Arenaviridae exoribonuclease presents genomic RNA edition capacity

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

The paradigm of Arenaviridae NP ExoN states that it is involved in innate immunity suppression [37, [60] [61] [62] , through degradation of ds RNAs which would otherwise stimulate the innate immunity response. Several reports have demonstrated that NP is responsible for the degradation of these ds RNAs using the 3'-5' ExoN located at its C-terminus [25, 32, 35, 63] . This ExoN comprises a DEDDh catalytic motif that is completely conserved across the Arenaviridae [35] implying this activity may be a general feature of arenavirus NPs. The ExoN domain is conserved within the family regardless of both the virus pathogenic potential and its ability to suppress efficiently type I IFN, as previously reported for TCRV and MOPV [42, 60, 64] . MOPV is the closest counterpart of 18 386 387 LASV and presents a 73% NP sequence identity with LASV. During LASV infections, the virus targets mainly macrophages (MP) and dendritic (DC) cells [65] , and infections are characterized by high viremia and generalized immune suppression supposedly due to innate immune inhibition by the ExoN domain. Both MOPV and LASV induces strong type I IFN responses in MP and moderately in DC, but contrarily to LASV which abrogates this response, MOPV does not [42, 64] .