Increased tumorigenicity of cells carrying recombinant human herpesvirus 8

Abstract

Human herpesvirus 8 (HHV-8) infection is associated with the development of Kaposi's sarcoma and primary effusion lymphoma. The cloning of the HHV-8 genome into a bacterial artificial chromosome (BAC) allows researchers to mutate and identify the relative importance of HHV-8 genes essential for growth and replication in tissue culture systems. However, in vivo models to study the impact of such mutations are very limited. Consequently, the objective of this study was to determine whether cells carrying the HHV-8 BAC would form tumors when injected into mice, enabling the use of this model to assess the influence of viral gene mutation on tumorigenesis. To do so, 293T and 293T-E1 cells carrying recombinant HHV-8 were injected into SCID mice and tumor growth was analyzed. Our results clearly show that mice injected with 293T-E1 cells had a significantly higher tumor incidence level as well as increased tumor volumes and weights compared to mice injected with 293T control cells. Cells carrying the HHV-8 genome grew faster and more aggressively in SCID mice than control 293T cells, highlighting the oncogenic properties of HHV-8. The model presented could therefore be used for the identification of HHV-8 genes contributing to tumorigenesis in the context of the entire viral genome.