MODELING OF POLIOVIRUS - HIV-1 ANTIGEN CHIMERAS

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 < 0.001) lower in viable (2062.1 Å3 ± 400.2) than in non-viable (3617 Å3 ± 650.7) constructs. Our results suggest that viable virus will only be formed when antigen chimearas 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 β-barrel of VP1. © 1990.