Open AccessMaf/ham1-like pyrophosphatases of non-canonical nucleotides are host-specific partners of viral RNA-dependent RNA polymerases
Author(s) -
Adrián Vallí,
Rafael García López,
Maria Victoria C Ribaya,
Francisco Javier Martínez,
Diego García Gómez,
Beatriz García,
Irene Serrano Gonzalo,
Alfonso González de Prádena,
Fabio Pasin,
Inmaculada Montanuy,
Encarnación RodríguezGonzalo,
Juan Antonio Garcı́a
Publication year - 2022
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1010332
Subject(s) - biology , rna , rna dependent rna polymerase , genetics , nucleotide , plant virus , pyrophosphatase , virology , rna polymerase , biochemistry , virus , gene , enzyme
Cassava brown streak disease (CBSD), dubbed the “Ebola of plants”, is a serious threat to food security in Africa caused by two viruses of the family Potyviridae : cassava brown streak virus (CBSV) and Ugandan (U)CBSV. Intriguingly, U/CBSV, along with another member of this family and one secoviridae, are the only known RNA viruses encoding a protein of the Maf/ham1-like family, a group of widespread pyrophosphatase of non-canonical nucleotides (ITPase) expressed by all living organisms. Despite the socio-economic impact of CDSD, the relevance and role of this atypical viral factor has not been yet established. Here, using an infectious cDNA clone and reverse genetics, we demonstrate that UCBSV requires the ITPase activity for infectivity in cassava, but not in the model plant Nicotiana benthamiana . HPLC-MS/MS experiments showed that, quite likely, this host-specific constraint is due to an unexpected high concentration of non-canonical nucleotides in cassava. Finally, protein analyses and experimental evolution of mutant viruses indicated that keeping a fraction of the yielded UCBSV ITPase covalently bound to the viral RNA-dependent RNA polymerase (RdRP) optimizes viral fitness, and this seems to be a feature shared by the other members of the Potyviridae family expressing Maf/ham1-like proteins. All in all, our work (i) reveals that the over-accumulation of non-canonical nucleotides in the host might have a key role in antiviral defense, and (ii) provides the first example of an RdRP-ITPase partnership, reinforcing the idea that RNA viruses are incredibly versatile at adaptation to different host setups.