Selective in vitro cytotoxic effect of human cancer cells by bluetongue virus-10.
Bluetongue viruses (BTVs) infect primarily domestic cattle and wild ruminants but have never been shown to infect normal human cells. Thus, humans are sero-negative towards BTVs. The selective and differential effects of BTV serotype 10 (BTV-10) infection were investigated with five cell lines including primary human embryo lung fibroblast (HEL) and primary murine embryos fibroblast(MEF), human hepatic carcinoma 3B cell line (Hep-3B), human lung carcinoma cell line (A549) and mouse fibroblast cell line (NIH 3T3). In this study, comparative analyses of differential cytopathic effects (CPEs), survival rates using different Multiplicities of Infection (MOI), ultra-structural changes by transmission electron microscopy, and the preferential cell cycle changes of infected cells by flow cytometry were made among these cells. Detection of the presence of BTV genome and kinetic analysis of virus titers in TCID50 were also made. We provided the first analytical demonstration and evidence that BTV-10 could selectively infect and degrade human cancer cells but not cultured primary normal cells. No CPE or viral mRNAs could be detected within these normal cells, while various degrees of CPE could be found in Hep-3B and A549, as well as in NIH 3T3 under similar conditions. Before death, BTV-infected human cancer cells were directly arrested in the sub-G1 phase and the diversity of BTV infection as shown by the MTT method had significant difference (F = 95.635, p < 0.01). Above results suggested that this viral dose-dependent cytotoxic effect is caused by both effective virion amplification and induced apoptosis. Cellular distinctive transformation status may contribute to the selectivity. Thus, selective degradation of human cancer cells but not normal diploid cells by the newly discovered oncolytic potential of BTV would provide a very attractive approach for cancer therapy in the future.
Hu
Jun
J
Laboratory of Molecular Virology & Cancer, State Key Laboratory of Virology, Wuhan University School of Medicine, Wuhan 430071, China.
Dong
Chang-Yuan
CY
Li
Joseph K K
JK
Chen
Dong-E
DE
Liang
Ke
K
Liu
Jun
J
D000818:Animals; D017209:Apoptosis; D001820:Bluetongue virus; D002277:Carcinoma / Q000821:virology; D006528:Carcinoma, Hepatocellular / Q000821:virology; D002417:Cattle; D002460:Cell Line; D045744:Cell Line, Tumor; D005347:Fibroblasts / Q000821:virology; D005434:Flow Cytometry; D016193:G1 Phase; D006801:Humans; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000821:virology; D008175:Lung Neoplasms / Q000821:virology; D051379:Mice; D046529:Microscopy, Electron, Transmission; D041681:NIH 3T3 Cells; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses