We use a small animal model, based on guinea pigs infected with a non-pathogenic Pichinde virus (PICV), to understand the virulence mechanisms of arenavirus infections in the hosts. PICV P2 strain causes a mild febrile reaction in guinea pigs, while P18 causes severe disease with clinical and pathological features reminiscent of Lassa hemorrhagic fever in humans. The envelope glycoproteins (GPC) of P2 and P18 viruses differ at positions 119, 140, and 164, all localized to the receptor-binding G1 subunit. We found that lentiviral pseudotyped virions (VLPs) bearing P18 GPC show more efficient cell entry than those with P2 GPC, and that the E140 residue plays a critical role in this process. Infection of guinea pigs with the recombinant viruses containing the E140K change demonstrated that E140 of GPC is a necessary virulence determinant of P18 infections, possibly by enhancing the ability of virus to enter target cells.
Bibliographical noteFunding Information:
We thank Dr. Johnson (National Animal Disease Center, Ames, IA) for consultation on histopathological analyses of the guinea pig liver samples, Dr. Aronson (University of Texas Medical Branch) for providing P2 and P18 viruses, Dr. Hunter (Emory University) for providing anti-HIV-1 p24 antibody, and Dr. Nunberg (University of Montana) for discussion and sage advice. This work was supported by the NIH grant nos. AI083409 to YL, and R56AI091805 and R01AI093580 to HL.
- Pichinde virus