title: Human and murine APOBEC3s restrict replication of koala retrovirus by different mechanisms.
abstract: BACKGROUND
  Koala retrovirus (KoRV) is an endogenous and exogenous retrovirus of koalas that may cause lymphoma. As for many other gammaretroviruses, the KoRV genome can potentially encode an alternate form of Gag protein, glyco-gag.
  
  
  RESULTS
  In this study, a convenient assay for assessing KoRV infectivity in vitro was employed: the use of DERSE cells (initially developed to search for infectious xenotropic murine leukemia-like viruses). Using infection of DERSE and other human cell lines (HEK293T), no evidence for expression of glyco-gag by KoRV was found, either in expression of glyco-gag protein or changes in infectivity when the putative glyco-gag reading frame was mutated. Since glyco-gag mediates resistance of Moloney murine leukemia virus to the restriction factor APOBEC3, the sensitivity of KoRV (wt or putatively mutant for glyco-gag) to restriction by murine (mA3) or human APOBEC3s was investigated. Both mA3 and hA3G potently inhibited KoRV infectivity. Interestingly, hA3G restriction was accompanied by extensive G → A hypermutation during reverse transcription while mA3 restriction was not. Glyco-gag status did not affect the results.
  
  
  CONCLUSIONS
  These results indicate that the mechanisms of APOBEC3 restriction of KoRV by hA3G and mA3 differ (deamination dependent vs. independent) and glyco-gag does not play a role in the restriction.
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, 92697-3905, USA. nittat@savannahstate.edu.|Cancer Research Institute, University of California, Irvine, Irvine, CA, 92697-3905, USA. nittat@savannahstate.edu.|Department of Biology, Savannah State University, 3219 College St, Savannah, GA, 31404-5254, USA. nittat@savannahstate.edu.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nitta
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, 92697-3905, USA. datha@usc.edu.|Cancer Research Institute, University of California, Irvine, Irvine, CA, 92697-3905, USA. datha@usc.edu.
authors.forename: Dat
authors.initials: D
authors.lastname: Ha
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, 92697-3905, USA. fgalvezp6@gmail.com.|Cancer Research Institute, University of California, Irvine, Irvine, CA, 92697-3905, USA. fgalvezp6@gmail.com.
authors.forename: Felipe
authors.initials: F
authors.lastname: Galvez
authors.affiliation: Laboratory of Signal Transduction, Department of Cell Biology, Institute for Virus Research, Kyoto University, 53 Shogoin-Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan. takavet@gmail.com.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Miyazawa
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, 92697-3905, USA. hyfan@uci.edu.|Cancer Research Institute, University of California, Irvine, Irvine, CA, 92697-3905, USA. hyfan@uci.edu.
authors.forename: Hung
authors.initials: H
authors.lastname: Fan
mesh_terms: D000071478:APOBEC Deaminases; D000595:Amino Acid Sequence; D000818:Animals; D003564:Cytidine Deaminase / Q000378:metabolism*; D043525:Cytosine Deaminase / Q000378:metabolism*; D017988:Gammaretrovirus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D015683:Gene Products, gag / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D016366:Open Reading Frames; D048368:Phascolarctidae / Q000821:virology*; D048348:Reverse Transcription; D016415:Sequence Alignment; D014779:Virus Replication
chemical_list: D015683:Gene Products, gag; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; C503504:Apobec3 protein, mouse; D003564:Cytidine Deaminase