IFP35 Is Involved in the Antiviral Function of Interferon by Association with the Viral Tas Transactivator of Bovine Foamy Virus

Tan, Juan; Qiao, Wentao; Wang, Jian; Xu, Feifei; Li, Yue; Zhou, Jun; Chen, Qimin; Geng, Yi

doi:10.1128/jvi.02249-07

Cited by 63 publications

(57 citation statements)

References 42 publications

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“…We have found that it is also induced by transfection of cells with poly(I·C) or by infection with SeV (data not shown). The only study reported so far suggests that IFI35 interacts with the bovine foamy virus (BFV) trans-activator protein Tas and that this interaction blocks the ability of Tas to activate viral gene transcription, resulting in inhibition of BFV replication (49). Thus, in this context, IFI35 exhibits an antiviral role and suppresses virus replication.…”

Section: Discussionmentioning

confidence: 99%

Interferon-Inducible Protein IFI35 Negatively Regulates RIG-I Antiviral Signaling and Supports Vesicular Stomatitis Virus Replication

Das

Dinh

Panda

et al. 2014

J Virol

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In a genome-wide small interfering RNA (siRNA) screen, we recently identified the interferon (IFN)-inducible protein 35 (IFI35; also known as IFP35) as a factor required for vesicular stomatitis virus (VSV) infection. Studies reported here were conducted to further understand the role and requirement of IFI35 in VSV infection. Consistent with the siRNA screening data, we found that depletion of IFI35 led to reduced VSV replication at the level of viral gene expression. Although no direct interaction of IFI35 with the viral replication machinery was observed, we found that IFI35 negatively regulated the host innate immune response and rescued poly(I·C)-induced inhibition of VSV replication. Promoter-driven reporter gene assays demonstrated that IFI35 overexpression suppressed the activation of IFN-␤ and ISG56 promoters, whereas its depletion had the opposite effect. Further investigation revealed that IFI35 specifically interacted with retinoic acid-inducible gene I (RIG-I) and negatively regulated its activation through mechanisms that included (i) suppression of dephosphorylation (activation) of RIG-I and (ii) proteasome-mediated degradation of RIG-I via K48-linked ubiquitination. Overall, the results presented here suggest a novel role for IFI35 in negative regulation of RIG-I-mediated antiviral signaling, which will have implications for diseases associated with excessive immune signaling. IMPORTANCE Mammalian cells employ a variety of mechanisms, including production of interferons (IFNs), to counteract invading pathogens. In this study, we identified a novel role for a cellular protein, IFN-inducible protein 35 (IFP35/IFI35), in negatively regulating the host IFN response during vesicular stomatitis virus (VSV) infection. Specifically, we found that IFI35 inhibited activation of the RNA sensor, the retinoic acid-inducible gene I (RIG-I), leading to inhibition of IFN production and thus resulting in better replication of VSV. The identification of a cellular factor that attenuates the IFN response will have implications toward understanding inflammatory diseases in humans that have been found to be associated with defects in the regulation of host IFN production, such as systemic lupus erythematosus and psoriasis.

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Section: Discussionmentioning

confidence: 99%

Interferon-Inducible Protein IFI35 Negatively Regulates RIG-I Antiviral Signaling and Supports Vesicular Stomatitis Virus Replication

Das

Dinh

Panda

et al. 2014

J Virol

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“…All these observations suggest that Nmi harbors antiviral activity. To date, PML, IFP35, and Nmi have been reported to inhibit FV replication through interacting with Tas (15,24). PML interacts directly with Tas and interferes with its ability to bind PFV LTR and IP (15).…”

Section: Discussionmentioning

confidence: 99%

“…For instance, apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3) proteins are known to act during FV reverse transcription (RT) and introduce lethal mutations in the viral genome (19)(20)(21)(22), whereas tetherin inhibits viral release without affecting the FV cell-to-cell spread (23). Other antiviral ISGs include promyelocytic leukemia protein (PML) and IFN-induced 35-kDa protein (IFP35) (15,24). These ISGs likely limit or modulate the viral spread in vivo, but other ISGs that can lead to FV latency remain unexplored.…”

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confidence: 99%

N-Myc Interactor Inhibits Prototype Foamy Virus by Sequestering Viral Tas Protein in the Cytoplasm

Yang

Liu

et al. 2014

J Virol

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Foamy viruses (FVs) are complex retroviruses that establish lifelong persistent infection without evident pathology. However, the roles of cellular factors in FV latency are poorly understood. This study revealed that N-Myc interactor (Nmi) could inhibit the replication of prototype foamy virus (PFV). Overexpression of Nmi reduced PFV replication, whereas its depletion by small interfering RNA increased PFV replication. The Nmi-mediated impairment of PFV replication resulted from the diminished transactivation by PFV Tas of the viral long terminal repeat (LTR) and an internal promoter (IP). Nmi was determined to interact with Tas and abrogate its function by sequestration in the cytoplasm. In addition, human and bovine Nmi proteins were found to inhibit the replication of bovine foamy virus (BFV) and PFV. Together, these results indicate that Nmi inhibits both human and bovine FVs by interfering with the transactivation function of Tas and may have a role in the host defense against FV infection. IMPORTANCEFrom this study, we report that the N-Myc interactor (Nmi), an interferon-induced protein, can interact with the regulatory protein Tas of the prototype foamy virus and sequester it in the cytoplasm. The results of this study suggest that Nmi plays an important role in maintaining foamy virus latency and may reveal a new pathway in the interferon-mediated antiviral barrier against viruses. These findings are important for understanding virus-host relationships not only with FVs but potentially for other retroviruses as well.

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“…It interacts with the bovine foamy virus Tas regulatory protein, and its overexpression disturbs viral gene transcription and replication of the bovine foamy virus Tas protein. Furthermore, IFP35 plays a crucial role in the interferon-induced anti-foamy virus host response (Tan et al, 2008). First discovered by Lohman andMayerhof in 1934 (Lohman et al, 1934), α-enolase was later shown to be a highly conserved enzyme that catalyses the transformation of 2-phosphoglyceric acid to enolphosphopyruvate in the Embden-Meyerhof-Parnas pathway (Wold, 1971).…”

Section: Tasmentioning

confidence: 99%

Development of Foamy Virus Vectors for Gene Therapy for Neurological Disorders and Other Diseases

Zhang¹,

Zhu²,

Yu³

et al. 2012

Advanced Topics in Neurological Disorders

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IFP35 Is Involved in the Antiviral Function of Interferon by Association with the Viral Tas Transactivator of Bovine Foamy Virus

Cited by 63 publications

References 42 publications

Interferon-Inducible Protein IFI35 Negatively Regulates RIG-I Antiviral Signaling and Supports Vesicular Stomatitis Virus Replication

Interferon-Inducible Protein IFI35 Negatively Regulates RIG-I Antiviral Signaling and Supports Vesicular Stomatitis Virus Replication

N-Myc Interactor Inhibits Prototype Foamy Virus by Sequestering Viral Tas Protein in the Cytoplasm

Development of Foamy Virus Vectors for Gene Therapy for Neurological Disorders and Other Diseases

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