Epstein-Barr virus reactivation induces divergent abortive, reprogrammed, and host shutoff states by lytic progression.

Autor: SoRelle ED; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, United States of America.; Duke Center for Virology, Durham, North Carolina, United States of America., Haynes LE; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, United States of America.; Duke Center for Virology, Durham, North Carolina, United States of America., Willard KA; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, United States of America.; Duke Center for Virology, Durham, North Carolina, United States of America., Chang B; Department of Integrative Immunobiology, Duke University School of Medicine, Durham, North Carolina, United States of America., Ch'ng J; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, California, United States of America., Christofk H; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, California, United States of America.; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California, United States of America., Luftig MA; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, United States of America.; Duke Center for Virology, Durham, North Carolina, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 Oct 24; Vol. 20 (10), pp. e1012341. Date of Electronic Publication: 2024 Oct 24 (Print Publication: 2024).
DOI: 10.1371/journal.ppat.1012341
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 SoRelle et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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