Feline Immunodeficiency Virus Vif N-Terminal Residues Selectively Counteract Feline APOBEC3s

Gu, Qinyong; Zhang, Zeli; Cano-Ortiz, Lucía; Franco, Ana Cláudia; Häussinger, Dieter; Münk, Carsten

doi:10.1128/jvi.01593-16

Cited by 8 publications

(13 citation statements)

References 81 publications

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“…The results showed that FIV Vif efficiently degraded all three tested feline A3s (Felis catus A3Z2b [FcaA3Z2b], FcaA3Z3, and FcaA3Z2bZ3) in the absence of DN-CUL5 ( Fig. 1B), which is consistent with data from previous studies (4,11,14). The presence of DN-CUL5 enhanced the cellular protein level of Vif and abolished the degradation of the A3s (Fig.…”

supporting

confidence: 91%

“…Feline CUL5 and human CUL5 differ in only one amino acid, and this mutation does not affect its interaction with FIV Vif (18). It was also shown that FIV Vif can induce the degradation of feline A3s in both feline kidney CRFK and HEK293T cells, thus supporting that FIV Vif can interact with human and feline CUL5 proteins (11,18). In this study, we first identified that three FIV Vif N-terminal mutants (53FI54, 57LR58, and 77VRE79) partially lost CUL5 binding, compared to wild-type FIV Vif (Fig.…”

Section: Discussionmentioning

confidence: 90%

“…FIV Vif interacts with CUL5, ELOB, and ELOC to form an E3 complex to induce the degradation of feline A3s (18). The properties of the interaction of FIV Vif with feline A3s and ELOB/C were previously identified (9,11,18). However, the interface between FIV Vif and CUL5 was not characterized.…”

Section: Discussionmentioning

confidence: 99%

“…The FIV 34TF10 (codon-optimized) Vif gene was inserted into pcWPRE containing a C-terminal V5 tag (4,9). All the FIV Vif mutants were produced by fusion PCR and inserted into pcWPRE by using EcoRI and NotI restriction sites (11). The HIV-1 Vif expression plasmid with a C-terminal V5 tag was described previously (4).…”

Section: Methodsmentioning

confidence: 99%

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Identification of a Conserved Interface of Human Immunodeficiency Virus Type 1 and Feline Immunodeficiency Virus Vifs with Cullin 5

Zhang

Gertzen

et al. 2018

J Virol

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Members of the apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC3 [A3]) family of DNA cytidine deaminases are intrinsic restriction factors against retroviruses. In felids such as the domestic cat (), the A3 genes encode the A3Z2, A3Z3, and A3Z2Z3 antiviral cytidine deaminases. Only A3Z3 and A3Z2Z3 inhibit viral infectivity factor (Vif)-deficient feline immunodeficiency virus (FIV). The FIV Vif protein interacts with Cullin (CUL), Elongin B (ELOB), and Elongin C (ELOC) to form an E3 ubiquitination complex to induce the degradation of feline A3s. However, the functional domains in FIV Vif for the interaction with Cullin are poorly understood. Here, we found that the expression of dominant negative CUL5 prevented the degradation of feline A3s by FIV Vif, while dominant negative CUL2 had no influence on the degradation of A3. In coimmunoprecipitation assays, FIV Vif bound to CUL5 but not CUL2. To identify the CUL5 interaction site in FIV Vif, the conserved amino acids from positions 47 to 160 of FIV Vif were mutated, but these mutations did not impair the binding of Vif to CUL5. By focusing on a potential zinc-binding motif (K175-C161-C184-C187) of FIV Vif, we found a conserved hydrophobic region (174IR175) that is important for the CUL5 interaction. Mutation of this region also impaired the FIV Vif-induced degradation of feline A3s. Based on a structural model of the FIV Vif-CUL5 interaction, the 52LW53 region in CUL5 was identified as mediating binding to FIV Vif. By comparing our results to the human immunodeficiency virus type 1 (HIV-1) Vif-CUL5 interaction surface (120IR121, a hydrophobic region that is localized in the zinc-binding motif), we suggest that the CUL5 interaction surface in the diverse HIV-1 and FIV Vifs is evolutionarily conserved, indicating a strong structural constraint. However, the FIV Vif-CUL5 interaction is zinc independent, which contrasts with the zinc dependence of HIV-1 Vif. Feline immunodeficiency virus (FIV), which is similar to human immunodeficiency virus type 1 (HIV-1), replicates in its natural host in T cells and macrophages that express the antiviral restriction factor APOBEC3 (A3). To escape A3s, FIV and HIV induce the degradation of these proteins by building a ubiquitin ligase complex using the viral protein Vif to connect to cellular proteins, including Cullin 5. Here, we identified the protein residues that regulate this interaction in FIV Vif and Cullin 5. While our structural model suggests that the diverse FIV and HIV-1 Vifs use conserved residues for Cullin 5 binding, FIV Vif binds Cullin 5 independently of zinc, in contrast to HIV-1 Vif.

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supporting

confidence: 91%

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Identification of a Conserved Interface of Human Immunodeficiency Virus Type 1 and Feline Immunodeficiency Virus Vifs with Cullin 5

Zhang

Gertzen

et al. 2018

J Virol

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“…Feline tetherin can prevent the release of FIV and HIV-1, which is antagonized by the FIV envelope glycoprotein [ 41 , 42 , 43 ]. Feline APOBEC3 (A3) restricts the infectivity of Vif-deficient FIV (FIVΔVif), and FIV Vif counteracts the feline A3 antiviral activity [ 44 , 45 , 46 ].…”

Section: Introductionmentioning

confidence: 99%

Feline APOBEC3s, Barriers to Cross-Species Transmission of FIV?

Zhang

Marino

et al. 2018

Viruses

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The replication of lentiviruses highly depends on host cellular factors, which defines their species-specific tropism. Cellular restriction factors that can inhibit lentiviral replication were recently identified. Feline immunodeficiency virus (FIV) was found to be sensitive to several feline cellular restriction factors, such as apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3 (APOBEC3) and tetherin, but FIV evolved to counteract them. Here, we describe the molecular mechanisms by which feline APOBEC3 restriction factors inhibit FIV replication and discuss the molecular interaction of APOBEC3 proteins with the viral antagonizing protein Vif. We speculate that feline APOBEC3 proteins could explain some of the observed FIV cross-species transmissions described in wild Felids.

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A phylogenetic study of Feline Immunodeficiency Virus (FIV) among domestic cats in Turkey

Koç

Oğuzoğlu

2020

Comparative Immunology, Microbiology and Infectious Diseases

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Feline Immunodeficiency Virus Vif N-Terminal Residues Selectively Counteract Feline APOBEC3s

Abstract: Feline immunodeficiency virus (FIV)Vif

Cited by 8 publications

References 81 publications

Identification of a Conserved Interface of Human Immunodeficiency Virus Type 1 and Feline Immunodeficiency Virus Vifs with Cullin 5

Identification of a Conserved Interface of Human Immunodeficiency Virus Type 1 and Feline Immunodeficiency Virus Vifs with Cullin 5

Feline APOBEC3s, Barriers to Cross-Species Transmission of FIV?

A phylogenetic study of Feline Immunodeficiency Virus (FIV) among domestic cats in Turkey

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