Cancer research “suggests inflammation, EBV infection and other conditions leading to NF-kB activation may promote XMRV spread in man”

Abstract: “NF-kappa B Activation Stimulates Transcription and Replication of Xenotropic Murine Leukemia Virus-Related Virus in Human B-lineage and Prostate Carcinoma Cells” – Source: Journal of Virology, Jan 26, 2011

Authors: S Sakakibara, et al., National Cancer Institute

Xenotropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus linked to prostate carcinoma and chronic fatigue syndrome.

Here we report that NF-kappaB [NF-kB] activation can markedly increase XMRV production.

The inflammatory cytokine TNFalpha, which activates NF-?B, significantly augmented viral Gag protein production in XMRV-infected cells.

Reporter assays showed that TNFalpha and Epstein-Barr virus LMP1 (latent membrane protein 1), an intrinsic NF-kB activator, increased LTR-dependent XMRV transcription.

We identify two NF-?B binding sites (designated kB-1 and kB-2) in the long terminal repeat (LTR) U3 region of XMRV, and demonstrate that both sites bind to the NF-?B component p65/RelA.

Mutation of the kB-1 site, but not the kB-2 site, impaired responsiveness to TNFalpha and LMP1 in reporter assays.

A mutant XMRV at the kB-1 site replicated significantly less efficiently than the wild-type XMRV in the prostate carcinoma LNCaP, DU145 and PC3 cell lines, HEK293 cells, the EBV-immortalized cell line IB4 and the Burkitt's lymphoma cell line BJAB.

These results:

• Demonstrate that TNFalpha and EBV LMP1 enhance XMRV replication in prostate carcinoma and B-lineage cells through the kB-1 site in the XMRV LTR,

• Suggesting that inflammation, EBV infection and other conditions leading to NF-kB activation may promote XMRV spread in man.

Source: Journal of Virology, Jan 26, 2011. PMID: 21270144, by Sakakibara S, Sakakibara K, Tosato G. Laboratory of Cellular Oncology, and Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. [Email:]

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