Maf/ham1-like pyrophosphatases of noncanonical nucleotides are host-specific partners of viral RNA-dependent RNA polymerases
| Autor: | Alfonso Gonzalez, Irene Gonzalo, Inmaculada Montanuy, Adrian Valli, Francisco Javier Martinez, Encarnación Rodríguez-Gonzalo, Beatriz Garcia, Rafael Garcia Lopez, Juan Antonio García, Maria Ribaya, Diego Garcia Gomez, Fabio Pasin |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España), European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Valli, Adrián, Martínez, Francisco Javier, Pasin, Fabio, Rodríguez-Gonzalo, Encarnación, García, Juan Antonio |
| Rok vydání: | 2022 |
| Předmět: |
RNA viruses
Leaves Manihot viruses Immunology Nicotiana benthamiana Microbiology chemistry.chemical_compound ITPase activity Tandem Mass Spectrometry RNA polymerase Virology Secoviridae Genetics Pyrophosphatases Molecular Biology Polymerase Plant Diseases Cassava Reverse transcriptase-polymerase chain reaction biology Microbial mutation Potyviridae Nucleotides RNA food and beverages biology.organism_classification RNA-Dependent RNA Polymerase Reverse genetics Polymerase chain reaction chemistry biology.protein RNA Viral Parasitology Viral genomics |
| Zdroj: | DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria instname |
| Popis: | 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. This work was supported by grants BIO2015-73900-JIN (A.A.V) and BIO2016-80572-R (J.A.G) funded by MCIN/ AEI /10.13039/501100011033/ and by FEDER a way to make Europe; grants PID2019-110979RB-I00 (A.A.V) and PID2019-109380RBI00 (J.A.G) funded by MCIN/ AEI /10.13039/501100011033; and grant RYC2018-025523-I (A.A.V) funded by MCIN/ AEI /10.13039/501100011033 and El FSE invest in your future. |
| Databáze: | OpenAIRE |
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