Rescue from Cloned cDNAs and In Vivo Characterization of Recombinant Pathogenic Romero and Live-Attenuated Candid #1 Strains of Junin Virus, the Causative Agent of Argentine Hemorrhagic Fever Disease
- 15 February 2011
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 85 (4), 1473-1483
- https://doi.org/10.1128/jvi.02102-10
Abstract
The New World arenavirus Junin virus (JUNV) is the causative agent of Argentine hemorrhagic fever (AHF), which is associated with high morbidity and significant mortality. Several pathogenic strains of JUNV have been documented, and a highly attenuated vaccine strain (Candid #1) was generated and used to vaccinate the human population at risk. The identification and functional characterization of viral genetic determinants associated with AHF and Candid #1 attenuation would contribute to the elucidation of the mechanisms contributing to AHF and the development of better vaccines and therapeutics. To this end, we used reverse genetics to rescue the pathogenic Romero and the attenuated Candid #1 strains of JUNV from cloned cDNAs. Both recombinant Candid #1 (rCandid #1) and Romero (rRomero) had the same growth properties and phenotypic features in cultured cells and in vivo as their corresponding parental viruses. Infection with rRomero caused 100% lethality in guinea pigs, whereas rCandid #1 infection was asymptomatic and provided protection against a lethal challenge with Romero. Notably, Romero and Candid #1 trans -acting proteins, L and NP, required for virus RNA replication and gene expression were exchangeable in a minigenome rescue assay. These findings support the feasibility of studies aimed at determining the contribution of each viral gene to JUNV pathogenesis and attenuation. In addition, we rescued Candid #1 viruses with three segments that efficiently expressed foreign genes introduced into their genomes. This finding opens the way for the development of a safe multivalent arenavirus vaccine.Keywords
This publication has 28 references indexed in Scilit:
- Reverse Genetics Generation of Chimeric Infectious Junin/Lassa Virus Is Dependent on Interaction of Homologous Glycoprotein Stable Signal Peptide and G2 Cytoplasmic DomainsJournal of Virology, 2011
- Development of Infectious Clones for Virulent and Avirulent Pichinde Viruses: a Model Virus To Study Arenavirus-Induced Hemorrhagic FeversJournal of Virology, 2009
- Efficient Reverse Genetics Generation of Infectious Junin Viruses Differing in Glycoprotein ProcessingJournal of Virology, 2009
- Generation of recombinant lymphocytic choriomeningitis viruses with trisegmented genomes stably expressing two additional genes of interestProceedings of the National Academy of Sciences of the United States of America, 2009
- Genomic and biological characterization of aggressive and docile strains of lymphocytic choriomeningitis virus rescued from a plasmid-based reverse-genetics systemJournal of General Virology, 2008
- Cellular Factors Required for Lassa Virus BuddingJournal of Virology, 2006
- Viral vectors for use in the development of biodefense vaccinesAdvanced Drug Delivery Reviews, 2005
- Lassa Virus Z Protein Is a Matrix Protein Sufficient for the Release of Virus-Like ParticlesJournal of Virology, 2003
- Virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector T cellsNature, 1993
- Candid No. 1 Argentine Hemorrhagic Fever Vaccine Protects against Lethal Junin Virus Challenge in Rhesus MacaquesIntervirology, 1992