Watching Every Step of the Way: Junín Virus Attenuation Markers in the Vaccine Lineage
Betina Inés Stephan, Mario Enrique Lozano and Sandra Elizabeth Goñi
Affiliation: Área de Virosis Emergentes y Zoonóticas, Laboratorio de Biología Celular y Molecular, Universidad Nacional de Quilmes, Argentina.
The Arenaviridae family includes several hemorrhagic fever viruses which are important emerging pathogens.
Junín virus, a member of this family, is the etiological agent of Argentine Hemorrhagic Fever (AHF). A collaboration between
the Governments of Argentina and the USA rendered the attenuated Junín virus vaccine strain Candid#1. Arenaviruses
are enveloped viruses with genomes consisting of two single-stranded RNA species (L and S), each carrying two
coding regions separated by a stably structured, non-coding intergenic region. Molecular characterization of the vaccine
strain and of its more virulent ancestors, XJ13 (prototype) and XJ#44, allows a systematic approach for the discovery of
key elements in virulence attenuation. We show comparisons of sequence information for the S RNA of the strains XJ13,
XJ#44 and Candid#1 of Junín virus, along with other strains from the vaccine lineage and a set of Junín virus field strains
collected at the AHF endemic area. Comparisons of nucleotide and amino acid sequences revealed different point mutations
which might be linked to the attenuated phenotype. The majority of changes are consistent with a progressive attenuation
of virulence between XJ13, XJ#44 and Candid#1. We propose that changes found in genomic regions with low
natural variation frequencies are more likely to be associated with the virulence attenuation process. We partially sequenced
field strains to analyze the genomic variability naturally occurring for Junín virus. This information, together
with the sequence analysis of strains with intermediate virulence, will serve as a starting point to study the molecular
bases for viral attenuation.
Keywords: Arenaviridae, Junín virus, Natural variability, Point mutations, Vaccine lineage, Viral attenuation.
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