TMEM41B is a host factor required for the replication of diverse coronaviruses including SARS-CoV-2.
Antiviral therapeutics are a front-line defense against virally induced diseases. Because viruses frequently mutate to escape direct inhibition of viral proteins, there is interest in targeting the host proteins that the virus must co-opt to complete its replication cycle. However, a detailed unders...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-05-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009599&type=printable |
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| author | Joseph D Trimarco Brook E Heaton Ryan R Chaparian Kaitlyn N Burke Raquel A Binder Gregory C Gray Clare M Smith Vineet D Menachery Nicholas S Heaton |
| author_facet | Joseph D Trimarco Brook E Heaton Ryan R Chaparian Kaitlyn N Burke Raquel A Binder Gregory C Gray Clare M Smith Vineet D Menachery Nicholas S Heaton |
| author_sort | Joseph D Trimarco |
| collection | DOAJ |
| description | Antiviral therapeutics are a front-line defense against virally induced diseases. Because viruses frequently mutate to escape direct inhibition of viral proteins, there is interest in targeting the host proteins that the virus must co-opt to complete its replication cycle. However, a detailed understanding of the interactions between the virus and the host cell is necessary in order to facilitate development of host-directed therapeutics. As a first step, we performed a genome-wide loss of function screen using the alphacoronavirus HCoV-229E to better define the interactions between coronaviruses and host factors. We report the identification and validation of an ER-resident host protein, TMEM41B, as an essential host factor for not only HCoV-229E but also genetically distinct coronaviruses including the pandemic betacoronavirus SARS-CoV-2. We show that the protein is required at an early, but post-receptor engagement, stage of the viral lifecycle. Further, mechanistic studies revealed that although the protein was not enriched at replication complexes, it likely contributes to viral replication complex formation via mobilization of cholesterol and other lipids to facilitate host membrane expansion and curvature. Continued study of TMEM41B and the development of approaches to prevent its function may lead to broad spectrum anti-coronavirus therapeutics. |
| format | Article |
| id | doaj-art-485cd3cfaf524a5b9fa4517614d1a44a |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2021-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-485cd3cfaf524a5b9fa4517614d1a44a2025-08-20T02:54:33ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-05-01175e100959910.1371/journal.ppat.1009599TMEM41B is a host factor required for the replication of diverse coronaviruses including SARS-CoV-2.Joseph D TrimarcoBrook E HeatonRyan R ChaparianKaitlyn N BurkeRaquel A BinderGregory C GrayClare M SmithVineet D MenacheryNicholas S HeatonAntiviral therapeutics are a front-line defense against virally induced diseases. Because viruses frequently mutate to escape direct inhibition of viral proteins, there is interest in targeting the host proteins that the virus must co-opt to complete its replication cycle. However, a detailed understanding of the interactions between the virus and the host cell is necessary in order to facilitate development of host-directed therapeutics. As a first step, we performed a genome-wide loss of function screen using the alphacoronavirus HCoV-229E to better define the interactions between coronaviruses and host factors. We report the identification and validation of an ER-resident host protein, TMEM41B, as an essential host factor for not only HCoV-229E but also genetically distinct coronaviruses including the pandemic betacoronavirus SARS-CoV-2. We show that the protein is required at an early, but post-receptor engagement, stage of the viral lifecycle. Further, mechanistic studies revealed that although the protein was not enriched at replication complexes, it likely contributes to viral replication complex formation via mobilization of cholesterol and other lipids to facilitate host membrane expansion and curvature. Continued study of TMEM41B and the development of approaches to prevent its function may lead to broad spectrum anti-coronavirus therapeutics.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009599&type=printable |
| spellingShingle | Joseph D Trimarco Brook E Heaton Ryan R Chaparian Kaitlyn N Burke Raquel A Binder Gregory C Gray Clare M Smith Vineet D Menachery Nicholas S Heaton TMEM41B is a host factor required for the replication of diverse coronaviruses including SARS-CoV-2. PLoS Pathogens |
| title | TMEM41B is a host factor required for the replication of diverse coronaviruses including SARS-CoV-2. |
| title_full | TMEM41B is a host factor required for the replication of diverse coronaviruses including SARS-CoV-2. |
| title_fullStr | TMEM41B is a host factor required for the replication of diverse coronaviruses including SARS-CoV-2. |
| title_full_unstemmed | TMEM41B is a host factor required for the replication of diverse coronaviruses including SARS-CoV-2. |
| title_short | TMEM41B is a host factor required for the replication of diverse coronaviruses including SARS-CoV-2. |
| title_sort | tmem41b is a host factor required for the replication of diverse coronaviruses including sars cov 2 |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009599&type=printable |
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