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

SANDRA ELIZABETH GOÑI; JAVIER ALONSO ISERTE; BETINA INÉS STEPHAN; CRISTINA SILVIA BORIO; PABLO DANIEL GHIRINGHELLI; MARIO ENRIQUE LOZANO

VIRUS GENES

SPRINGER

Lugar: Berlin; Año: 2010 vol. 40 p. 320 - 328

0920-8569

The Junin virus strain Candid#1 was developedas a live attenuated vaccine for Argentine hemorrhagicfever. In this article, we report sequence information of theL and S RNAs of Juný´n virus Candid#1 and XJ#44 strains,and show the comparisons with the XJ13 wild-type strainand with other Juný´n virus strains, like Romero, IV4454and MC2 strains, and other closely and distantly relatedarenaviruses. Comparisons of the nucleotide and aminoacid sequences of all genes of three strains from the samevaccine genealogy, revealed different point mutations thatcould be associated with the attenuated phenotype. A 91%of the mutations found are consistent with a hypothesis ofprogressive attenuation of virulence from XJ13 to XJ#44and to Candid#1; 39% of mutations were observed inXJ#44 and conserved in Candid#1, while another 52% ofthe mutations appeared only in Candid#1 strain. Theremaining 9% corresponded to reverse mutations in the Lgene. In summary, the present work shows a set of mutationsthat could be related to the virulence attenuationphenomenon. This information will serve as a starting pointto study this biological phenomenon, provided that areverse genetics system for Juný´n virus is developed toallow the generation of infectious virions with specificmutations.