Downregulation of APOBEC3G by Xenotropic Murine Leukemia-Virus Related
Virus (XMRV) in Prostate Cancer Cell
Author: Abhinav Dey, Chinmay K Mantri, Jui Pandhare-Dash, Bindong Liu,
Siddharth Pratap, Chandravanu Dash
Xenotropic murine leukemia virus (MLV)-related virus (XMRV) is a
gammaretrovirus that was discovered in prostate cancer tissues.
Recently, it has been proposed that XMRV is a laboratory contaminant
and may have originated via a rare recombination event.
Host restriction factor APOBEC3G (A3G) has been reported to severely
restrict XMRV replication in human peripheral blood mononuclear cells.
Interestingly, XMRV infects and replicates efficiently in prostate
cancer cells of epithelial origin.
It has been proposed that due to lack off or very low levels of A3G
protein in these cells XMRV is able to productively replicate in these
cells.FindingsThis report builds on and challenges the published data
on the absence of A3G protein in prostate epithelial cells lines. We
demonstrate presence of A3G in prostate epithelial cell lines (LNCaP
and DU145) by western blot and mass spectrometry.
We believe the discrepancy in A3G detection is due to selection and
sensitivity of A3G antibodies employed in the prior studies. Our
results also indicate that XMRV produced from A3G expressing LNCaP
cells can infect and replicate in target cells.
Most importantly our data reveal downregulation of A3G in XMRV
infected LNCaP and DU145 cells.
Conclusions: We propose that XMRV replicates efficiently in prostate
epithelial cells by downregulating A3G expression. Given that XMRV
lacks accessory proteins such as HIV-1 Vif that are known to
counteract A3G function in human cells, our data suggest a novel
mechanism by which retroviruses can counteract the antiviral effects
of A3G proteins.
Credits/Source: Virology Journal 2011, 8:531
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