Dispersed and conserved hydrophobic residues of HIV-1 Vif are essential for CBFβ recruitment and A3G suppression

Journal of Virology
Xiaohong ZhouXiao-Fang Yu

Abstract

CBFβ was recently found to be a key regulator of the ability of human immunodeficiency virus type 1 (HIV-1) Vif to overcome host antiviral APOBEC3 proteins. However, the detailed molecular requirements for the Vif-CBFβ interaction are still not clear. Here, we mapped the minimum Vif domain required for CBFβ binding. In terms of CBFβ binding, the Vif N terminus was very sensitive to deletions. We determined that the Vif fragment from residues 5 to 126 was sufficient to form a stable complex with CBFβ in vitro. We also observed that ionic interactions were not the main contributor to the interaction between Vif and CBFβ. Instead, hydrophobic interactions were important for maintaining the Vif-CBFβ complex, since it could be disrupted by nonionic detergent. Site-directed mutagenesis of conserved hydrophobic amino acids revealed novel residues in Vif that were important for CBFβ binding and APOBEC3 inactivation. At least part of the well-characterized HCCH domain (residues 108 to 139) was required to form a stable Vif-CBFβ complex. Thus, the HCCH motif may have a dual role in binding both Cul5 and CBFβ. Considering the importance of Vif in HIV-1 infection, this unique Vif-CBFβ interaction represents an attractive pharmacological in...Continue Reading

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Citations

May 19, 2017·The Journal of General Virology·Youwei AiXiaojun Wang
Sep 14, 2019·Protein Science : a Publication of the Protein Society·Farshad C Azimi, Jeffrey E Lee
May 31, 2020·Viruses·Krista A Delviks-FrankenberryVinay K Pathak
Jan 30, 2021·Frontiers in Microbiology·Daniel J Salamango, Reuben S Harris
May 1, 2021·Viruses·Benjamin StupflerJean-Christophe Paillart

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