Lineage-Specific Viral Hijacking of Non-canonical E3 Ubiquitin Ligase Cofactors in the Evolution of Vif Anti-APOBEC3 Activity
Year: 2015
Type: article
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.
Source: Cell Reports
Authors: 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
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Awards: APOBEC3 Proteins in HIV Restriction, Molecular Biophysics Training Grant, HARC Center: HIV Accessory and Regulatory Complexes, Exploring Design Principles of Cellular Control Circuits, Global innate immune responses to HIV-1 infection, Structure and Function of the Decapping Enzyme Complex, The Impact of Mutation on the Conformations and Recognition of Ubiquitin, APOBEC3 Proteins in HIV Restriction, Critical Interactions of APOBEC3s: Molecular Approaches to Novel HIV Therapies, Integrative Microbiology Program, UCSF-Bay Area Center for AIDS Research
OpenAlex ID: W1762713094