Reassortant analysis of guinea pig virulence of Pichinde virus variants

The new world arenavirus Pichinde (PIC) is the basis of an accepted small a nimal model for human Lassa fever. PIC (Munchique strain) variant P2 is att enuated in guinea pigs, whereas variant P18 is extremely virulent. Previous sequence analysis of the S segments of these two viruses indicated a small number of possible virulence markers in the glycoprotein precursor (GPC) a nd nucleoprotein (NP) genes. In order to determine the role of these S segm ent genes in guinea pig virulence in this system, we have generated reassor tant viruses. When tested in outbred guinea pigs, the reassortant containin g the S segment from the virulent parent P18 (S18L2) caused significantly h igher morbidity than the reciprocal reassortant. This increased morbidity w as associated with higher viral titers in serum and spleen. However, the S1 8L2 reassortant was not as fully virulent in this system as the P18 parent, indicating a role for L segment genes in virulence. (C) 2001 Academic Pres s.