title: Lineage-Specific Viral Hijacking of Non-canonical E3 Ubiquitin Ligase Cofactors in the Evolution of Vif Anti-APOBEC3 Activity.
abstract: HIV-1 encodes the accessory protein Vif, which hijacks a host Cullin-RING ubiquitin ligase (CRL) complex as well as the non-canonical cofactor CBFβ, to antagonize APOBEC3 antiviral proteins. Non-canonical cofactor recruitment to CRL complexes by viral factors, to date, has only been attributed to HIV-1 Vif. To further study this phenomenon, we employed a comparative approach combining proteomic, biochemical, structural, and virological techniques to investigate Vif complexes across the lentivirus genus, including primate (HIV-1 and simian immunodeficiency virus macaque [SIVmac]) and non-primate (FIV, BIV, and MVV) viruses. We find that CBFβ is completely dispensable for the activity of non-primate lentiviral Vif proteins. Furthermore, we find that BIV Vif requires no cofactor and that MVV Vif requires a novel cofactor, cyclophilin A (CYPA), for stable CRL complex formation and anti-APOBEC3 activity. We propose modular conservation of Vif complexes allows for potential exaptation of functions through the acquisition of non-CRL-associated host cofactors while preserving anti-APOBEC3 activity.
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, QB3, University of California, San Francisco, San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Kane
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Stanley
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, QB3, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Biochemistry, Molecular Biology and Biophysics, Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
authors.forename: Judd F
authors.initials: JF
authors.lastname: Hultquist
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, QB3, University of California, San Francisco, San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Johnson
authors.affiliation: Institute for Experimental Pathology, University of Iceland, Keldur, 112 Reykjavík, Iceland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mietrach
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Binning
authors.affiliation: Institute for Experimental Pathology, University of Iceland, Keldur, 112 Reykjavík, Iceland.
authors.forename: Stefán R
authors.initials: SR
authors.lastname: Jónsson
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Barelier
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, QB3, University of California, San Francisco, San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
authors.forename: Billy W
authors.initials: BW
authors.lastname: Newton
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, QB3, University of California, San Francisco, San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
authors.forename: Tasha L
authors.initials: TL
authors.lastname: Johnson
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, QB3, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Franks-Skiba
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: William L
authors.initials: WL
authors.lastname: Brown
authors.affiliation: Institute for Experimental Pathology, University of Iceland, Keldur, 112 Reykjavík, Iceland.
authors.forename: Hörður I
authors.initials: HI
authors.lastname: Gunnarsson
authors.affiliation: Institute for Experimental Pathology, University of Iceland, Keldur, 112 Reykjavík, Iceland.
authors.forename: Adalbjorg
authors.initials: A
authors.lastname: Adalbjornsdóttir
authors.affiliation: California Institute for Quantitative Biosciences, QB3, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: James S
authors.initials: JS
authors.lastname: Fraser
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Reuben S
authors.initials: RS
authors.lastname: Harris
authors.affiliation: Institute for Experimental Pathology, University of Iceland, Keldur, 112 Reykjavík, Iceland.
authors.forename: Valgerður
authors.initials: V
authors.lastname: Andrésdóttir
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: john.gross@ucsf.edu.
authors.forename: John D
authors.initials: JD
authors.lastname: Gross
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, QB3, University of California, San Francisco, San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA. Electronic address: nevan.krogan@ucsf.edu.
authors.forename: Nevan J
authors.initials: NJ
authors.lastname: Krogan
mesh_terms: D000071478:APOBEC Deaminases; D000818:Animals; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000037:antagonists & inhibitors*; D016346:Gene Products, vif / Q000276:immunology*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D012756:Sheep; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D016346:Gene Products, vif; D044767:Ubiquitin-Protein Ligases; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase