Abstract
BackgroundThe human exogenous gammaretrovirus XMRV is thought to be implicated in prostate cancer and chronic fatigue syndrome. Besides pressing epidemiologic questions, the elucidation of the tissue and cell tropism of the virus, as well as its sensitivity to retroviral restriction factors is of fundamental importance. The Apobec3 (A3) proteins, a family of cytidine deaminases, are one important group of host proteins that control primary infection and efficient viral spread.Methodology/Principal FindingsHere we demonstrate that XMRV is resistant to human Apobec 3B, 3C and 3F, while being highly susceptible to the human A3G protein, a factor which is known to confer antiviral activity against most retroviruses. We show that XMRV as well as MoMLV virions package Apobec proteins independent of their specific restriction activity. hA3G was found to be a potent inhibitor of XMRV as well as of MoMLV infectivity. In contrast to MoMLV, XMRV infection can also be partially reduced by low concentrations of mA3. Interestingly, established prostate cancer cell lines, which are highly susceptible to XMRV infection, do not or only weakly express hA3G.ConclusionsOur findings confirm and extend recently published data that show restriction of XMRV infection by hA3G. The results will be of value to explore which cells are infected with XMRV and efficiently support viral spread in vivo. Furthermore, the observation that XMRV infection can be reduced by mA3 is of interest with regard to the current natural reservoir of XMRV infection.
Highlights
XMRV is the first gammaretrovirus identified in a bonafide human infection [1]
Our results show that XMRV infection is highly restricted only by hA3G, whereas hA3B and hA3F do not significantly reduce XMRV or murine leukaemia viruses (MLVs) infection, and that XMRV infection is significantly reduced at low mA3 expression levels, whereas MLV infection is not
We show that XMRV infection, but not infection by MLV, is significantly reduced at low mA3 expression levels
Summary
The virus is associated with up to 23% of all prostate cancers [2] and was recently found in 67% of PBMCs isolated from patients with chronic fatigue syndrome (CFS) [3]. We and others have recently shown that viral restriction can not be fully explained by receptor distribution or LTR-activity, the latter is significantly increased in cells of prostate tissue origin [10,11,12]. This observation, suggests that other cellular factors, e.g. host restriction factors, are likely to be implicated in the control of viral infection in vivo. The Apobec (A3) proteins, a family of cytidine deaminases, are one important group of host proteins that control primary infection and efficient viral spread
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