Persistent KSHV Infection Increases EBV-Associated Tumor Formation In Vivo via Enhanced EBV Lytic Gene Expression
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McHugh, Donal, Caduff, Nicole, Barros, Mario Henrique M., Rämer, Patrick C., Raykova, Ana, Murer, Anita, Landtwing, Vanessa, Quast, Isaak, Styles, Christine T., Spohn, Michael , Fowotade, Adeola, Delecluse, Henri-Jacques, Papoudou-Bai, Alexandra, Lee, Yong-Moon, Kim, Jin-Man, Middeldorp, Jaap, Schulz, Thomas F., Cesarman, Ethel, Zbinden, Andrea, Capaul, Riccarda, White, Robert E., Allday, Martin J., Niedobitek, Gerald, Blackbourn, David, Grundhoff, Adam and Münz, Christian (2017) Persistent KSHV Infection Increases EBV-Associated Tumor Formation In Vivo via Enhanced EBV Lytic Gene Expression Cell Host & Microbe, 22 (1). 61-73.e7.
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Persistent KSHV infection.pdf - Accepted version Manuscript Download (32MB) | Preview |
Official URL: https://doi.org/10.1016/j.chom.2017.06.009
Abstract
The human tumor viruses Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) establish persistent infections in B cells. KSHV is linked to primary effusion lymphoma (PEL), and 90% of PELs also contain EBV. Studies on persistent KSHV infection in vivo and the role of EBV co-infection in PEL development have been hampered by the absence of small animal models. We developed mice reconstituted with human immune system components as a model for KSHV infection and find that EBV/KSHV dual infection enhanced KSHV persistence and tumorigenesis. Dual-infected cells displayed a plasma cell-like gene expression pattern similar to PELs. KSHV persisted in EBV-transformed B cells and was associated with lytic EBV gene expression, resulting in increased tumor formation. Evidence of elevated lytic EBV replication was also found in EBV/KSHV dually infected lymphoproliferative disorders in humans. Our data suggest that KSHV augments EBV-associated tumorigenesis via stimulation of lytic EBV replication.
| Item Type: | Article | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Divisions : | Faculty of Health and Medical Sciences > School of Biosciences and Medicine | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Date : | 12 July 2017 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DOI : | 10.1016/j.chom.2017.06.009 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Copyright Disclaimer : | © 2017 Elsevier Inc | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Uncontrolled Keywords : | Epstein-Barr virus; EBV; Kaposi sarcoma-associated herpesvirus; KSHV; Primary effusion lymphoma; Humanized mouse model; B cell lymphoma; Virus-associated lymphoma; Lytic EBV replication | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Depositing User : | Clive Harris | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Date Deposited : | 30 Nov 2017 13:24 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Last Modified : | 13 Jul 2018 02:08 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| URI: | http://epubs.surrey.ac.uk/id/eprint/845075 |
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