Epstein-Barr virus reactivation induces divergent abortive, reprogrammed, and host shutoff states by lytic progression.
Viral infection leads to heterogeneous cellular outcomes ranging from refractory to abortive and fully productive states. Single cell transcriptomics enables a high resolution view of these distinct post-infection states. Here, we have interrogated the host-pathogen dynamics following reactivation o...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-10-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1012341 |
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| author | Elliott D SoRelle Lauren E Haynes Katherine A Willard Beth Chang James Ch'ng Heather Christofk Micah A Luftig |
| author_facet | Elliott D SoRelle Lauren E Haynes Katherine A Willard Beth Chang James Ch'ng Heather Christofk Micah A Luftig |
| author_sort | Elliott D SoRelle |
| collection | DOAJ |
| description | Viral infection leads to heterogeneous cellular outcomes ranging from refractory to abortive and fully productive states. Single cell transcriptomics enables a high resolution view of these distinct post-infection states. Here, we have interrogated the host-pathogen dynamics following reactivation of Epstein-Barr virus (EBV). While benign in most people, EBV is responsible for infectious mononucleosis, up to 2% of human cancers, and is a trigger for the development of multiple sclerosis. Following latency establishment in B cells, EBV reactivates and is shed in saliva to enable infection of new hosts. Beyond its importance for transmission, the lytic cycle is also implicated in EBV-associated oncogenesis. Conversely, induction of lytic reactivation in latent EBV-positive tumors presents a novel therapeutic opportunity. Therefore, defining the dynamics and heterogeneity of EBV lytic reactivation is a high priority to better understand pathogenesis and therapeutic potential. In this study, we applied single-cell techniques to analyze diverse fate trajectories during lytic reactivation in three B cell models. Consistent with prior work, we find that cell cycle and MYC expression correlate with cells refractory to lytic reactivation. We further found that lytic induction yields a continuum from abortive to complete reactivation. Abortive lytic cells upregulate NFκB and IRF3 pathway target genes, while cells that proceed through the full lytic cycle exhibit unexpected expression of genes associated with cellular reprogramming. Distinct subpopulations of lytic cells further displayed variable profiles for transcripts known to escape virus-mediated host shutoff. These data reveal previously unknown and promiscuous outcomes of lytic reactivation with broad implications for viral replication and EBV-associated oncogenesis. |
| format | Article |
| id | doaj-art-beb6fe4dc030459fb40aa1706fd550cb |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-beb6fe4dc030459fb40aa1706fd550cb2025-01-17T05:31:04ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742024-10-012010e101234110.1371/journal.ppat.1012341Epstein-Barr virus reactivation induces divergent abortive, reprogrammed, and host shutoff states by lytic progression.Elliott D SoRelleLauren E HaynesKatherine A WillardBeth ChangJames Ch'ngHeather ChristofkMicah A LuftigViral infection leads to heterogeneous cellular outcomes ranging from refractory to abortive and fully productive states. Single cell transcriptomics enables a high resolution view of these distinct post-infection states. Here, we have interrogated the host-pathogen dynamics following reactivation of Epstein-Barr virus (EBV). While benign in most people, EBV is responsible for infectious mononucleosis, up to 2% of human cancers, and is a trigger for the development of multiple sclerosis. Following latency establishment in B cells, EBV reactivates and is shed in saliva to enable infection of new hosts. Beyond its importance for transmission, the lytic cycle is also implicated in EBV-associated oncogenesis. Conversely, induction of lytic reactivation in latent EBV-positive tumors presents a novel therapeutic opportunity. Therefore, defining the dynamics and heterogeneity of EBV lytic reactivation is a high priority to better understand pathogenesis and therapeutic potential. In this study, we applied single-cell techniques to analyze diverse fate trajectories during lytic reactivation in three B cell models. Consistent with prior work, we find that cell cycle and MYC expression correlate with cells refractory to lytic reactivation. We further found that lytic induction yields a continuum from abortive to complete reactivation. Abortive lytic cells upregulate NFκB and IRF3 pathway target genes, while cells that proceed through the full lytic cycle exhibit unexpected expression of genes associated with cellular reprogramming. Distinct subpopulations of lytic cells further displayed variable profiles for transcripts known to escape virus-mediated host shutoff. These data reveal previously unknown and promiscuous outcomes of lytic reactivation with broad implications for viral replication and EBV-associated oncogenesis.https://doi.org/10.1371/journal.ppat.1012341 |
| spellingShingle | Elliott D SoRelle Lauren E Haynes Katherine A Willard Beth Chang James Ch'ng Heather Christofk Micah A Luftig Epstein-Barr virus reactivation induces divergent abortive, reprogrammed, and host shutoff states by lytic progression. PLoS Pathogens |
| title | Epstein-Barr virus reactivation induces divergent abortive, reprogrammed, and host shutoff states by lytic progression. |
| title_full | Epstein-Barr virus reactivation induces divergent abortive, reprogrammed, and host shutoff states by lytic progression. |
| title_fullStr | Epstein-Barr virus reactivation induces divergent abortive, reprogrammed, and host shutoff states by lytic progression. |
| title_full_unstemmed | Epstein-Barr virus reactivation induces divergent abortive, reprogrammed, and host shutoff states by lytic progression. |
| title_short | Epstein-Barr virus reactivation induces divergent abortive, reprogrammed, and host shutoff states by lytic progression. |
| title_sort | epstein barr virus reactivation induces divergent abortive reprogrammed and host shutoff states by lytic progression |
| url | https://doi.org/10.1371/journal.ppat.1012341 |
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