http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011738
Apobec 3G Efficiently Reduces Infectivity of the Human Exogenous Gammaretrovirus XMRV
Apobec 3G Efficiently Reduces Infectivity of the Human Exogenous Gammaretrovirus XMRV
Kristin Stieler, Nicole Fischer*
Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Eppendorf, Hamburg, Germany
Abstract Top
Background
The 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 Findings
Here 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.
Conclusions
Our 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.
Citation: Stieler K, Fischer N (2010) Apobec 3G Efficiently Reduces Infectivity of the Human Exogenous Gammaretrovirus XMRV. PLoS ONE 5(7): e11738. doi:10.1371/journal.pone.0011738
Editor: Peter Sommer, Institut Pasteur Korea, Republic of Korea
Received: March 8, 2010; Accepted: June 16, 2010; Published: July 23, 2010
Copyright: 2010 Stieler, Fischer. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by the Wilhelm Sander Stiftung, grant 2005/166.1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Eppendorf, Hamburg, Germany
Abstract Top
Background
The 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 Findings
Here 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.
Conclusions
Our 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.
Citation: Stieler K, Fischer N (2010) Apobec 3G Efficiently Reduces Infectivity of the Human Exogenous Gammaretrovirus XMRV. PLoS ONE 5(7): e11738. doi:10.1371/journal.pone.0011738
Editor: Peter Sommer, Institut Pasteur Korea, Republic of Korea
Received: March 8, 2010; Accepted: June 16, 2010; Published: July 23, 2010
Copyright: 2010 Stieler, Fischer. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by the Wilhelm Sander Stiftung, grant 2005/166.1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.