Abstract
Lentiviruses threaten human and animal health. Virion infectivity factor (Vif) is essential for the infectivity of most lentiviruses, except for the equine infectious anaemia virus (EIAV). Vif promotes viral infectivity by recruiting a Cullin-based E3 ligase to induce the degradation of a class of host restriction factors, named APOBEC3. Core binding factor beta (CBF-β) is necessary for several primate lentiviral Vif functions, including HIV-1 Vif. Although much progress has been made in understanding the contribution of CBF-β to Vif function, the precise mechanism has not yet been fully elucidated. In this study, we found that an interaction with CBF-β altered the oligomerization and subcellular distribution pattern and increased the stability of two primate lentiviral Vifs, HIV-1 Vif and Macaca simian immunodeficiency virus (SIVmac) Vif. Moreover, using a CBF-β loss-of-function mutant, we demonstrated that the interaction between CBF-β and Vif was not sufficient for Vif assistance; a region including F68 in CBF-β was also required for the stability and function of Vif. For the first time, this study separates the binding and regulating processes of CBF-β when it is promoting Vif function, which further extends our understanding of the biochemical regulation of Vif by CBF-β.
Highlights
Common lentiviruses include human immunodeficiency virus (HIV), simian immunodeficiency virus (SIV), feline immunodeficiency virus (FIV), bovine immunodeficiency virus (BIV), caprine arthritis encephalitis virus (CAEV), maedi–visna virus (MVV) and equine infectious anaemia virus (EIAV) [1, 2]
As core binding factor beta (CBF-b) can bind to HIV-1 virion infectivity factor (Vif), regulate the conformation of Vif and inhibit Vif oligomerization, it is possible that CBF-b can affect the formation of HIV-1 Vif puncta
When C terminal double-HA-tagged HIV-1 Vif was overexpressed in HeLa cells, obvious puncta formed in the cytoplasm (Fig. 1a)
Summary
Common lentiviruses include human immunodeficiency virus (HIV), simian immunodeficiency virus (SIV), feline immunodeficiency virus (FIV), bovine immunodeficiency virus (BIV), caprine arthritis encephalitis virus (CAEV), maedi–visna virus (MVV) and equine infectious anaemia virus (EIAV) [1, 2]. Most lentiviruses benefit from Vif protein by recruiting a Cullin–Elongin B/C–Rbxbased E3 ligase to induce cellular restriction factor APOBEC3 family member degradation [5,6,7,8,9,10,11], relieving the lethal G-to-A editing of APOBEC3 to a viral plus genome [6, 12, 13]. CBF-b can interact with HIV-1 Vif protein, increase the biosynthesis and stability of Vif, alter the structural conformation and strengthen the interaction between HIV-1 Vif and Cullin to induce APOBEC3 degradation and increase viral infectivity [14, 20,21,22,23]. Considering the importance of CBF-b to viral fitness, disrupting the interaction between CBF-b and HIV-1 Vif is a target for antiviral therapy
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