6pcu | pdb_00006pcu
VP8* of a G2P[4] human rotavirus in complex with scFv antibody 9
Structural highlights
Function[Q2VE61_9REOV] Outer capsid protein VP5*: Forms the spike "foot" and "body" and acts as a membrane permeabilization protein that mediates release of viral particles from endosomal compartments into the cytoplasm. During entry, the part of VP5* that protrudes from the virus folds back on itself and reorganizes from a local dimer to a trimer. This reorganization may be linked to membrane penetration by exposing VP5* hydrophobic region. In integrin-dependent strains, VP5* targets the integrin heterodimer ITGA2/ITGB1 for cell attachment.[SAAS:SAAS01043052] Publication Abstract from PubMedWe previously generated 32 rotavirus-specific (RV-specific) recombinant monoclonal antibodies (mAbs) derived from B cells isolated from human intestinal resections. Twenty-four of these mAbs were specific for the VP8* fragment of RV VP4, and most (20 of 24) were non-neutralizing when tested in the conventional MA104 cell-based assay. We reexamined the ability of these mAbs to neutralize RVs in human intestinal epithelial cells including ileal enteroids and HT-29 cells. Most (18 of 20) of the "non-neutralizing" VP8* mAbs efficiently neutralized human RV in HT-29 cells or enteroids. Serum RV neutralization titers in adults and infants were significantly higher in HT-29 than MA104 cells and adsorption of these sera with recombinant VP8* lowered the neutralization titers in HT-29 but not MA104 cells. VP8* mAbs also protected suckling mice from diarrhea in an in vivo challenge model. X-ray crystallographic analysis of one VP8* mAb (mAb9) in complex with human RV VP8* revealed that the mAb interaction site was distinct from the human histo-blood group antigen binding site. Since MA104 cells are the most commonly used cell line to detect anti-RV neutralization activity, these findings suggest that prior vaccine and other studies of human RV neutralization responses may have underestimated the contribution of VP8* antibodies to the overall neutralization titer. Human VP8* mAbs neutralize rotavirus selectively in human intestinal epithelial cells.,Feng N, Hu L, Ding S, Sanyal M, Zhao B, Sankaran B, Ramani S, McNeal M, Yasukawa LL, Song Y, Prasad BVV, Greenberg HB J Clin Invest. 2019 Aug 12;130:3839-3851. doi: 10.1172/JCI128382. eCollection, 2019 Aug 12. PMID:31403468[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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