Human APOBEC3 proteins can inhibit xenotropic murine leukemia virus-related virus infectivity.
Xenotropic murine leukemia virus-related virus (XMRV) is a novel retrovirus, related to murine leukemia virus (MLV), that has been implicated in human disease. If XMRV is indeed able to replicate in humans, then one might predict that XMRV would have developed resistance to human innate antiviral resistance factors such as APOBEC3G (hA3G). In fact, we observed that XMRV and MLV are both highly sensitive to inhibition by hA3G and equally resistant to inhibition by murine APOBEC3. While several human prostate cancer cell lines were found to lack hA3G, stable expression of physiological levels of hA3G rendered these cells refractory to XMRV replication. Few human tissues fail to express hA3G, and we therefore hypothesize that XMRV replicates in one or more hA3G-negative reservoir tissues and/or that human XMRV infections are likely to be rare and potentially of zoonotic origin.
Department of Molecular Genetics and Microbiology and Center for Virology, Duke University Medical Center, Durham, NC 27710, USA.
Hal P
HP
Bogerd
Fengwen
F
Zhang
Paul D
PD
Bieniasz
Bryan R
BR
Cullen
D000071478:APOBEC Deaminases; D000818:Animals; D045744:Cell Line, Tumor; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000145:classification / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D009052:Leukemia Virus, Murine / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D009154:Mutation; D058008:Xenotropic murine leukemia virus-related virus / Q000235:genetics / Q000502:physiology*
D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase