Protein Inhibitor of Activated STAT2 Restricts HCV Replication by Modulating Viral Proteins Degradation

Guo, Jing; Chen, Dan; Gao, Xiaoxiao; Zhou, Yuan; Wu, Chunchen; Wang, Yun; Chen, Jizheng; Pei, Rongjuan; Chen, Xinwen

doi:10.3390/v9100285

Cited by 14 publications

(10 citation statements)

References 50 publications

(55 reference statements)

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“…Previous studies suggest that members of the H . sapiens PIAS family of E3 ligases, which are primarily known for their role as negative regulators of innate immunity, also possess intrinsic immune functions to suppress viral replication in mammalian cells [ 59 – 61 ]. In Ae .…”

Section: Discussionmentioning

confidence: 99%

“…Such differences PLOS PATHOGENS may be linked to virus-specific requirements for component proteins of the AaSUMOylation pathway to restrict arbovirus replication. Previous studies suggest that members of the H. sapiens PIAS family of E3 ligases, which are primarily known for their role as negative regulators of innate immunity, also possess intrinsic immune functions to suppress viral replication in mammalian cells [59][60][61]. In Ae.…”

Section: Plos Pathogensmentioning

confidence: 99%

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The SUMOylation pathway suppresses arbovirus replication in Aedes aegypti cells

et al. 2020

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Mosquitoes are responsible for the transmission of many clinically important arboviruses that cause significant levels of annual mortality and socioeconomic health burden worldwide. Deciphering the mechanisms by which mosquitoes modulate arbovirus infection is crucial to understand how viral-host interactions promote vector transmission and human disease. SUMOylation is a post-translational modification that leads to the covalent attachment of the Small Ubiquitin-like MOdifier (SUMO) protein to host factors, which in turn can modulate their stability, interaction networks, sub-cellular localisation, and biochemical function. While the SUMOylation pathway is known to play a key role in the regulation of host immune defences to virus infection in humans, the importance of this pathway during arbovirus infection in mosquito vectors, such as Aedes aegypti (Ae. aegypti), remains unknown. Here we characterise the sequence, structure, biochemical properties, and tissue-specific expression profiles of component proteins of the Ae. aegypti SUMOylation pathway. We demonstrate significant biochemical differences between Ae. aegypti and Homo sapiens SUMOylation pathways and identify cell-type specific patterns of SUMO expression in Ae. aegypti tissues known to support arbovirus replication. Importantly, depletion of core SUMOylation effector proteins (SUMO, Ubc9 and PIAS) in Ae. aegypti cells led to enhanced levels of arbovirus replication from three different families; Zika (Flaviviridae), Semliki Forest (Togaviridae), and Bunyamwera (Bunyaviridae) viruses. Our findings identify an important role for mosquito SUMOylation in the cellular restriction of arboviruses that may directly influence vector competence and transmission of clinically important arboviruses.

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Section: Discussionmentioning

confidence: 99%

Section: Plos Pathogensmentioning

confidence: 99%

The SUMOylation pathway suppresses arbovirus replication in Aedes aegypti cells

et al. 2020

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“…In contrast to the essential role of SUMO1 and Ubc9 in HCV replication, PIAS2-mediated SUMOylation has been identified as a restriction factor against HCV replication [93]. Thus, an enhancement of HCV core, NS3, and NS5A protein expression in infected cells, as well as of viral assembly and budding efficiency, was observed after knockdown of PIAS2 [93]. In contrast, exogenous overexpression of PIAS2 decreased HCV core, NS3, and NS5A expression and the viral assembly and budding efficiency.…”

Section: Flaviviridaementioning

confidence: 99%

“…When expressed together with SUMO1, PIAS2 induced the degradation of HCV core, NS3, and NS5A proteins expressed from individual plasmids and after treatment with the proteasome inhibitor MG132, PIAS2 interacts with and enhances SUMOylation of the core protein. Therefore, PIAS2 has been proposed to mediate the degradation of the core, NS5A, and NS3 proteins through a ubiquitin-independent proteasomal pathway [93].…”

