Summary auto-generated
This study characterizes the molecular basis of attenuation in Candid g1, a live attenuated vaccine for Argentine hemorrhagic fever caused by Junin virus. Researchers sequenced the S RNA of Candid g1 and its more virulent ancestors (XJg44 and XJ prototype strain), comparing them to the wild-type MC2 strain and other arenaviruses. The analysis focused on the N (nucleocapsid) and GPC (glycoprotein precursor) genes. While the three related Junin strains shared common insertions/deletions in the G1 region, two amino acid changes unique to Candid g1 in the hydrophobic G2 region resulted in loss of predicted secondary structure β-turns, potentially contributing to attenuation. The N protein showed fewer sequence variations, with one change in Candid g1 affecting predicted secondary structure. The conserved intergenic region showed no differences between strains, while the 5' non-coding region exhibited high variability. The authors conclude this is an initial step toward identifying attenuation markers, noting that complete understanding requires analyzing the L RNA segment and potentially multiple simultaneous mutations affecting virulence.
Key findings
- Two amino acid changes in the G2 hydrophobic region of Candid g1 cause loss of four predicted β-turns in secondary structure, potentially serving as attenuation markers
- The attenuated Candid g1 strain and its more virulent ancestors share common insertions/deletions in the G1 region, indicating these changes alone do not determine virulence
- One amino acid substitution in the N protein of Candid g1 results in loss of two predicted β-turns, with altered net charge potentially affecting RNA interaction
- The intergenic region is completely conserved across all Junin strains tested, suggesting it is highly constrained and unlikely involved in attenuation
- Changes in glycosylation patterns and proteolytic cleavage sites of the GPC protein are not observed, ruling these as attenuation mechanisms in Junin virus
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Abstract
CG Albarino, PD Ghiringhelli, DM Posik, ME Lozano, AM Ambrosio, A Sanchez and V Romanowski
Departamento de Ciencias Biologicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Argentina.
The Junin virus strain Candid #1 was developed as a live attenuated vaccine for Argentine haemorrhagic fever. In this paper we report the nucleotide sequences of S RNA of Candid #1 and its more virulent ancestors XJ#44 and XJ (prototype). Their relationship to Junin virus wild-type MC2 strain and other closely and distantly related arenaviruses was also examined. Comparisons of the nucleotide and amino acid sequences of N and GPC genes from Candid #1 and its progenitor strains revealed some changes that are unique to the vaccine strain. These changes could be provisionally associated with the attenuated phenotype.