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Bacterial Artificial Chromosomes: A Functional Genomics Tool for the Study of Positive-strand RNA Viruses
Published on: December 29, 2015
A conserved Y-shaped RNA structure in the 3'UTR of chikungunya virus genome as a host-specialized element that
Eugenia Soledad Bardossy1,2, Sebastiano Volpe2, Diego Ezequiel Alvarez1,2
1Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín-CONICET, Buenos Aires, Argentina.
Abstract:
RNA viral genomes compact information into functional RNA structures. Here, using chikungunya virus as a model, we investigated the structural requirements of conserved RNA elements in the 3' untranslated region (3'UTR) for viral replication in mosquito and mammalian cells. Using structural predictions and co-variation analysis, we identified a highly stable and conserved Y-shaped structure (SLY) at the end of the 3'UTR that is duplicated in the Asian lineage. Functional studies with mutant viruses showed that the SLY has host-specific functions during viral replication and evolution. The SLY positively modulates viral replication in mosquito cells but has the opposite effect in mammalian cells. Additional structural/functional analyses showed that maintaining the Y-shaped fold and specific nucleotides in the loop are critical for full SLY functionality and optimal viral replication in mosquito cells. Experimental adaptation of viruses with duplicated SLYs to mammalian cells resulted in the generation of heterogeneous viral populations comprising variants with diverse 3'UTRs, contrasting with the homogeneous populations from viruses without SLY copies. Altogether, our findings constitute the first evidence of an RNA secondary structure in the 3'UTR of chikungunya virus genome that plays host-dependent functions.
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