Identification of a Cullin5-ElonginB-ElonginC E3 Complex in Degradation of Feline Immunodeficiency Virus Vif-Mediated Feline APOBEC3 Proteins

Wang, Jiawen; Zhang, Wenyan; Lv, Mingyu; Zuo, Tao; Kong, Wei; Yu, Xianghui

doi:10.1128/jvi.05218-11

Cited by 30 publications

(63 citation statements)

References 64 publications

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“…FIV Vif interacts with CUL5 and Elongin B/C to form an E3 complex that degrades feline APOBEC3 through a proteasome-dependent pathway (49). This is very similar to the action of HIV-1 and simian immunodeficiency virus (SIV) Vif.…”

mentioning

confidence: 77%

“…In addition, BIV Vif and MVV Vif inefficiently interact with CUL5 (21). Although FIV Vif could coprecipitate with CUL5, the direct interaction between FIV Vif and CUL5 is unclear (49). Thus, it needs to be determined whether FIV Vif can directly recruit CUL5 or whether the interaction is mediated by Elongin B/C.…”

Section: Discussionmentioning

confidence: 99%

“…The CBF-␤ gene sequence was submitted to GenBank under accession number KM250107. (49,52). To test if feline CBF-␤ interacts with FIV Vif, we first cloned the CBF-␤ gene from a Chinese domestic cat.…”

Section: Cbf-␤-kd 293t Cell Generationmentioning

confidence: 99%

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Core-Binding Factor Subunit Beta Is Not Required for Non-Primate Lentiviral Vif-Mediated APOBEC3 Degradation

Zhu

Wang

et al. 2014

J Virol

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Viral infectivity factor (Vif) is required for lentivirus fitness and pathogenicity, except in equine infectious anemia virus (EIAV).Vif enhances viral infectivity by a Cullin5-Elongin B/C E3 complex to inactivate the host restriction factor APOBEC3. Corebinding factor subunit beta (CBF-␤) is a cell factor that was recently shown to be important for the primate lentiviral Vif function. Non-primate lentiviral Vif also degrades APOBEC3 through the proteasome pathway. However, it is unclear whether CBF-␤ is required for the non-primate lentiviral Vif function. In this study, we demonstrated that the Vifs of non-primate lentiviruses, including feline immunodeficiency virus (FIV), bovine immunodeficiency virus (BIV), caprine arthritis encephalitis virus (CAEV), and maedi-visna virus (MVV), do not interact with CBF-␤. In addition, CBF-␤ did not promote the stability of FIV, BIV, CAEV, and MVV Vifs. Furthermore, CBF-␤ silencing or overexpression did not affect non-primate lentiviral Vif-mediated APOBEC3 degradation. Our results suggest that non-primate lentiviral Vif induces APOBEC3 degradation through a different mechanism than primate lentiviral Vif. IMPORTANCEThe APOBEC3 protein family members are host restriction factors that block retrovirus replication. Vif, an accessory protein of lentivirus, degrades APOBEC3 to rescue viral infectivity by forming Cullin5-Elongin B/C-based E3 complex. CBF-␤ was proved to be a novel regulator of primate lentiviral Vif function. In this study, we found that CBF-␤ knockdown or overexpression did not affect FIV Vif's function, which induced polyubiquitination and degradation of APOBEC3 by recruiting the E3 complex in a manner similar to that of HIV-1 Vif. We also showed that other non-primate lentiviral Vifs did not require CBF-␤ to degrade APOBEC3. CBF-␤ did not interact with non-primate lentiviral Vifs or promote their stability. These results suggest that a different mechanism exists for the Vif-APOBEC interaction and that non-primates are not suitable animal models for exploring pharmacological interventions that disrupt Vif-CBF-␤ interaction.

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confidence: 77%

Section: Discussionmentioning

confidence: 99%

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Core-Binding Factor Subunit Beta Is Not Required for Non-Primate Lentiviral Vif-Mediated APOBEC3 Degradation

