Cargando…
Differential viral RNA methylation contributes to pathogen blocking in Wolbachia-colonized arthropods
Arthropod endosymbiont Wolbachia pipientis is part of a global biocontrol strategy to reduce the replication of mosquito-borne RNA viruses such as alphaviruses. We previously demonstrated the importance of a host cytosine methyltransferase, DNMT2, in Drosophila and viral RNA as a cellular target dur...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8959158/ https://www.ncbi.nlm.nih.gov/pubmed/35294495 http://dx.doi.org/10.1371/journal.ppat.1010393 |
_version_ | 1784677087500566528 |
---|---|
author | Bhattacharya, Tamanash Yan, Liewei Crawford, John M. Zaher, Hani Newton, Irene L. G. Hardy, Richard W. |
author_facet | Bhattacharya, Tamanash Yan, Liewei Crawford, John M. Zaher, Hani Newton, Irene L. G. Hardy, Richard W. |
author_sort | Bhattacharya, Tamanash |
collection | PubMed |
description | Arthropod endosymbiont Wolbachia pipientis is part of a global biocontrol strategy to reduce the replication of mosquito-borne RNA viruses such as alphaviruses. We previously demonstrated the importance of a host cytosine methyltransferase, DNMT2, in Drosophila and viral RNA as a cellular target during pathogen-blocking. Here we report a role for DNMT2 in Wolbachia-induced alphavirus inhibition in Aedes species. Expression of DNMT2 in mosquito tissues, including the salivary glands, is elevated upon virus infection. Notably, this is suppressed in Wolbachia-colonized animals, coincident with reduced virus replication and decreased infectivity of progeny virus. Ectopic expression of DNMT2 in cultured Aedes cells is proviral, increasing progeny virus infectivity, and this effect of DNMT2 on virus replication and infectivity is dependent on its methyltransferase activity. Finally, examining the effects of Wolbachia on modifications of viral RNA by LC-MS show a decrease in the amount of 5-methylcytosine modification consistent with the down-regulation of DNMT2 in Wolbachia colonized mosquito cells and animals. Collectively, our findings support the conclusion that disruption of 5-methylcytosine modification of viral RNA is a vital mechanism operative in pathogen blocking. These data also emphasize the essential role of epitranscriptomic modifications in regulating fundamental alphavirus replication and transmission processes. |
format | Online Article Text |
id | pubmed-8959158 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-89591582022-03-29 Differential viral RNA methylation contributes to pathogen blocking in Wolbachia-colonized arthropods Bhattacharya, Tamanash Yan, Liewei Crawford, John M. Zaher, Hani Newton, Irene L. G. Hardy, Richard W. PLoS Pathog Research Article Arthropod endosymbiont Wolbachia pipientis is part of a global biocontrol strategy to reduce the replication of mosquito-borne RNA viruses such as alphaviruses. We previously demonstrated the importance of a host cytosine methyltransferase, DNMT2, in Drosophila and viral RNA as a cellular target during pathogen-blocking. Here we report a role for DNMT2 in Wolbachia-induced alphavirus inhibition in Aedes species. Expression of DNMT2 in mosquito tissues, including the salivary glands, is elevated upon virus infection. Notably, this is suppressed in Wolbachia-colonized animals, coincident with reduced virus replication and decreased infectivity of progeny virus. Ectopic expression of DNMT2 in cultured Aedes cells is proviral, increasing progeny virus infectivity, and this effect of DNMT2 on virus replication and infectivity is dependent on its methyltransferase activity. Finally, examining the effects of Wolbachia on modifications of viral RNA by LC-MS show a decrease in the amount of 5-methylcytosine modification consistent with the down-regulation of DNMT2 in Wolbachia colonized mosquito cells and animals. Collectively, our findings support the conclusion that disruption of 5-methylcytosine modification of viral RNA is a vital mechanism operative in pathogen blocking. These data also emphasize the essential role of epitranscriptomic modifications in regulating fundamental alphavirus replication and transmission processes. Public Library of Science 2022-03-16 /pmc/articles/PMC8959158/ /pubmed/35294495 http://dx.doi.org/10.1371/journal.ppat.1010393 Text en © 2022 Bhattacharya et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Bhattacharya, Tamanash Yan, Liewei Crawford, John M. Zaher, Hani Newton, Irene L. G. Hardy, Richard W. Differential viral RNA methylation contributes to pathogen blocking in Wolbachia-colonized arthropods |
title | Differential viral RNA methylation contributes to pathogen blocking in Wolbachia-colonized arthropods |
title_full | Differential viral RNA methylation contributes to pathogen blocking in Wolbachia-colonized arthropods |
title_fullStr | Differential viral RNA methylation contributes to pathogen blocking in Wolbachia-colonized arthropods |
title_full_unstemmed | Differential viral RNA methylation contributes to pathogen blocking in Wolbachia-colonized arthropods |
title_short | Differential viral RNA methylation contributes to pathogen blocking in Wolbachia-colonized arthropods |
title_sort | differential viral rna methylation contributes to pathogen blocking in wolbachia-colonized arthropods |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8959158/ https://www.ncbi.nlm.nih.gov/pubmed/35294495 http://dx.doi.org/10.1371/journal.ppat.1010393 |
work_keys_str_mv | AT bhattacharyatamanash differentialviralrnamethylationcontributestopathogenblockinginwolbachiacolonizedarthropods AT yanliewei differentialviralrnamethylationcontributestopathogenblockinginwolbachiacolonizedarthropods AT crawfordjohnm differentialviralrnamethylationcontributestopathogenblockinginwolbachiacolonizedarthropods AT zaherhani differentialviralrnamethylationcontributestopathogenblockinginwolbachiacolonizedarthropods AT newtonirenelg differentialviralrnamethylationcontributestopathogenblockinginwolbachiacolonizedarthropods AT hardyrichardw differentialviralrnamethylationcontributestopathogenblockinginwolbachiacolonizedarthropods |