MOUSE ADAPTATION DETERMINANTS OF POLIOVIRUS TYPE-1 ENHANCE VIRAL UNCOATING

Most poliovirus (PV) strains, such as PV type 1/Mahoney, cannot infect the mouse central nervous system. We previously identified two determ inants of mouse adaptation of PV type 1/Mahoney at positions 22 and 31 of the viral capsid proteins VP1 and VP2, respectively (T. Couderc, J . Hogle, H. Le Blay, F. Horaud, and B. Blondel, J. Virol. 67:3808-3817 , 1993). These residues are located on the interior surface of the cap sid. In an attempt to understand the molecular mechanisms of adaptatio n of PV to mice, we investigated the effects of these tno determinants on the viral multiplication cycle in a human cell line. Both determin ants enhanced receptor-mediated conformational changes leading to alte red particles of 135S, one of the first steps of uncoating, and viral internalization. Furthermore, the residue at position 22 of VP1 appear s to facilitate RNA release. These results strongly suggest that these determinants could also facilitate conformational changes mediated by the PV murine receptor and internalization in the mouse nerve cell, t hus allowing PV to overcome its host range restriction. Moreover, both mouse adaptation determinants are responsible for defects in the asse mbly of virions in human cells and affect the thermostability of the v iral particles. Thus, these mouse adaptation determinants appear to co ntrol the balance between the viral capsid plasticity needed for the c onformational changes in the early steps of infection and the structur al requirements which are involved in the assembly and the stability o f virions.