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

Donal McHugh, Nicole Caduff, Mario Henrique M Barros, Patrick C Rämer, Ana Raykova, Anita Murer, Vanessa Landtwing, Isaak Quast, Christine T Styles, Michael Spohn, Adeola Fowotade, Henri-Jacques Delecluse, Alexandra Papoudou-Bai, Yong-Moon Lee, Jin-Man Kim, Jaap Middeldorp, Thomas F Schulz, Ethel Cesarman, Andrea Zbinden, Riccarda CapaulRobert E White, Martin J Allday, Gerald Niedobitek, David J Blackbourn, Adam Grundhoff, Christian Münz

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)61-73.e7
JournalCell host & microbe
Volume22
Issue number1
DOIs
Publication statusPublished - 12 Jul 2017

Cite this

McHugh, D., Caduff, N., Barros, M. H. M., Rämer, P. C., Raykova, A., Murer, A., ... Münz, C. (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. https://doi.org/10.1016/j.chom.2017.06.009