Apobec 3G efficiently reduces infectivity of the human exogenous gammaretrovirus XMRV.
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.


RESULTS
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.
Stieler
Kristin
K
Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Eppendorf, Hamburg, Germany.
Fischer
Nicole
N
D000071478:APOBEC Deaminases; D000071480:APOBEC-3G Deaminase; D000818:Animals; D002460:Cell Line; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism*; D017988:Gammaretrovirus / Q000235:genetics / Q000378:metabolism*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D015778:Minor Histocompatibility Antigens; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger; D012190:Retroviridae / Q000235:genetics; D014407:Tumor Cells, Cultured; D014771:Virion / Q000235:genetics
D015778:Minor Histocompatibility Antigens; D012333:RNA, Messenger; C492906:APOBEC3F protein, human; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; D000071480:APOBEC-3G Deaminase; C502889:APOBEC3 proteins, human; C495794:APOBEC3B protein, human; C495795:APOBEC3C protein, human; C464924:APOBEC3G protein, human; C503504:Apobec3 protein, mouse; D003564:Cytidine Deaminase