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Publication Abstract from PubMed

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 specificity of human and porcine P[6]/P[19] RV VP8* and found that the P[II] genogroup RV VP8*s could commonly interact with mucin core 2 which may play an important role in the 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-N-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 would help understanding of RV evolution, transmission, epidemiology, and vaccine approach.IMPORTANCERotaviruses (RVs), belonging to the family Reoviridae, are double-stranded RNA viruses causing acute gastroenteritis in children and animals worldwide. Depending on phylogeny of the VP8* sequences, P[6] and P[19] RVs are grouped into the genogroup II together with P[4] and P[8] that are widely prevalent in humans. In this study, we characterized the glycan binding specificity 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 the P[II] RV evolution and cross-species transmission. These data provide insight into cell attachment, infection, epidemiology, and evolution of P[II] genogroup RVs, which would help to develop control and prevention strategies against RVs.

Glycan Binding Specificity and Mechanism of Human and Porcine P[6]/P[19] Rotavirus VP8*s.,Sun X, Li D, Qi J, Chai W, Wang L, Wang L, Peng R, Wang H, Zhang Q, Pang L, Kong X, Wang H, Jin M, Gao GF, Duan Z J Virol. 2018 May 2. pii: JVI.00538-18. doi: 10.1128/JVI.00538-18. PMID:29720519^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.