Zhu

Wang

et al. 2014

J Virol

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“…The infectious molecular clone pNL4-3 and the Vif mutant pNL4-3⌬Vif construct were obtained from the National Institutes of Health AIDS Research and Reference Reagents Program (NIH-ARRRP), Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID). VR1012, A3G fused to hemagglutinin (HA) tag (A3G-HA), A3C-HA, A3F-V5, African green monkey (AGM) A3G-HA, feline A3Z3-HA ([fA3Z3-HA] where A3Z3 is the A3 protein with a Z3 domain), pHIV-1 Vif-cmyc, Vif-HA, SIVagmTan Vif-cmyc (where SIVagmTan is simian immunodeficiency virus isolated from tantalus African green monkeys), feline immunodeficiency virus (FIV) Vif-cmyc, Cullin5-HA, and ElonginC-HA have been previously described (33,34,61,67,68,71,72). A polycistronic expression vector, pST39 (57), was used to express the ElonginB/C complex in Escherichia coli.…”

Section: Methodsmentioning

confidence: 99%

Small-Molecule Inhibition of Human Immunodeficiency Virus Type 1 Replication by Targeting the Interaction between Vif and ElonginC

Zuo

Liu

et al. 2012

J Virol

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The HIV-1 viral infectivity factor (Vif) protein is essential for viral replication. Vif recruits cellular ElonginB/C-Cullin5 E3 ubiquitin ligase to target the host antiviral protein APOBEC3G (A3G) for proteasomal degradation. In the absence of Vif, A3G is packaged into budding HIV-1 virions and introduces multiple mutations in the newly synthesized minus-strand viral DNA to restrict virus replication. Thus, the A3G-Vif-E3 complex represents an attractive target for development of novel anti-HIV drugs. In this study, we identified a potent small molecular compound (VEC-5) by virtual screening and validated its anti-Vif activity through biochemical analysis. We show that VEC-5 inhibits virus replication only in A3G-positive cells. Treatment with VEC-5 increased cellular A3G levels when Vif was coexpressed and enhanced A3G incorporation into HIV-1 virions to reduce viral infectivity. Coimmunoprecipitation and computational analysis further attributed the anti-Vif activity of VEC-5 to the inhibition of Vif from direct binding to the ElonginC protein. These findings support the notion that suppressing Vif function can liberate A3G to carry out its antiviral activity and demonstrate that regulation of the Vif-ElonginC interaction is a novel target for small-molecule inhibitors of HIV-1.

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“…Additionally, Ai et al (2014) have shown that the conserved CBF-b interaction sequences in SIV/HIV Vif are not present in FIV Vif. Furthermore, Wang et al (2011) have reported that the FIV Vif has neither a CUL5 box nor HCCH zincbinding motif, despite a functional requirement for CUL5 in APOBEC3 degradation. Due to these extensive differences with primate lentiviral Vif proteins, it is not clear whether FIV Vif has adapted to use another cellular protein(s) or whether it is capable of functioning without a CBF-b-like co-factor.…”

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confidence: 99%

Vif determines the requirement for CBF-β in APOBEC3 degradation

Yoshikawa

Takeuchi

Yamada

et al. 2015

Journal of General Virology

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APOBEC3 (apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3) proteins are cellular DNA deaminases that restrict a broad spectrum of lentiviruses. This process is counteracted by Vif (viral infectivity factor) of lentiviruses, which binds APOBEC3s and promotes their degradation. CBF-b (core binding factor subunit b) is an essential co-factor for the function of human immunodeficiency virus type 1 Vif to degrade human APOBEC3s. However, the requirement for CBF-b in Vif-mediated degradation of other mammalian APOBEC3 proteins is less clear. Here, we determined the sequence of feline CBFB and performed phylogenetic analyses. These analyses revealed that mammalian CBFB is under purifying selection. Moreover, we demonstrated that CBF-b is dispensable for feline immunodeficiency virus Vif-mediated degradation of APOBEC3s of its host. These findings suggested that primate lentiviruses have adapted to use CBF-b, an evolutionary stable protein, to counteract APOBEC3 proteins of their hosts after diverging from other lentiviruses.

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Identification of a Cullin5-ElonginB-ElonginC E3 Complex in Degradation of Feline Immunodeficiency Virus Vif-Mediated Feline APOBEC3 Proteins

Cited by 30 publications

References 64 publications

Core-Binding Factor Subunit Beta Is Not Required for Non-Primate Lentiviral Vif-Mediated APOBEC3 Degradation

Core-Binding Factor Subunit Beta Is Not Required for Non-Primate Lentiviral Vif-Mediated APOBEC3 Degradation

Small-Molecule Inhibition of Human Immunodeficiency Virus Type 1 Replication by Targeting the Interaction between Vif and ElonginC

Vif determines the requirement for CBF-β in APOBEC3 degradation

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