Molecular analysis of the virulence attenuation process in Junín virus vaccine genealogy

• Published in: Virus genes Vol. 40; no. 3; pp. 320 - 328
• Main Authors: Goñi, Sandra Elizabeth, Iserte, Javier Alonso, Stephan, Betina Inés, Borio, Cristina Silvia, Ghiringhelli, Pablo Daniel, Lozano, Mario Enrique
• Format: Journal Article
• Language: English
• Published: Boston Boston : Springer US 01.06.2010; Springer US; Springer Nature B.V
• Subjects: amino acid sequences; Arenaviridae Infections - prevention & control; Base Sequence; Biomedical and Life Sciences; Biomedicine; Cluster Analysis; fever; genes; Humans; Junin virus; Junin virus - genetics; Junin virus - pathogenicity; Medical Microbiology; Models, Molecular; Molecular Sequence Data; Nucleic Acid Conformation; phenotype; Phylogeny; Plant Sciences; Point Mutation; RNA, Viral - genetics; Sequence Analysis, DNA; Sequence Homology; Vaccines, Attenuated; Viral Vaccines; virion; Virology; virulence; viruses; AHF vaccine; Virulence attenuation; Junin virus; Genetic analysis; Arenavirus
• ISSN: 0920-8569; 1572-994X
• DOI: 10.1007/s11262-010-0450-2

The Junín virus strain Candid#1 was developed as a live attenuated vaccine for Argentine hemorrhagic fever. In this article, we report sequence information of the L and S RNAs of Junín virus Candid#1 and XJ#44 strains, and show the comparisons with the XJ13 wild-type strain and with other Junín virus strains, like Romero, IV4454 and MC2 strains, and other closely and distantly related arenaviruses. Comparisons of the nucleotide and amino acid sequences of all genes of three strains from the same vaccine genealogy, revealed different point mutations that could be associated with the attenuated phenotype. A 91% of the mutations found are consistent with a hypothesis of progressive attenuation of virulence from XJ13 to XJ#44 and to Candid#1; 39% of mutations were observed in XJ#44 and conserved in Candid#1, while another 52% of the mutations appeared only in Candid#1 strain. The remaining 9% corresponded to reverse mutations in the L gene. In summary, the present work shows a set of mutations that could be related to the virulence attenuation phenomenon. This information will serve as a starting point to study this biological phenomenon, provided that a reverse genetics system for Junín virus is developed to allow the generation of infectious virions with specific mutations.