Arenaviridae exoribonuclease presents genomic RNA edition capacity

Elsie Yekwa; Chutima Aphibanthammakit; Xavier Carnec; Bruno Coutard; Caroline Picard; Bruno Canard; Sylvain Baize; François Ferron

Although the presence of mismatch excision system is logically associated to very large genomes (~30 kb) in Coronaviridae, the presence of such activity, and potentially such RNA repair system, in Arenaviridae of intermediate genome size (~11 kb) remains puzzling. Our results shows a clear diminution of the viral titer for viruses depleted of ExoN activity, but no clear evidence of a drastic increase of mutation in the genome that would lead to catastrophic event. Then what is happening in these mutated viruses? One tentative explanation could be the ExoN is involved in : i) checking and maintaining the sequence integrity of the conserved genomic region at its extremities, and/or ii) the structural integrity of the Intergenic Region (IGR). Indeed, both regions have been previously reported as being critical for viral fitness: i) The conserved region (19 nucleotides) exhibit high degree of sequence conservation at the 3'-termini and is complementary to the 5' end of scenario in which the polymerase is able to incorporate a mismatch but is unable to elongate it, leading to a decrease of suitable genomic material to package, therefore without the ExoN control the number of functional RNP would be reduced and consistent with the loss of viral fitness observed here and else [61, 67] . Therefore we propose that the Arenavirus ExoN is involved in a "limited proof-reading" mechanism driven by structural constraints rather than genomic stability.