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

Persistent KSHV Infection Increases EBV-Associated Tumor Formation In Vivo via Enhanced EBV Lytic Gene Expression.
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McHugh D, Caduff N, Barros MHM, Rämer PC, Raykova A, Murer A, Landtwing V, Quast I, Styles CT, Spohn M, Fowotade A, Delecluse HJ, Papoudou-Bai A, Lee YM, Kim JM, Middeldorp J, Schulz TF, Cesarman E, Zbinden A, Capaul R, White RE, Allday MJ, Niedobitek G, Blackbourn DJ, Grundhoff A, Münz C,


McHugh D, Caduff N, Barros MHM, Rämer PC, Raykova A, Murer A, Landtwing V, Quast I, Styles CT, Spohn M, Fowotade A, Delecluse HJ, Papoudou-Bai A, Lee YM, Kim JM, Middeldorp J, Schulz TF, Cesarman E, Zbinden A, Capaul R, White RE, Allday MJ, Niedobitek G, Blackbourn DJ, Grundhoff A, Münz C, (click to view)

McHugh D, Caduff N, Barros MHM, Rämer PC, Raykova A, Murer A, Landtwing V, Quast I, Styles CT, Spohn M, Fowotade A, Delecluse HJ, Papoudou-Bai A, Lee YM, Kim JM, Middeldorp J, Schulz TF, Cesarman E, Zbinden A, Capaul R, White RE, Allday MJ, Niedobitek G, Blackbourn DJ, Grundhoff A, Münz C,

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Cell host & microbe 22(1) 61-73.e7 pii 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.

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