Cell Reports
(May 2015)
Lineage-Specific Viral Hijacking of Non-canonical E3 Ubiquitin Ligase Cofactors in the Evolution of Vif Anti-APOBEC3 Activity
Joshua R. Kane,
David J. Stanley,
Judd F. Hultquist,
Jeffrey R. Johnson,
Nicole Mietrach,
Jennifer M. Binning,
Stefán R. Jónsson,
Sarah Barelier,
Billy W. Newton,
Tasha L. Johnson,
Kathleen E. Franks-Skiba,
Ming Li,
William L. Brown,
Hörður I. Gunnarsson,
Adalbjorg Adalbjornsdóttir,
James S. Fraser,
Reuben S. Harris,
Valgerður Andrésdóttir,
John D. Gross,
Nevan J. Krogan
Affiliations
Joshua R. Kane
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA
David J. Stanley
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA
Judd F. Hultquist
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA
Jeffrey R. Johnson
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA
Nicole Mietrach
Institute for Experimental Pathology, University of Iceland, Keldur, 112 Reykjavík, Iceland
Jennifer M. Binning
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA
Stefán R. Jónsson
Institute for Experimental Pathology, University of Iceland, Keldur, 112 Reykjavík, Iceland
Sarah Barelier
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA
Billy W. Newton
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA
Tasha L. Johnson
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA
Kathleen E. Franks-Skiba
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA
Ming Li
Department of Biochemistry, Molecular Biology and Biophysics, Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA
William L. Brown
Department of Biochemistry, Molecular Biology and Biophysics, Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA
Hörður I. Gunnarsson
Institute for Experimental Pathology, University of Iceland, Keldur, 112 Reykjavík, Iceland
Adalbjorg Adalbjornsdóttir
Institute for Experimental Pathology, University of Iceland, Keldur, 112 Reykjavík, Iceland
James S. Fraser
California Institute for Quantitative Biosciences, QB3, University of California, San Francisco, San Francisco, CA 94158, USA
Reuben S. Harris
Department of Biochemistry, Molecular Biology and Biophysics, Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA
Valgerður Andrésdóttir
Institute for Experimental Pathology, University of Iceland, Keldur, 112 Reykjavík, Iceland
John D. Gross
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA
Nevan J. Krogan
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA
DOI
https://doi.org/10.1016/j.celrep.2015.04.038
Journal volume & issue
Vol. 11,
no. 8
Abstract
Read online
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.
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