Molecular Characterization of Attenuated Junin Virus Variants

Junin virus, one of the few human pathogenic arenaviruses, is the etiologic agent of Argentine hemorrhagic fever AHF. The clinical symptoms of AHF include hematologic, neurologic, cardiovascular, renal and immunologic alterations. The mortality rate may be as high as 30, but early treatment with immune plasma reduces the fatal cases to less than 2. In order to control the endemo-epidemics in the richest farming land in Argentina a collaborative effort conducted by US and Argentine Governments led to the production of a live, attenuated Junin virus vaccine. After rigorous biological testing in rhesus monkeys, the highly attenuated Junin virus variant named Candid 1 was used in human volunteers, followed by an extensive clinical trial in the AHF endemic area. In order to characterize the vaccine strain Candid 1 at the molecular level and initiate studies on the biochemical basis of attenuation of virulence, the glycoprotein precursor GPC gene of this attenuated virus was cloned and sequenced. The flanking 5 and 3 untranslated regions of the GPC gene do not differ significantly from the homologous regions in the S RNA of the wild type MC2 strain. However, major changes in the amino acid sequence occur in the amino terminal region of GPC as a result of several insertions and deletions in the nucleotide sequence.