RVA strains, and crossover points for recombination were found at nucleotides (nt) 456 and 804 of the VP4 gene. Elucidating the biological characteristics of porcine rotavirus (PoRV) will be helpful for further analyses of the epidemic characteristics of this virus. The results of this study provide valuable information for RVA recombination and evolution and will facilitate future investigations into the molecular pathogenesis of RVAs.

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Section: Discussionmentioning

confidence: 99%

A G3P[13] porcine group A rotavirus emerging in China is a reassortant and a natural recombinant in the VP4 gene

Jing

Zhang

Shi

et al. 2017

Transbound Emerg Dis

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“…D38054) was cloned into pGEX4T-1 and pET30a vectors with a GST and a His tag, respectively. The recombinant proteins were expressed and purified as described previously (38). The GST fusion and VP8*-His protein were used for functional analysis and crystallization, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…The GST fusion and VP8*-His protein were used for functional analysis and crystallization, respectively. VP8* proteins of porcine P [19] (GenBank accession no.KX455847) (38) and the prevalent human P[6] (5311142) (GenBank accession no. KT162986), human P [4] (11151099) (GenBank accession no.…”

Section: Methodsmentioning

confidence: 99%

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Glycan Binding Specificity and Mechanism of Human and Porcine P[6]/P[19] Rotavirus VP8*s

Sun

et al. 2018

J Virol

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Rotaviruses (RVs), which cause severe gastroenteritis in infants and children, recognize glycan ligands in a genotype-dependent manner via the distal VP8* head of the spike protein VP4. However, the glycan binding mechanisms remain elusive for the P[II] genogroup RVs, including the widely prevalent human RVs (P[8], P[4], and P[6]) and a rare P[19] RV. In this study, we characterized the glycan binding specificities of human and porcine P[6]/P[19] RV VP8*s and found that the P[II] genogroup RV VP8*s could commonly interact with mucin core 2, which may play an important role in RV evolution and cross-species transmission. We determined the first P[6] VP8* structure, as well as the complex structures of human P[19] VP8*, with core 2 and lacto--tetraose (LNT). A glycan binding site was identified in human P[19] VP8*. Structural superimposition and sequence alignment revealed the conservation of the glycan binding site in the P[II] genogroup RV VP8*s. Our data provide significant insight into the glycan binding specificity and glycan binding mechanism of the P[II] genogroup RV VP8*s, which could help in understanding RV evolution, transmission, and epidemiology and in vaccine development. Rotaviruses (RVs), belonging to the family , are double-stranded RNA viruses that cause acute gastroenteritis in children and animals worldwide. Depending on the phylogeny of the VP8* sequences, P[6] and P[19] RVs are grouped into genogroup II, together with P[4] and P[8], which are widely prevalent in humans. In this study, we characterized the glycan binding specificities of human and porcine P[6]/P[19] RV VP8*s, determined the crystal structure of P[6] VP8*, and uncovered the glycan binding pattern in P[19] VP8*, revealing a conserved glycan binding site in the VP8*s of P[II] genogroup RVs by structural superimposition and sequence alignment. Our data suggested that mucin core 2 may play an important role in P[II] RV evolution and cross-species transmission. These data provide insight into the cell attachment, infection, epidemiology, and evolution of P[II] genogroup RVs, which could help in developing control and prevention strategies against RVs.

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“…In addition, the DNA sequence encoding the VP8* core region (residues 64 to 224) of human RVC Bristol was cloned into the pET30a vector (Novagen) with a C-terminal hexahistidine (Hisϫ6) tag. The recombinant proteins were expressed in Escherichia coli strain BL21(DE3) induced with isopropyl-␤-D-thiogalactopyranoside (IPTG) at a final concentration of 0.4 mM at 22°C for 16 h. The GST-and His-tagged proteins were purified as described previously (47). Briefly, the supernatant of bacterial lysates was filtered through a 0.22-mpore-size membrane (Millipore) and then loaded onto a glutathione-Sepharose (GE Healthcare Life Sciences) or HisTrap (GE Healthcare Life Sciences) column.…”

Section: Methodsmentioning

confidence: 99%

Human Group C Rotavirus VP8*s Recognize Type A Histo-Blood Group Antigens as Ligands

Sun

Wang

et al. 2018

J Virol

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Group/species C rotaviruses (RVCs) have been identified as important pathogens of acute gastroenteritis (AGE) in children, family-based outbreaks, as well as animal infections. However, little is known regarding their host-specific interaction, infection, and pathogenesis. In this study, we performed serial studies to characterize the function and structural features of a human G4P[2] RVC VP8* that is responsible for the host receptor interaction. Glycan microarrays demonstrated that the human RVC VP8* recognizes type A histo-blood group antigens (HBGAs), which was confirmed by synthetic glycan-/saliva-based binding assays and hemagglutination of red blood cells, establishing a paradigm of RVC VP8*-glycan interactions. Furthermore, the high-resolution crystal structure of the human RVC VP8* was solved, showing a typical galectin-like structure consisting of two β-sheets but with significant differences from cogent proteins of group A rotaviruses (RVAs). The VP8* in complex with a type A trisaccharide displays a novel ligand binding site that consists of a particular set of amino acid residues of the C-D, G-H, and K-L loops. RVC VP8* interacts with type A HBGAs through a unique mechanism compared with that used by RVAs. Our findings shed light on the host-virus interaction and the coevolution of RVCs and will facilitate the development of specific antivirals and vaccines. Group/species C rotaviruses (RVCs), members of family, infect both humans and animals, but our knowledge about the host factors that control host susceptibility and specificity is rudimentary. In this work, we characterized the glycan binding specificity and structural basis of a human RVC that recognizes type A HBGAs. We found that human RVC VP8*, the rotavirus host ligand binding domain that shares only ∼15% homology with the VP8* domains of RVAs, recognizes type A HBGA at an as-yet-unknown glycan binding site through a mechanism distinct from that used by RVAs. Our new advancements provide insights into RVC-cell attachment, the critical step of virus infection, which will in turn help the development of control and prevention strategies against RVs.

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Functional and Structural Characterization of P[19] Rotavirus VP8* Interaction with Histo-blood Group Antigens

Cited by 19 publications

References 43 publications

A G3P[13] porcine group A rotavirus emerging in China is a reassortant and a natural recombinant in the VP4 gene

A G3P[13] porcine group A rotavirus emerging in China is a reassortant and a natural recombinant in the VP4 gene

Glycan Binding Specificity and Mechanism of Human and Porcine P[6]/P[19] Rotavirus VP8*s

Human Group C Rotavirus VP8*s Recognize Type A Histo-Blood Group Antigens as Ligands

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