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Persistent KSHV Infection Increases EBV-Associated Tumor Formation In Vivo via Enhanced EBV Lytic Gene Expression

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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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
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
McHugh, DonalUNSPECIFIEDUNSPECIFIED
Caduff, NicoleUNSPECIFIEDUNSPECIFIED
Barros, Mario Henrique M.UNSPECIFIEDUNSPECIFIED
Rämer, Patrick C.UNSPECIFIEDUNSPECIFIED
Raykova, AnaUNSPECIFIEDUNSPECIFIED
Murer, AnitaUNSPECIFIEDUNSPECIFIED
Landtwing, VanessaUNSPECIFIEDUNSPECIFIED
Quast, IsaakUNSPECIFIEDUNSPECIFIED
Styles, Christine T.UNSPECIFIEDUNSPECIFIED
Spohn, MichaelUNSPECIFIEDUNSPECIFIED
Fowotade, AdeolaUNSPECIFIEDUNSPECIFIED
Delecluse, Henri-JacquesUNSPECIFIEDUNSPECIFIED
Papoudou-Bai, AlexandraUNSPECIFIEDUNSPECIFIED
Lee, Yong-MoonUNSPECIFIEDUNSPECIFIED
Kim, Jin-ManUNSPECIFIEDUNSPECIFIED
Middeldorp, JaapUNSPECIFIEDUNSPECIFIED
Schulz, Thomas F.UNSPECIFIEDUNSPECIFIED
Cesarman, EthelUNSPECIFIEDUNSPECIFIED
Zbinden, AndreaUNSPECIFIEDUNSPECIFIED
Capaul, RiccardaUNSPECIFIEDUNSPECIFIED
White, Robert E.UNSPECIFIEDUNSPECIFIED
Allday, Martin J.UNSPECIFIEDUNSPECIFIED
Niedobitek, GeraldUNSPECIFIEDUNSPECIFIED
Blackbourn, Davidd.blackbourn@surrey.ac.ukUNSPECIFIED
Grundhoff, AdamUNSPECIFIEDUNSPECIFIED
Münz, ChristianUNSPECIFIEDUNSPECIFIED
Date : 12 July 2017
Identification Number : 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 : 30 Nov 2017 13:24
URI: http://epubs.surrey.ac.uk/id/eprint/845075

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