Persistent KSHV Infection Increases EBV-Associated Tumor Formation In Vivo via Enhanced EBV Lytic Gene Expression.
Fiche publication
Date publication
juillet 2017
Journal
Cell host & microbe
Auteurs
Membres identifiés du Cancéropôle Est :
Pr DELECLUSE Henri-Jacques
Tous les auteurs :
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
Lien Pubmed
Résumé
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.
Mots clés
B cell lymphoma, EBV, Epstein-Barr virus, KSHV, Kaposi sarcoma-associated herpesvirus, humanized mouse model, lytic EBV replication, primary effusion lymphoma, virus-associated lymphoma
Référence
Cell Host Microbe. 2017 Jul;22(1):61-73.e7