New in vivo model for KSHV infection and primary effusion lymphoma pathogenesis

Text Box:  Persistent KSHV infection increases EBV-associated tumor formation in vivo via enhanced EBV lytic gene expression.


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.

McHugh et al., Cell Host & Microbe 2017, 22(1): 61-73 ( microbe/fulltext/S1931-3128(17)30249-4)