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

Sebastien F. Emonet, Alexey V. Seregin, Nadezhda E. Yun, Allison L. Poussard, Aida G. Walker, Juan C. De La Torre, Slobodan Paessler

Research output: Contribution to journalArticle

52 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1473-1483
Number of pages11
JournalJournal of Virology
Volume85
Issue number4
DOIs
StatePublished - Feb 2011

Fingerprint

Junin virus
Arenavirus
Fever
Complementary DNA
New World Arenaviruses
Vaccines
Viruses
microbial genetics
Reverse Genetics
viruses
Attenuated Vaccines
Asymptomatic Infections
Viral Genes
vaccine development
Feasibility Studies
live vaccines
at-risk population
Virus Replication
virus replication
lethal genes

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

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. / Emonet, Sebastien F.; Seregin, Alexey V.; Yun, Nadezhda E.; Poussard, Allison L.; Walker, Aida G.; De La Torre, Juan C.; Paessler, Slobodan.

In: Journal of Virology, Vol. 85, No. 4, 02.2011, p. 1473-1483.

Research output: Contribution to journalArticle

Emonet, Sebastien F. ; Seregin, Alexey V. ; Yun, Nadezhda E. ; Poussard, Allison L. ; Walker, Aida G. ; De La Torre, Juan C. ; Paessler, Slobodan. / 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. In: Journal of Virology. 2011 ; Vol. 85, No. 4. pp. 1473-1483.
@article{c3e498ad268a40bfa2111fde67d221eb,
title = "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",
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.",
author = "Emonet, {Sebastien F.} and Seregin, {Alexey V.} and Yun, {Nadezhda E.} and Poussard, {Allison L.} and Walker, {Aida G.} and {De La Torre}, {Juan C.} and Slobodan Paessler",
year = "2011",
month = "2",
doi = "10.1128/JVI.02102-10",
language = "English",
volume = "85",
pages = "1473--1483",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "4",

}

TY - JOUR

T1 - 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

AU - Emonet, Sebastien F.

AU - Seregin, Alexey V.

AU - Yun, Nadezhda E.

AU - Poussard, Allison L.

AU - Walker, Aida G.

AU - De La Torre, Juan C.

AU - Paessler, Slobodan

PY - 2011/2

Y1 - 2011/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=78951490910&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78951490910&partnerID=8YFLogxK

U2 - 10.1128/JVI.02102-10

DO - 10.1128/JVI.02102-10

M3 - Article

C2 - 21123388

AN - SCOPUS:78951490910

VL - 85

SP - 1473

EP - 1483

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 4

ER -