Molecular analysis of the virulence attenuation process in Junín virus vaccine genealogy.
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.
Goñi
Sandra Elizabeth
SE
Departamento de Ciencia y Tecnología, LIGBCM, Universidad Nacional de Quilmes, Argentina, Roque Sáenz Peña 352, CP 1876BXD Bernal, Buenos Aires, Argentina.
Iserte
Javier Alonso
JA
Stephan
Betina Inés
BI
Borio
Cristina Silvia
CS
Ghiringhelli
Pablo Daniel
PD
Lozano
Mario Enrique
ME
D001117:Arenaviridae Infections / Q000517:prevention & control; D001483:Base Sequence; D016000:Cluster Analysis; D006801:Humans; D018051:Junin virus / Q000235:genetics* / Q000472:pathogenicity*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010802:Phylogeny; D017354:Point Mutation; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014613:Vaccines, Attenuated; D014765:Viral Vaccines
D012367:RNA, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines