title: Reassessment of murine APOBEC1 as a retrovirus restriction factor in vivo.
abstract: APOBEC1 is a cytidine deaminase involved in cholesterol metabolism that has been linked to retrovirus restriction, analogous to the evolutionarily-related APOBEC3 proteins. In particular, murine APOBEC1 was shown to inhibit Friend retrovirus (FV) in vitro, generating high levels of C-to-T and G-to-A mutations. These observations raised the possibility that FV infection might be altered in APOBEC1-null mice. To examine this question directly, we infected wild-type and APOBEC1-null mice with FV complex and evaluated acute infection levels. Surprisingly, APOBEC1-null mice exhibited similar cellular infection levels and plasma viremia relative to wild-type mice. Moreover, next-generation sequencing analyses revealed that in contrast to APOBEC3, APOBEC1 did not enhance retroviral C-to-T and G-to-A mutational frequencies in genomic DNA. Thus, APOBEC1 neither inhibited nor significantly drove the molecular evolution of FV in vivo. Our findings reinforce that not all retrovirus restriction factors characterized as potent in vitro may be functionally relevant in vivo.
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Barrett
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Kejun
authors.initials: K
authors.lastname: Guo
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA; Department of Immunology and Microbiology, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Harper
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA; Department of Immunology and Microbiology, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Sam X
authors.initials: SX
authors.lastname: Li
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Heilman
authors.affiliation: Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Nicholas O
authors.initials: NO
authors.lastname: Davidson
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA; Department of Immunology and Microbiology, University of Colorado Denver, Aurora, CO 80045, USA. Electronic address: mario.santiago@ucdenver.edu.
authors.forename: Mario L
authors.initials: ML
authors.lastname: Santiago
mesh_terms: D000071479:APOBEC-1 Deaminase; D000818:Animals; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D005622:Friend murine leukemia virus / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D007942:Leukemia, Experimental / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009154:Mutation; D012192:Retroviridae Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D014412:Tumor Virus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D019562:Viral Load; D014766:Viremia; D014779:Virus Replication
chemical_list: D000071479:APOBEC-1 Deaminase; C000605090:Apobec1 protein, mouse; D003564:Cytidine Deaminase
keywords: APOBEC1; APOBEC3; Deaminase; Friend retrovirus; HIV-1; Hypermutation; Innate immunity; Restriction factor