Increased tumorigenicity of cells carrying recombinant human herpesvirus 8

Abstract

SummaryHuman 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.

An endothelial cell line infected by Kaposi’s sarcoma–associated herpes virus (KSHV) allows the investigation of Kaposi’s sarcoma and the validation of novel viral inhibitors in vitro and in vivo

“…We observed that indeed the virus-purged cell population lost their tumorigenic potential upon transplantation in vivo. While establishment of KS-like lesions has also been demonstrated in nude mice with the help of other cell systems [33][34][35][36], this study confirms that tumorigenicity of the rKSHV-HuARLT cell system is virus-dependent. Thus, viral proteins are essential for inducing the tumorigenic phenotype which is reverted when the cells are depleted from the virus, 3D sprouting was shown to be useful to study ex vivo angiogenesis [22] as well as the evasion [37] and KSHV-induced invasion of lymph endothelial cells [10].…”

Comprehensive toxicity and immunogenicity studies reveal minimal effects in mice following sustained dosing of extracellular vesicles derived from HEK293T cells

“…The HEK293T cell line is an immortalised line derived from human embryonic kidney, although its phenotype and molecular characteristics are not typical of renal cells [ 44 ]. While it is a non-cancer cell line, HEK293 cells have been demonstrated to grow in immune-compromised mice in vivo to form subcutaneous tumours [ 45 ]. Furthermore, Li et al characterised HEK293T-derived EVs by profiling the protein, mRNA, and miRNA components, and they identified some potentially immunogenic molecules at both RNA and protein levels [ 30 ].…”