Nonsense-mediated decay controls the reactivation of the oncogenic herpesviruses EBV and KSHV.
The oncogenic human herpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are the causative agents of multiple malignancies. A hallmark of herpesviruses is their biphasic life cycle consisting of latent and lytic infection. In this study, we identified that c...
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Public Library of Science (PLoS)
2021-02-01
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| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001097&type=printable |
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| author | Michiel van Gent Adrian Reich Sadanandan E Velu Michaela U Gack |
| author_facet | Michiel van Gent Adrian Reich Sadanandan E Velu Michaela U Gack |
| author_sort | Michiel van Gent |
| collection | DOAJ |
| description | The oncogenic human herpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are the causative agents of multiple malignancies. A hallmark of herpesviruses is their biphasic life cycle consisting of latent and lytic infection. In this study, we identified that cellular nonsense-mediated decay (NMD), an evolutionarily conserved RNA degradation pathway, critically regulates the latent-to-lytic switch of EBV and KSHV infection. The NMD machinery suppresses EBV and KSHV Rta transactivator expression and promotes maintenance of viral latency by targeting the viral polycistronic transactivator transcripts for degradation through the recognition of features in their 3' UTRs. Treatment with a small-molecule NMD inhibitor potently induced reactivation in a variety of EBV- and KSHV-infected cell types. In conclusion, our results identify NMD as an important host process that controls oncogenic herpesvirus reactivation, which may be targeted for the therapeutic induction of lytic reactivation and the eradication of tumor cells. |
| format | Article |
| id | doaj-art-7ea99c7f5cdc4a29ac5dafc4e345acce |
| institution | Kabale University |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2021-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-7ea99c7f5cdc4a29ac5dafc4e345acce2025-08-20T03:51:30ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852021-02-01192e300109710.1371/journal.pbio.3001097Nonsense-mediated decay controls the reactivation of the oncogenic herpesviruses EBV and KSHV.Michiel van GentAdrian ReichSadanandan E VeluMichaela U GackThe oncogenic human herpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are the causative agents of multiple malignancies. A hallmark of herpesviruses is their biphasic life cycle consisting of latent and lytic infection. In this study, we identified that cellular nonsense-mediated decay (NMD), an evolutionarily conserved RNA degradation pathway, critically regulates the latent-to-lytic switch of EBV and KSHV infection. The NMD machinery suppresses EBV and KSHV Rta transactivator expression and promotes maintenance of viral latency by targeting the viral polycistronic transactivator transcripts for degradation through the recognition of features in their 3' UTRs. Treatment with a small-molecule NMD inhibitor potently induced reactivation in a variety of EBV- and KSHV-infected cell types. In conclusion, our results identify NMD as an important host process that controls oncogenic herpesvirus reactivation, which may be targeted for the therapeutic induction of lytic reactivation and the eradication of tumor cells.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001097&type=printable |
| spellingShingle | Michiel van Gent Adrian Reich Sadanandan E Velu Michaela U Gack Nonsense-mediated decay controls the reactivation of the oncogenic herpesviruses EBV and KSHV. PLoS Biology |
| title | Nonsense-mediated decay controls the reactivation of the oncogenic herpesviruses EBV and KSHV. |
| title_full | Nonsense-mediated decay controls the reactivation of the oncogenic herpesviruses EBV and KSHV. |
| title_fullStr | Nonsense-mediated decay controls the reactivation of the oncogenic herpesviruses EBV and KSHV. |
| title_full_unstemmed | Nonsense-mediated decay controls the reactivation of the oncogenic herpesviruses EBV and KSHV. |
| title_short | Nonsense-mediated decay controls the reactivation of the oncogenic herpesviruses EBV and KSHV. |
| title_sort | nonsense mediated decay controls the reactivation of the oncogenic herpesviruses ebv and kshv |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001097&type=printable |
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