Section: Flaviviridaementioning

confidence: 99%

SUMO and Cytoplasmic RNA Viruses: From Enemies to Best Friends

Motiam

Vidal

Seoane

et al. 2020

Advances in Experimental Medicine and Biology

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SUMO is a ubiquitin-like protein that covalently binds to lysine residues of target proteins and regulates many biological processes such as protein subcellular localization or stability, transcription, DNA repair, innate immunity, or antiviral defense. SUMO has a critical role in the signaling pathway governing type I interferon (IFN) production, and among the SUMOylation substrates are many IFN-induced proteins. The overall effect of IFN is increasing global SUMOylation, pointing to SUMO as part of the antiviral stress response. Viral agents have developed different mechanisms to counteract the antiviral activities exerted by SUMO, and some viruses have evolved to exploit the host SUMOylation machinery to modify their own proteins. The exploitation of SUMO has been mainly linked to nuclear replicating viruses due to the predominant nuclear localization of SUMO proteins and enzymes involved in SUMOylation. However, SUMOylation of numerous viral proteins encoded by RNA viruses replicating at the cytoplasm has been lately described. Whether nuclear localization of these viral proteins is required for their SUMOylation is unclear. Here, we summarize the studies on exploitation of SUMOylation by cytoplasmic RNA viruses and discuss about the requirement for nuclear localization of their proteins. Keywords SUMO · RNA viruses · Interferon SUMO ConjugationSUMOylation consists in the covalent attachment of the small ubiquitin-like modifier (SUMO) proteins to specific lysine residues of a target protein. This conjugation is an enzymatic process that occurs in cascade. The precursor SUMO proteins are proteolytically processed to the

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“…As expected, how PIAS2 regulates viral replication mainly depends on where the SUMOylated substrates end up. PIAS2 SUMOylated core protein of Hepatitis C virus (HCV) can degrade core proteins, thereby inhibiting HCV replication (Guo et al, 2017). PIAS2α interacts with NP of the WSN H1N1 to promote NP SUMOylation, which ensures the normal trafficking of NP in mammal cells (Han et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Duck PIAS2 Promotes H5N1 Avian Influenza Virus Replication Through Its SUMO E3 Ligase Activity

Xue

et al. 2020

Front. Microbiol.

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The protein inhibitor of the activated STAT2 (PIAS2) has been implicated in many cellular processes and can also regulate viral replication in mammals. However, the role of PIAS2 in the highly pathogenic avian influenza virus (HPAIV) H5N1 replication in ducks is still unclear. Through liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay, we identified that duck PIAS2 (duPIAS2) was one protein that interacted with the nucleoprotein (NP) from the H5N1 HPAIV strain of DK212. Through confocal microscopy images and Co-IP assay, we confirmed NP could interact with duPIAS2. Overexpression of duPIAS2 in primary duck embryo fibroblast (DEF) cells was shown to promote DK212 replication, and knockdown of duPIAS2 could repress DK212 replication. We further found duPIAS2 could promote NP SUMOylation through duck SUMO1 (duSUMO1), and the potential SUMOylation sites of NP were at lysines 7, 48, and 87. Furthermore, duPIAS2 promoted the replication of DK212, here relying on the activity of its SUMO E3 ligase. Duck SENP1 (duSENP1), a deSUMOylation enzyme, could repress NP SUMOylation and also inhibit DK212 replication. Together, we identified duPIAS2 could interact with NP and that duPIAS2 promoted H5N1 HPAIV replication, which might be related to NP SUMOylation.

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Protein Inhibitor of Activated STAT2 Restricts HCV Replication by Modulating Viral Proteins Degradation

Cited by 14 publications

References 50 publications

The SUMOylation pathway suppresses arbovirus replication in Aedes aegypti cells

The SUMOylation pathway suppresses arbovirus replication in Aedes aegypti cells

SUMO and Cytoplasmic RNA Viruses: From Enemies to Best Friends

Duck PIAS2 Promotes H5N1 Avian Influenza Virus Replication Through Its SUMO E3 Ligase Activity

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