1. Characterization of virulence-associated determinants in the envelope glycoprotein of Pichinde virus.
- Author
-
Kumar N, Wang J, Lan S, Danzy S, McLay Schelde L, Seladi-Schulman J, Ly H, and Liang Y
- Subjects
- Amino Acid Substitution, Animals, Arenaviridae Infections pathology, Cell Line, Disease Models, Animal, Guinea Pigs, Humans, Lassa Fever pathology, Lassa Fever virology, Liver pathology, Mutation, Pichinde virus physiology, Protein Isoforms chemistry, Protein Isoforms genetics, Protein Isoforms metabolism, Protein Subunits chemistry, Protein Subunits metabolism, Viral Envelope Proteins chemistry, Viral Envelope Proteins metabolism, Viral Load, Virulence, Virus Internalization, Arenaviridae Infections virology, Liver virology, Pichinde virus pathogenicity, Protein Subunits genetics, Viral Envelope Proteins genetics
- Abstract
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., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF