Mumps Virus SH Protein Inhibits NF-κB Activation by Interacting with Tumor Necrosis Factor Receptor 1, Interleukin-1 Receptor 1, and Toll-Like Receptor 3 Complexes

Franz, Stephanie; Rennert, Paul D.; Woznik, Maria; Grützke, Josephine; Lüdde, Amy; Pais, Eva Maria Arriero; Finsterbusch, Tim; Geyer, Henriette; Mankertz, Annette; Friedrich, Nicole

doi:10.1128/jvi.01037-17

Cited by 27 publications

(20 citation statements)

References 55 publications

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“…Deletion of the SH protein of these viruses did not affect replication and gene expression in vitro (12,14,16,21). Recently, it was reported that MuV SH inhibits TNF-␣, interleukin-1␤ (IL-1␤), and NF-B activation by interacting with TNF receptor 1 (TNF-R1), IL-1 receptor 1 (IL-1R1), and Toll-like receptor 3 (TLR3) complexes (28). These findings suggest the role of SH in evading the host immune response.…”

Section: Discussionmentioning

confidence: 99%

Role of Small Hydrophobic Protein of J Paramyxovirus in Virulence

Abraham

Arroyo-Diaz

et al. 2018

J Virol

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J paramyxovirus (JPV) was first isolated from moribund mice with hemorrhagic lung lesions in Australia in 1972. It is a paramyxovirus classified under the newly proposed genus JPV has a genome of 18,954 nucleotides, consisting of eight genes in the order 3'-N-P/V/C-M-F-SH-TM-G-L-5'. JPV causes little cytopathic effect (CPE) in tissue culture cells but severe disease in mice. The small hydrophobic (SH) protein is an integral membrane protein encoded by many paramyxoviruses, such as mumps virus (MuV) and respiratory syncytial virus (RSV). However, the function of SH has not been defined in a suitable animal model. In this work, the functions of SH of JPV, MuV, and RSV have been examined by generating recombinant JPV lacking the SH protein (rJPV-ΔSH) or replacing SH of JPV with MuV SH (rJPV-MuVSH) or RSV SH (rJPV-RSVSH). rJPV-ΔSH, rJPV-MuVSH, and rJPV-RSVSH were viable and had no growth defect in tissue culture cells. However, more tumor necrosis factor alpha (TNF-α) was produced during rJPV-ΔSH infection, confirming the role of SH in inhibiting TNF-α production. rJPV-ΔSH induced more apoptosis in tissue culture cells than rJPV, rJPV-MuVSH, and rJPV-RSVSH, suggesting that SH plays a role in blocking apoptosis. Furthermore, rJPV-ΔSH was attenuated in mice compared to rJPV, rJPV-MuVSH, and rJPV-RSVSH, indicating that the SH protein plays an essential role in virulence. The results indicate that the functions of MuV SH and RSV SH are similar to that of JPV SH even though they have no sequence homology. Paramyxoviruses are associated with many devastating diseases in animals and humans. J paramyxovirus (JPV) was isolated from moribund mice in Australia in 1972. Newly isolated viruses, such as Beilong virus (BeiPV) and Tailam virus (TlmPV), have genome structures similar to that of JPV. A new paramyxovirus genus, , which contains JPV, BeiPV, and TlmPV, has been proposed. Small hydrophobic (SH) protein is present in many paramyxoviruses. Our present study investigates the role of SH protein of JPV in pathogenesis in its natural host. Understanding the pathogenic mechanism of is important to control and prevent potential diseases that may emerge from this group of viruses.

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Section: Discussionmentioning

confidence: 99%

Role of Small Hydrophobic Protein of J Paramyxovirus in Virulence

Abraham

Arroyo-Diaz

et al. 2018

J Virol

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“…HSV1 UL24 binds to NF‐κB subunits p65 and p50 and abrogates nuclear translocation during disease, decreasing NF‐κB activity via the cGAS‐STING response 100. Mumps virus (MuV) small hydrophobic protein (SH) decreases NF‐κB stimulation by reducing inhibitor of kappa B (IκB) kinase α (IKKα) and kinase β (IKKβ), and p65 phosphorylation, including nuclear translocation of p65 in diseased cells 101. HSV1 UL36USP deubiquitinates IκBα and restricts its degradation, subsequently preventing NF‐κB activation during viral infection 102.…”

Section: Regulation Of Innate Immune Responsesmentioning

confidence: 99%

Regulation of cGAS‐Mediated Immune Responses and Immunotherapy

et al. 2020

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Early detection of infectious nucleic acids released from invading pathogens by the innate immune system is critical for immune defense. Detection of these nucleic acids by host immune sensors and regulation of DNA sensing pathways have been significant interests in the past years. Here, current understandings of evolutionarily conserved DNA sensing cyclic GMP‐AMP (cGAMP) synthase (cGAS) are highlighted. Precise activation and tight regulation of cGAS are vital in appropriate innate immune responses, senescence, tumorigenesis and immunotherapy, and autoimmunity. Hence, substantial insights into cytosolic DNA sensing and immunotherapy of indispensable cytosolic sensors have been detailed to extend limited knowledge available thus far. This Review offers a critical, in‐depth understanding of cGAS regulation, cytosolic DNA sensing, and currently established therapeutic approaches of essential cytosolic immune agents for improved human health.

