Hi, all.
Here's an abstract of a new paper that presents in vitro work that suggests that Epstein-Barr viral infection and inflammation in general may promote replication of XMRV. Verrrry interesting!
Best regards,
Rich
Journal of Virology, April 2011, p. 3179-3186, Vol. 85, No. 7
0022-538X/11/$012.00+0 doi:10.1128/JVI.02333-10
American Society for Microbiology. All Rights Reserved.
NF-{kappa}B Activation Stimulates Transcription and Replication of Retrovirus XMRV in Human B-Lineage and Prostate Carcinoma Cells{triangledown}
Shuhei Sakakibara,1* Kaori Sakakibara,2 and Giovanna Tosato1
Laboratory of Cellular Oncology,1 Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 208922
Received 8 November 2010/ Accepted 20 January 2011
Xenotropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus linked to prostate carcinoma and chronic fatigue syndrome. Here we report that NF-{kappa}B activation can markedly increase XMRV production. The inflammatory cytokine tumor necrosis factor alpha (TNF-{alpha}), which activates NF-{kappa}B, significantly augmented viral Gag protein production in XMRV-infected cells. Reporter assays showed that TNF-{alpha} and Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1), an intrinsic NF-{kappa}B activator, increased long terminal repeat (LTR)-dependent XMRV transcription. We identified two NF-{kappa}B binding sites (designated {kappa}B-1 and {kappa}B-2) in the LTR U3 region of XMRV and demonstrated that both sites bind to the NF-{kappa}B component p65/RelA. Mutation of the {kappa}B-1 site, but not the {kappa}B-2 site, impaired responsiveness to TNF-{alpha} and LMP1 in reporter assays. A mutant XMRV with a mutation at the {kappa}B-1 site replicated significantly less efficiently than the wild-type XMRV in the prostate carcinoma LNCaP, DU145, and PC-3 cell lines, HEK293 cells, the EBV-immortalized cell line IB4, and the Burkitt's lymphoma cell line BJAB. These results demonstrate that TNF-{alpha} and EBV LMP1 enhance XMRV replication in prostate carcinoma and B-lineage cells through the {kappa}B-1 site in the XMRV LTR,![Balloons :balloons: :balloons:](data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7)
Here's an abstract of a new paper that presents in vitro work that suggests that Epstein-Barr viral infection and inflammation in general may promote replication of XMRV. Verrrry interesting!
Best regards,
Rich
Journal of Virology, April 2011, p. 3179-3186, Vol. 85, No. 7
0022-538X/11/$012.00+0 doi:10.1128/JVI.02333-10
American Society for Microbiology. All Rights Reserved.
NF-{kappa}B Activation Stimulates Transcription and Replication of Retrovirus XMRV in Human B-Lineage and Prostate Carcinoma Cells{triangledown}
Shuhei Sakakibara,1* Kaori Sakakibara,2 and Giovanna Tosato1
Laboratory of Cellular Oncology,1 Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 208922
Received 8 November 2010/ Accepted 20 January 2011
Xenotropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus linked to prostate carcinoma and chronic fatigue syndrome. Here we report that NF-{kappa}B activation can markedly increase XMRV production. The inflammatory cytokine tumor necrosis factor alpha (TNF-{alpha}), which activates NF-{kappa}B, significantly augmented viral Gag protein production in XMRV-infected cells. Reporter assays showed that TNF-{alpha} and Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1), an intrinsic NF-{kappa}B activator, increased long terminal repeat (LTR)-dependent XMRV transcription. We identified two NF-{kappa}B binding sites (designated {kappa}B-1 and {kappa}B-2) in the LTR U3 region of XMRV and demonstrated that both sites bind to the NF-{kappa}B component p65/RelA. Mutation of the {kappa}B-1 site, but not the {kappa}B-2 site, impaired responsiveness to TNF-{alpha} and LMP1 in reporter assays. A mutant XMRV with a mutation at the {kappa}B-1 site replicated significantly less efficiently than the wild-type XMRV in the prostate carcinoma LNCaP, DU145, and PC-3 cell lines, HEK293 cells, the EBV-immortalized cell line IB4, and the Burkitt's lymphoma cell line BJAB. These results demonstrate that TNF-{alpha} and EBV LMP1 enhance XMRV replication in prostate carcinoma and B-lineage cells through the {kappa}B-1 site in the XMRV LTR,