Modelling of poliovirus. HIV-1 antigen chimaeras.
We have used laboratory-based molecular modelling to identify structural features of antigen chimaeras of poliovirus expressing epitopes from human immunodeficiency virus (HIV-1) that may affect virus viability. Chimaeras were constructed by replacement of antigenic site 1 of VP1 by sequences corresponding to epitopes from HIV-1. Loop volume, estimated by approximating the loop to an ellipsoid was significantly (P less than 0.001) lower in viable (2062.1 A3 +/- 400.2) than in non-viable (3617 A3 +/- 650.7) constructs. Our results suggest that viable virus will only be formed when antigen chimeras modified at antigenic site of VP1 have a loop occupying a similar volume in space to that occupied by the antigenic site 1 loop. In addition, the modified loop must fit with the peptide bond angles and distances at the top of the beta-barrel of VP1.
Crabbe
M J
MJ
Department of Microbiology, School of Animal and Microbial Sciences, University of Reading, UK.
Evans
D J
DJ
Almond
J W
JW
D000595:Amino Acid Sequence; D002678:Chimera; D003198:Computer Simulation; D000939:Epitopes / Q000235:genetics; D015488:HIV Antigens / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017955:Poliovirus / Q000235:genetics* / Q000276:immunology; D011487:Protein Conformation; D012995:Solubility
D000939:Epitopes; D015488:HIV Antigens