A cytoplasmic form of EHMT1N methylates viral proteins to enable inclusion body maturation and efficient viral replication.
Protein lysine methyltransferases (PKMTs) methylate histone and non-histone proteins to regulate biological outcomes such as development and disease including viral infection. While PKMTs have been extensively studied for modulating the antiviral responses via host gene regulation, their role in met...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-11-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3002871 |
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| author | Kriti Kestur Biligiri Nishi Raj Sharma Abhishek Mohanty Debi Prasad Sarkar Praveen Kumar Vemula Shravanti Rampalli |
| author_facet | Kriti Kestur Biligiri Nishi Raj Sharma Abhishek Mohanty Debi Prasad Sarkar Praveen Kumar Vemula Shravanti Rampalli |
| author_sort | Kriti Kestur Biligiri |
| collection | DOAJ |
| description | Protein lysine methyltransferases (PKMTs) methylate histone and non-histone proteins to regulate biological outcomes such as development and disease including viral infection. While PKMTs have been extensively studied for modulating the antiviral responses via host gene regulation, their role in methylation of proteins encoded by viruses and its impact on host-pathogen interactions remain poorly understood. In this study, we discovered distinct nucleo-cytoplasmic form of euchromatic histone methyltransferase 1 (EHMT1N/C), a PKMT, that phase separates into viral inclusion bodies (IBs) upon cytoplasmic RNA-virus infection (Sendai Virus). EHMT1N/C interacts with cytoplasmic EHMT2 and methylates SeV-Nucleoprotein upon infection. Elevated nucleoprotein methylation during infection correlated with coalescence of small IBs into large mature platforms for efficient replication. Inhibition of EHMT activity by pharmacological inhibitors or genetic depletion of EHMT1N/C reduced the size of IBs with a concomitant reduction in replication. Additionally, we also found that EHMT1 condensation is not restricted to SeV alone but was also seen upon pathogenic RNA viral infections caused by Chandipura and Dengue virus. Collectively, our work elucidates a new mechanism by which cytoplasmic EHMT1 acts as proviral host factor to regulate host-pathogen interaction. |
| format | Article |
| id | doaj-art-56e79915d26b4f3d9c69e8b3d5721b58 |
| institution | DOAJ |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Biology |
| spelling | doaj-art-56e79915d26b4f3d9c69e8b3d5721b582025-08-20T02:59:46ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852024-11-012211e300287110.1371/journal.pbio.3002871A cytoplasmic form of EHMT1N methylates viral proteins to enable inclusion body maturation and efficient viral replication.Kriti Kestur BiligiriNishi Raj SharmaAbhishek MohantyDebi Prasad SarkarPraveen Kumar VemulaShravanti RampalliProtein lysine methyltransferases (PKMTs) methylate histone and non-histone proteins to regulate biological outcomes such as development and disease including viral infection. While PKMTs have been extensively studied for modulating the antiviral responses via host gene regulation, their role in methylation of proteins encoded by viruses and its impact on host-pathogen interactions remain poorly understood. In this study, we discovered distinct nucleo-cytoplasmic form of euchromatic histone methyltransferase 1 (EHMT1N/C), a PKMT, that phase separates into viral inclusion bodies (IBs) upon cytoplasmic RNA-virus infection (Sendai Virus). EHMT1N/C interacts with cytoplasmic EHMT2 and methylates SeV-Nucleoprotein upon infection. Elevated nucleoprotein methylation during infection correlated with coalescence of small IBs into large mature platforms for efficient replication. Inhibition of EHMT activity by pharmacological inhibitors or genetic depletion of EHMT1N/C reduced the size of IBs with a concomitant reduction in replication. Additionally, we also found that EHMT1 condensation is not restricted to SeV alone but was also seen upon pathogenic RNA viral infections caused by Chandipura and Dengue virus. Collectively, our work elucidates a new mechanism by which cytoplasmic EHMT1 acts as proviral host factor to regulate host-pathogen interaction.https://doi.org/10.1371/journal.pbio.3002871 |
| spellingShingle | Kriti Kestur Biligiri Nishi Raj Sharma Abhishek Mohanty Debi Prasad Sarkar Praveen Kumar Vemula Shravanti Rampalli A cytoplasmic form of EHMT1N methylates viral proteins to enable inclusion body maturation and efficient viral replication. PLoS Biology |
| title | A cytoplasmic form of EHMT1N methylates viral proteins to enable inclusion body maturation and efficient viral replication. |
| title_full | A cytoplasmic form of EHMT1N methylates viral proteins to enable inclusion body maturation and efficient viral replication. |
| title_fullStr | A cytoplasmic form of EHMT1N methylates viral proteins to enable inclusion body maturation and efficient viral replication. |
| title_full_unstemmed | A cytoplasmic form of EHMT1N methylates viral proteins to enable inclusion body maturation and efficient viral replication. |
| title_short | A cytoplasmic form of EHMT1N methylates viral proteins to enable inclusion body maturation and efficient viral replication. |
| title_sort | cytoplasmic form of ehmt1n methylates viral proteins to enable inclusion body maturation and efficient viral replication |
| url | https://doi.org/10.1371/journal.pbio.3002871 |
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