6PCU

VP8* of a G2P[4] human rotavirus in complex with scFv antibody 9

Summary for 6PCU

• Entry DOI: 10.2210/pdb6pcu/pdb
• Descriptor: Outer capsid protein VP4, Variable domain of antibody scFv9, GLYCEROL, ... (5 entities in total)
• Functional Keywords: rotavirus, viral protein, antibody, scfv, viral protein-immune system complex, viral protein/immune system
• Biological source: Rotavirus A; More
• Total number of polymer chains: 6
• Total formula weight: 134558.83

Authors

Hu, L.,Venkataram Prasad, B.V. (deposition date: 2019-06-18, release date: 2019-09-04, Last modification date: 2024-10-30)

Primary citation

Feng, N.,Hu, L.,Ding, S.,Sanyal, M.,Zhao, B.,Sankaran, B.,Ramani, S.,McNeal, M.,Yasukawa, L.L.,Song, Y.,Prasad, B.V.V.,Greenberg, H.B.
Human VP8* mAbs neutralize rotavirus selectively in human intestinal epithelial cells.
J.Clin.Invest., 130:3839-3851, 2019

PubMed Abstract: We 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.

PubMed: 31403468
DOI: 10.1172/JCI128382

Experimental method

X-RAY DIFFRACTION (2.4 Å)