title: Structure-guided analysis of the human APOBEC3-HIV restrictome.
abstract: Human APOBEC3 (A3) proteins are host-encoded intrinsic restriction factors that inhibit the replication of many retroviral pathogens. Restriction is believed to occur as a result of the DNA cytosine deaminase activity of the A3 proteins; this activity converts cytosines into uracils in single-stranded DNA retroviral replication intermediates. A3 proteins are also equipped with deamination-independent means to restrict retroviruses that work cooperatively with deamination-dependent restriction pathways. A3 proteins substantially bolster the intrinsic immune system by providing a powerful block to the transmission of retroviral pathogens; however, most retroviruses are able to subvert this replicative restriction in their natural host. HIV-1, for instance, evades A3 proteins through the activity of its accessory protein Vif. Here, we summarize data from recent A3 structural and functional studies to provide perspectives into the interactions between cellular A3 proteins and HIV-1 macromolecules throughout the viral replication cycle.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Halil
authors.initials: H
authors.lastname: Aydin
authors.affiliation: Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Taylor
authors.affiliation: Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: jeff.lee@utoronto.ca.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Lee
mesh_terms: D000071478:APOBEC Deaminases; D000595:Amino Acid Sequence; D001665:Binding Sites; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000378:metabolism; D015497:HIV-1 / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019251:Nucleocapsid / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014779:Virus Replication; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D004277:DNA, Single-Stranded; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase