Lineage-Specific Viral Hijacking of Non-canonical E3Ubiquitin 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, Hörour I. Gunnarsson, Adalbjorg Adalbjornsdóttir, James S. Fraser, Reuben S. Harris, Valgerour Andrésdóttir, John D. Gross*, Nevan J. Krogan

*Corresponding author for this work

Research output: Contribution to journalArticle

31 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1236-1250
Number of pages15
JournalCell reports
Volume11
Issue number8
DOIs
StatePublished - May 26 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Kane, J. R., Stanley, D. J., Hultquist, J. F., Johnson, J. R., Mietrach, N., Binning, J. M., Jónsson, S. R., Barelier, S., Newton, B. W., Johnson, T. L., Franks-Skiba, K. E., Li, M., Brown, W. L., Gunnarsson, H. I., Adalbjornsdóttir, A., Fraser, J. S., Harris, R. S., Andrésdóttir, V., Gross, J. D., & Krogan, N. J. (2015). Lineage-Specific Viral Hijacking of Non-canonical E3Ubiquitin Ligase Cofactors in the Evolution of Vif Anti-APOBEC3 Activity. Cell reports, 11(8), 1236-1250. https://doi.org/10.1016/j.celrep.2015.04.038