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Updated: Jun 10, 2026
Transduction of Human Cells with Polymer-complexed Ecotropic Lentivirus for Enhanced Biosafety
Published on: July 24, 2011
Apobec 3G efficiently reduces infectivity of the human exogenous gammaretrovirus XMRV
Kristin Stieler1, Nicole Fischer
1Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Eppendorf, Hamburg, Germany.
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.
Insights
Human Apobec 3G (hA3G) restricts Xenotropic Murine Leukemia Virus-Related Retrovirus (XMRV) infection, a virus linked to prostate cancer. Prostate cancer cells often lack hA3G, potentially explaining XMRV susceptibility.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Xenotropic Murine Leukemia Virus-Related Retrovirus (XMRV) is a human gammaretrovirus associated with prostate cancer and chronic fatigue syndrome.
- Understanding XMRV's tissue tropism and susceptibility to host restriction factors is crucial.
- Apobec3 (A3) proteins are key host factors that inhibit retroviral infection and spread.
Purpose of the Study:
- To investigate the sensitivity of XMRV to various human Apobec3 (hA3) proteins.
- To determine the role of hA3G in restricting XMRV infection.
- To assess hA3G expression in prostate cancer cell lines.
Main Methods:
- Testing XMRV and Moloney murine leukemia virus (MoMLV) infectivity in the presence of different hA3 proteins.
- Analyzing Apobec protein packaging into virions.
- Quantifying hA3G expression in prostate cancer cell lines.
Main Results:
- XMRV is resistant to hA3B, hA3C, and hA3F, but highly susceptible to hA3G.
- hA3G potently inhibits XMRV and MoMLV infectivity.
- Prostate cancer cell lines susceptible to XMRV show low or no hA3G expression.
- XMRV infection is partially reduced by mouse Apobec 3 (mA3).
Conclusions:
- hA3G is a significant restriction factor for XMRV, confirming and extending previous findings.
- The low expression of hA3G in prostate cancer cells may facilitate XMRV infection and spread.
- The susceptibility of XMRV to mA3 warrants further investigation regarding the natural reservoir of XMRV infection.
