EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription.
Productive infection by herpesviruses involve the disabling of host-cell intrinsic defenses by viral encoded tegument proteins. Epstein-Barr Virus (EBV) typically establishes a non-productive, latent infection and it remains unclear how it confronts the host-cell intrinsic defenses that restrict vir...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-11-01
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| Series: | PLoS Pathogens |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22102817/pdf/?tool=EBI |
| _version_ | 1818735382725918720 |
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| author | Kevin Tsai Nadezhda Thikmyanova Jason A Wojcechowskyj Henri-Jacques Delecluse Paul M Lieberman |
| author_facet | Kevin Tsai Nadezhda Thikmyanova Jason A Wojcechowskyj Henri-Jacques Delecluse Paul M Lieberman |
| author_sort | Kevin Tsai |
| collection | DOAJ |
| description | Productive infection by herpesviruses involve the disabling of host-cell intrinsic defenses by viral encoded tegument proteins. Epstein-Barr Virus (EBV) typically establishes a non-productive, latent infection and it remains unclear how it confronts the host-cell intrinsic defenses that restrict viral gene expression. Here, we show that the EBV major tegument protein BNRF1 targets host-cell intrinsic defense proteins and promotes viral early gene activation. Specifically, we demonstrate that BNRF1 interacts with the host nuclear protein Daxx at PML nuclear bodies (PML-NBs) and disrupts the formation of the Daxx-ATRX chromatin remodeling complex. We mapped the Daxx interaction domain on BNRF1, and show that this domain is important for supporting EBV primary infection. Through reverse transcription PCR and infection assays, we show that BNRF1 supports viral gene expression upon early infection, and that this function is dependent on the Daxx-interaction domain. Lastly, we show that knockdown of Daxx and ATRX induces reactivation of EBV from latently infected lymphoblastoid cell lines (LCLs), suggesting that Daxx and ATRX play a role in the regulation of viral chromatin. Taken together, our data demonstrate an important role of BNRF1 in supporting EBV early infection by interacting with Daxx and ATRX; and suggest that tegument disruption of PML-NB-associated antiviral resistances is a universal requirement for herpesvirus infection in the nucleus. |
| first_indexed | 2024-12-18T00:20:22Z |
| format | Article |
| id | doaj.art-3621579e6a134f919202e24efd4386eb |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-18T00:20:22Z |
| publishDate | 2011-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-3621579e6a134f919202e24efd4386eb2022-12-21T21:27:21ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742011-11-01711e100237610.1371/journal.ppat.1002376EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription.Kevin TsaiNadezhda ThikmyanovaJason A WojcechowskyjHenri-Jacques DeleclusePaul M LiebermanProductive infection by herpesviruses involve the disabling of host-cell intrinsic defenses by viral encoded tegument proteins. Epstein-Barr Virus (EBV) typically establishes a non-productive, latent infection and it remains unclear how it confronts the host-cell intrinsic defenses that restrict viral gene expression. Here, we show that the EBV major tegument protein BNRF1 targets host-cell intrinsic defense proteins and promotes viral early gene activation. Specifically, we demonstrate that BNRF1 interacts with the host nuclear protein Daxx at PML nuclear bodies (PML-NBs) and disrupts the formation of the Daxx-ATRX chromatin remodeling complex. We mapped the Daxx interaction domain on BNRF1, and show that this domain is important for supporting EBV primary infection. Through reverse transcription PCR and infection assays, we show that BNRF1 supports viral gene expression upon early infection, and that this function is dependent on the Daxx-interaction domain. Lastly, we show that knockdown of Daxx and ATRX induces reactivation of EBV from latently infected lymphoblastoid cell lines (LCLs), suggesting that Daxx and ATRX play a role in the regulation of viral chromatin. Taken together, our data demonstrate an important role of BNRF1 in supporting EBV early infection by interacting with Daxx and ATRX; and suggest that tegument disruption of PML-NB-associated antiviral resistances is a universal requirement for herpesvirus infection in the nucleus.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22102817/pdf/?tool=EBI |
| spellingShingle | Kevin Tsai Nadezhda Thikmyanova Jason A Wojcechowskyj Henri-Jacques Delecluse Paul M Lieberman EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription. PLoS Pathogens |
| title | EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription. |
| title_full | EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription. |
| title_fullStr | EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription. |
| title_full_unstemmed | EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription. |
| title_short | EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription. |
| title_sort | ebv tegument protein bnrf1 disrupts daxx atrx to activate viral early gene transcription |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22102817/pdf/?tool=EBI |
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