Maf/ham1-like pyrophosphatases of non-canonical nucleotides are host-specific partners of viral RNA-dependent RNA polymerases.
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 s...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-02-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1010332 |
| _version_ | 1828375413376679936 |
|---|---|
| author | Adrian A Valli Rafael García López María Ribaya Francisco Javier Martínez Diego García Gómez Beatriz García Irene Gonzalo Alfonso Gonzalez de Prádena Fabio Pasin Inmaculada Montanuy Encarnación Rodríguez-Gonzalo Juan Antonio García |
| author_facet | Adrian A Valli Rafael García López María Ribaya Francisco Javier Martínez Diego García Gómez Beatriz García Irene Gonzalo Alfonso Gonzalez de Prádena Fabio Pasin Inmaculada Montanuy Encarnación Rodríguez-Gonzalo Juan Antonio García |
| author_sort | Adrian A Valli |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:46:17Z |
| format | Article |
| id | doaj.art-9a303ebb2c9c4730bc4223f00140afa7 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-04-14T07:46:17Z |
| publishDate | 2022-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-9a303ebb2c9c4730bc4223f00140afa72022-12-22T02:05:19ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742022-02-01182e101033210.1371/journal.ppat.1010332Maf/ham1-like pyrophosphatases of non-canonical nucleotides are host-specific partners of viral RNA-dependent RNA polymerases.Adrian A ValliRafael García LópezMaría RibayaFrancisco Javier MartínezDiego García GómezBeatriz GarcíaIrene GonzaloAlfonso Gonzalez de PrádenaFabio PasinInmaculada MontanuyEncarnación Rodríguez-GonzaloJuan Antonio GarcíaCassava 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.https://doi.org/10.1371/journal.ppat.1010332 |
| spellingShingle | Adrian A Valli Rafael García López María Ribaya Francisco Javier Martínez Diego García Gómez Beatriz García Irene Gonzalo Alfonso Gonzalez de Prádena Fabio Pasin Inmaculada Montanuy Encarnación Rodríguez-Gonzalo Juan Antonio García Maf/ham1-like pyrophosphatases of non-canonical nucleotides are host-specific partners of viral RNA-dependent RNA polymerases. PLoS Pathogens |
| title | Maf/ham1-like pyrophosphatases of non-canonical nucleotides are host-specific partners of viral RNA-dependent RNA polymerases. |
| title_full | Maf/ham1-like pyrophosphatases of non-canonical nucleotides are host-specific partners of viral RNA-dependent RNA polymerases. |
| title_fullStr | Maf/ham1-like pyrophosphatases of non-canonical nucleotides are host-specific partners of viral RNA-dependent RNA polymerases. |
| title_full_unstemmed | Maf/ham1-like pyrophosphatases of non-canonical nucleotides are host-specific partners of viral RNA-dependent RNA polymerases. |
| title_short | Maf/ham1-like pyrophosphatases of non-canonical nucleotides are host-specific partners of viral RNA-dependent RNA polymerases. |
| title_sort | maf ham1 like pyrophosphatases of non canonical nucleotides are host specific partners of viral rna dependent rna polymerases |
| url | https://doi.org/10.1371/journal.ppat.1010332 |
| work_keys_str_mv | AT adrianavalli mafham1likepyrophosphatasesofnoncanonicalnucleotidesarehostspecificpartnersofviralrnadependentrnapolymerases AT rafaelgarcialopez mafham1likepyrophosphatasesofnoncanonicalnucleotidesarehostspecificpartnersofviralrnadependentrnapolymerases AT mariaribaya mafham1likepyrophosphatasesofnoncanonicalnucleotidesarehostspecificpartnersofviralrnadependentrnapolymerases AT franciscojaviermartinez mafham1likepyrophosphatasesofnoncanonicalnucleotidesarehostspecificpartnersofviralrnadependentrnapolymerases AT diegogarciagomez mafham1likepyrophosphatasesofnoncanonicalnucleotidesarehostspecificpartnersofviralrnadependentrnapolymerases AT beatrizgarcia mafham1likepyrophosphatasesofnoncanonicalnucleotidesarehostspecificpartnersofviralrnadependentrnapolymerases AT irenegonzalo mafham1likepyrophosphatasesofnoncanonicalnucleotidesarehostspecificpartnersofviralrnadependentrnapolymerases AT alfonsogonzalezdepradena mafham1likepyrophosphatasesofnoncanonicalnucleotidesarehostspecificpartnersofviralrnadependentrnapolymerases AT fabiopasin mafham1likepyrophosphatasesofnoncanonicalnucleotidesarehostspecificpartnersofviralrnadependentrnapolymerases AT inmaculadamontanuy mafham1likepyrophosphatasesofnoncanonicalnucleotidesarehostspecificpartnersofviralrnadependentrnapolymerases AT encarnacionrodriguezgonzalo mafham1likepyrophosphatasesofnoncanonicalnucleotidesarehostspecificpartnersofviralrnadependentrnapolymerases AT juanantoniogarcia mafham1likepyrophosphatasesofnoncanonicalnucleotidesarehostspecificpartnersofviralrnadependentrnapolymerases |