New XMRV paper: : NF-{kappa}B Activation Stimulates Transcription and Replication of Retrovirus XMRV in Human B-Lineage and Prostate Carcinoma Cells

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See below for WPI Comment on this paper:

 

 

Title: NF-{kappa}B Activation Stimulates Transcription and Replication of

Retrovirus XMRV in Human B-Lineage and Prostate Carcinoma Cells

Journal: Journal of Virology

Date: April 2011

Abstract:

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, suggesting that inflammation, EBV infection, and other conditions

leading to NF-{kappa}B activation may promote XMRV spread in humans.

WPI comment:

These results demonstrate that TNF- and EBV LMP1 enhance XMRV replication in

prostate carcinoma and B-lineage cells through the B-1 site in the XMRV LTR,

suggesting that inflammation, EBV infection and other conditions leading to NF-B

activation may promote XMRV spread in humans