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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 : Maedi-visna virus Vif interactions with cellular factors

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


Title: Maedi-visna virus Vif protein uses motifs distinct from HIV-1 Vif to bind zinc and cofactor required for A3 degradation : Maedi-visna virus Vif interactions with cellular factors
Author: Knecht, Kirsten M
Hu, Yingxia
Rubene, Diana
Cook, Matthew
Ziegler, Samantha J
Jónsson, Stefán Ragnar
Jónsson, Stefán Ragnar
Xiong, Yong
Date: 2021
Language: Icelandic
Scope: 9
University/Institute: Tilraunastöð Háskóla Íslands í meinafræði að Keldum
Series: Journal of Biological Chemistry; 296()
ISSN: 0021-9258
Subject: Maedi-visna; Maedi-visna virus (MVV); Vif; HIV
URI: https://hdl.handle.net/20.500.11815/3505

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Citation:

Knecht , K M , Hu , Y , Rubene , D , Cook , M , Ziegler , S J , Jónsson , S R , Jónsson , S R & Xiong , Y 2021 , ' Maedi-visna virus Vif protein uses motifs distinct from HIV-1 Vif to bind zinc and cofactor required for A3 degradation : Maedi-visna virus Vif interactions with cellular factors ' , Journal of Biological Chemistry , bind. 296 , 100045 , bls. 1-9 .

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 proteincalled the virion infectivity factor (Vif), which recruits A3 proteins to cullin–RING E3 ubiquitin ligases such as cullin-5 (Cul5) for ubiquitylation and subsequent proteasomal degradation. Although Vif proteins from primate lentiviruses such as HIV-1 utilize the transcription factor core-binding factor subunit beta as a noncanonical cofactor to stabilize the complex, the maedi–visna virus (MVV) Vif hijacks cyclophilin A (CypA) instead. Because core-binding factor subunit beta 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 the MVV Vif to bind zinc ion, Cul5, and the cofactor CypA. Our results demonstrate that although some common motifs between the HIV-1 Vif and MVV Vif are involved in recruiting Cul5, different determinants in the 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.

Description:

Funding and additional information K. M. K. was supported by the predoctoral program in Biophysics NIH T32 GM008283. This work was supported by the National Institutes of Health grant AI116313 (to Y. X.) and University of Iceland Research Fund (to S. R. J). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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