Harris (University of Minnesota, St Paul, MN) and Xiao-Fang Yu (Johns Hopkins University, Baltimore, MD) for kindly providing the BtA3Z2-Z3 and OaA3Z2-Z3 expression constructs and human VHL and eukaryotic expression plasmids. BC box which is critical for its degradation activity. Conclusions A novel zinc binding loop was identified in the BIV Vif protein that is important for the E3 ubiquination activity, suggesting that the degradation of btA3Z2-Z3 by BIV and that of oaA3Z2-Z3 by MVV Vif may need host factors other than CBF-. [1]. The Vif protein counteracts the antiviral activities of the apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3 (APOBEC3 or A3) proteins of the host [2]. These A3 proteins possess broad antiviral activities for many viruses as natural host restriction factors [3-7]. Among the A3 proteins, A3G is the most intensively studied. In the late stage of LY9 viral infection, A3G proteins are packaged into virions and induce dC to dU mutations in newly synthesized minus-strand viral DNA. These mutations cause abnormal expression of viral K-Ras-IN-1 proteins, resulting in disruptions of the viral life cycle [8-10]. The HIV-1 accessory factor Vif plays a critical role in maintaining efficient viral replication in non-permissive cell lines [11]. HIV-1 Vif antagonizes the antiviral activity of the cellular protein A3G by recruiting the transcription cofactor CBF- and ElonginB (EloB)-ElonginC (EloC) to the Cullin5 (Cul5)-Rbx complex to degrade A3G [3,12-18]. The functional domains that Vif uses to form the E3 ligase complex have been reported. The main sites involved in the interaction with A3G and CBF- are in the N-terminal region of Vif [19-23]. The H-x5-C-x17C 18-C-x3 C5-H motif (i.e., HCCH zinc finger) and the PPLPx4L motif (also known as the Cul5 box) in the C-terminal region of HIV-1 Vif mediate selective binding to Cul5 [24-26]. Meanwhile, another C-terminal SLQ(Y/F) LA motif (BC box) downstream of the HCCH domain binds with EloC to assemble the E3 ligase complex [12,27,28]. Mechanisms of the degradation of APOBEC3 proteins induced by SIV Vif and FIV Vif also have been well studied. SIVmac239 Vif recruits the transcription cofactor CBF- and EloB-EloC to the Cul5-Rbx complex, forming the CBF–Cul5-EloB-EloC E3 ubiquitin ligase to degrade the cellular antiviral protein A3G [29,30]. FIV Vif interacts with feline Cul5, EloB and EloC to form an E3 complex K-Ras-IN-1 to induce degradation of fA3s [31]. BIV affects the immune system like many other lentiviruses [32,33], and its name was based on similarities to HIV-1 in genetic, structural, antigenic and biological factors. BIV infects cattle and causes significant but non-persistent infiltrating lymphocytes and follicular hyperplasia in the hemolymph nodes [34]. MVV is also a lentivirus which causes slowly progressive meningoencephalomyelitis and pneumonia in sheep K-Ras-IN-1 [35]. The Vif proteins of BIV and MVV are both indispensable for viral infectivity [36]. The artiodactyl A3 proteins have been reported to have an active N-terminal DNA cytosine deaminase domain, which displays a dinucleotide deamination preference [37]. According to the nonprimate A3 nomenclature, there are four A3 (btA3) proteins: btA3Z1, btA3Z2, btA3Z3, btA3Z2-Z3 and four A3 (oaA3) proteins: oaA3Z1, oaA3Z2, oaA3Z3 and oaA3Z2-Z3. Among the A3 proteins, A3Z2-Z3 is the only double domain protein that displays fully intact levels of lentivirus K-Ras-IN-1 restriction and is neutralized by Vif from several different species [38]. BIV and MVV Vif are known to degrade the host A3 proteins to antagonize their antiviral activity. However, whether the mechanism by which Vif of BIV and MVV neutralize the btA3s and oaA3s, respectively, is similar to that of HIV-1 Vif against human A3G.
Harris (University of Minnesota, St Paul, MN) and Xiao-Fang Yu (Johns Hopkins University, Baltimore, MD) for kindly providing the BtA3Z2-Z3 and OaA3Z2-Z3 expression constructs and human VHL and eukaryotic expression plasmids
