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Maedi-visna virus Vif protein uses motifs distinct from HIV-1 Vif to bind zinc and cofactor required for A3 degradation

TitleMaedi-visna virus Vif protein uses motifs distinct from HIV-1 Vif to bind zinc and cofactor required for A3 degradation
Publication TypeJournal Article
Year of Publication2020
AuthorsKnecht, KM, Hu, Y, Rubene, D, Cook, M, Ziegler, SJ, Jónsson, SR, Xiong, Y
JournalJournal of Biological Chemistry
Abstract

The mammalian apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3 or A3) family of cytidine deaminases restrict viral infections by mutating viral DNA and impeding reverse transcription. To overcome this antiviral activity, most lentiviruses express a viral accessory protein called Vif, which recruits A3 proteins to Cullin-RING E3 ubiquitin ligases such as Cul5 for ubiquitylation and subsequent proteasomal degradation. While Vif proteins from primate lentiviruses like HIV-1 utilize the transcription factor CBFβ as a non-canonical cofactor to stabilize the complex, maedi-visna virus (MVV) Vif hijacks cyclophilin A (CypA) instead. Since CBFβ and CypA are both highly conserved among mammals, the requirement for two different cellular cofactors suggests that these two A3-targeting Vif proteins have different biochemical and structural properties. To investigate this topic, we used a combination of in vitro biochemical assays and in vivo A3 degradation assays to study motifs required for MVV Vif to bind zinc ion, Cul5, and the cofactor CypA. Our results demonstrate that while some common motifs between HIV-1 Vif and MVV Vif are involved in recruiting Cul5, different determinants in MVV Vif are required for cofactor binding and stabilization of the E3 ligase complex, such as the zinc-binding motif and N- and C-terminal regions of the protein. Results from this study advance our understanding of the mechanism of MVV Vif recruitment of cellular factors and the evolution of lentiviral Vif proteins.

URLhttps://www.jbc.org/content/early/2020/11/09/jbc.RA120.014479.full.pdf
DOI10.1074/jbc.RA120.014479
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