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“…Some viruses suppress NF-κB activation to dampen the host immune responses to maintain latency [13] . For example, human bocavirus (HBoV) proteins NS1 and NS1-70 [14] , the mumps virus (MuV) small hydrophobic protein (SH) [15] and Molluscum contagiosum virus (MCV) protein MC005 [16] inhibit TNF-α-mediated activation of NF-κB by reducing the phosphorylation of IKKβ, IκBα, and p65 as well as the translocation of p65 into the nucleus. Some pathogenic microorganisms activate NF-κB for viral gene expression, replication and spread.…”

Section: Introductionmentioning

confidence: 99%

Different subtypes of influenza A viruses target different human proteins and pathways leading to different pathogenic phenotypes

Wang

Song

et al. 2019

Preprint

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10Different subtypes of Influenza A viruses cause different pathogenic phenotypes 11 after infecting human bodies. Direct binary interactions between viral proteins and 12 human proteins provide an important background for influenza viruses to cause complex 13 pathologies of hosts. Here, we demonstrated the different impacts on the TNF-α-induced 14 NF-κB activation of H1N1 and H5N1 virus proteins. By further examining the virus-host 15 protein-protein interactions (PPI), we found that the same segment protein of the H1N1 16 and H5N1 viruses target on different host proteins. We then performed a yeast 17 two-hybrid analysis of a highly pathogenic avian H5N1 influenza virus and human 18 proteins. Influenza-host protein-protein interaction networks of three strains of 19 influenza A viruses (including two other reported influenza-host PPI networks) were 20 systematically compared and mapped on the network level and the pathway level. The 21 results show subtype-specific characters of the influenza-host protein interactome, 22 which may response for the specific pathogenic mechanisms of different subtypes of 23 influenza viruses. 24 Importance 25 Influenza A virus (IAV) can cause contagious respiratory illness, namely influenza (flu). 26 The symptoms of infections from different subtypes of IAVs vary from mild to severe 27 illness. The mechanism of these different pathogenic phenotypes remains poorly 28 understood. Our results show that the same NA and NP segments from H1N1 and H5N1 29 virus cause different impacts on the TNF-α-induced NF-κB pathway. Furthermore, we 30 generated a yeast two-hybrid protein-protein interaction (PPI) network between H5N1 31 and human proteins. By systematically comparing the influenza-host PPI networks of 32 three strains of IAVs, we show that different subtypes of IAVs target different human 33 proteins and pathways, which may have led to different pathogenic phenotypes. 34 51 According to the monitoring report from WHO, H5N1 AIVs have resulted in 860 human 52 infections and 453 deaths as of November 1, 2018 [15]. Constantly reported sporadic 53 human infectious with H5N1 and its high mortality warn us that H5N1 AIV may cause 54 serious epidemic worldwide. It is necessary to improve the epidemiological surveillance 55 and the research of pathogenic mechanism on these important subtypes of influenza 56 viruses. 57 Both H1N1 and H5N1 influenza viruses have posed tremendous health threats in 58 many regions worldwide, but their transmissibility, virulence and fatality are quite 59 different [16]. Although characterized by high transmissibility, the virulence and fatality 60 of the H1N1 influenza virus are relatively low. The reverse holds true for H5N1 influenza. 61 With a fatality rate that exceeds 60%, it is known to cause severe damage to the human 62 respiratory system, but the virus is not presently capable of efficient transmission from 63 human to human. 64 An important step to understand the pathogenesis of the pathogens is to 65 investigate the protein-protein interactio...

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Mumps Virus SH Protein Inhibits NF-κB Activation by Interacting with Tumor Necrosis Factor Receptor 1, Interleukin-1 Receptor 1, and Toll-Like Receptor 3 Complexes

Cited by 27 publications

References 55 publications

Role of Small Hydrophobic Protein of J Paramyxovirus in Virulence

Role of Small Hydrophobic Protein of J Paramyxovirus in Virulence

Regulation of cGAS‐Mediated Immune Responses and Immunotherapy

Different subtypes of influenza A viruses target different human proteins and pathways leading to different pathogenic phenotypes

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