Poxviruses and paramyxoviruses use a conserved mechanism of STAT1 antagonism to inhibit interferon signaling

Talbot-Cooper, Callum; Pantelejevs, Teodors; Shannon, James A.; Cherry, Christian R.; Au, Marcus; Hyvönen, Marko; Hickman, Heather D.; Smith, Geoffrey L.

doi:10.1016/j.chom.2022.01.014

Cited by 16 publications

(6 citation statements)

References 91 publications

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“…These transcription factors induce the expression of type I interferon (IFN-I), and, subsequently, secreted IFN-I binds to the IFN receptor, activating the downstream expression of IFN-stimulated genes (ISGs) [34][35][36]. However, viruses must counter IFN's powerful responses by regulating or evading these defenses to facilitate viral infection [37]. Notably, previous studies revealed that PRRSV is susceptible to the antiviral acticity of IFNs both in vivo and in vitro [38].…”

Section: Discussionmentioning

confidence: 99%

Innate Immune Evasion of PRRSV nsp11 through Degradation of the HDAC2 by Its Endoribonuclease Activity

Zhang,

Chen,

et al. 2024

Viruses

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Porcine reproductive and respiratory syndrome virus (PRRSV), a member of the Arteriviridae family, represents a persistent menace to the global pig industry, causing reproductive failure and respiratory disease in pigs. In this study, we delved into the role of histone deacetylases (HDAC2) during PRRSV infection. Our findings revealed that HDAC2 expression is downregulated upon PRRSV infection. Notably, suppressing HDAC2 activity through specific small interfering RNA led to an increase in virus production, whereas overexpressing HDAC2 effectively inhibited PRRSV replication by boosting the expression of IFN-regulated antiviral molecules. Furthermore, we identified the virus’s nonstructural protein 11 (nsp11) as a key player in reducing HDAC2 levels. Mutagenic analyses of PRRSV nsp11 revealed that its antagonistic effect on the antiviral activity of HDAC2 is dependent on its endonuclease activity. In summary, our research uncovered a novel immune evasion mechanism employed by PRRSV, providing crucial insights into the pathogenesis of this virus and guiding the development of innovative prevention strategies against PRRSV infection.

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Section: Discussionmentioning

confidence: 99%

Innate Immune Evasion of PRRSV nsp11 through Degradation of the HDAC2 by Its Endoribonuclease Activity

Zhang,

Chen,

et al. 2024

Viruses

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“…The ability of B12 to enhance DNA induced signaling contrasts with the inhibition of innate immune signaling by many other immunomodulatory VACV proteins ( 84 ). VACV blocks the sensing of cytosolic PAMPs (e.g., cytosolic dsDNA) ( 50 , 85 – 87 ), the signaling cascades that activate IFN production ( 52 , 53 , 88 , 89 ), type I IFN signaling ( 54 , 90 , 91 ), and the actions of ISGs ( 92 , 93 ). However, the finding that a pathogen-encoded protein results in augmentation of innate immune signaling is not unique ( 94 ) and emphasizes the complexity of the cross-regulatory immunity networks of the host ( 95 , 96 ).…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of Cellular VRK1, BAF, and Innate Immune Signaling by the Vaccinia Virus B12 Pseudokinase

Linville

Rico

Teague

et al. 2022

J Virol

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“…Specific host proteins are affected by MPXV utilising host-synthesized proteins and affecting immune system responses. For example, cytokines [interleukin 1 (IL-1)] and type I/II interferons (IFNs) are known to be affected by OPXVs due to protein homology and comparative knowledge of IFN signaling [72][73][74]. The role of type III IFN in OPXVs remains unclear and are therapeutic targets under investigation in other inflammatory pathologies [75,76].…”

Section: Cellular Mpox and Opxv Historical Evolution On Viral Entrymentioning

confidence: 99%

Immunopathogenesis of Orthopoxviridae: insights into immunology from smallpox to monkeypox (mpox)

Brown,

Fricke,

Imarogbe

et al. 2023

Explor Immunol

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Since 2019, notable global viral outbreaks have occurred necessitating further research and healthcare system investigations. Following the coronavirus disease 2019 (COVID-19) pandemic, in 2022, whilst severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains evolved, monkeypox virus (MPXV) infections became more evident. MPXV is of the Orthopoxviridae genus, belonging to the family Poxviridae. Zoonotic transmission (animal-to-human transmission) may occur. The Orthopoxviridae genus includes other orthopoxviruses (OPXVs) present in animal host reservoirs that include cowpox viruses (CPXVs), vaccinia virus (VACV), and variola virus (VARV), with the latter being a causal agent of smallpox and excessive mortality. This review aims to present facts about MPXV-specific pathogenesis, epidemiology, and immunology alongside historical perspectives. MPXV was rarely reported outside Africa before April 2000. Early research since 1796 contributed towards the eradication of VARV leading to immunisation strategies. The World Health Organisation (WHO) announcement that VARV had been eradicated was confirmed in 1980. On the 23rd of July 2022, the WHO announced MPXV as a health emergency. Therefore, concern due to the propagation of MPXV causing monkeypox (mpox) disease requires clarity. Infected hosts display symptoms like extensive cellular-initiated rashes and lesions. Infection with MPXV makes it difficult to differentiate from other diseases or skin conditions. Antiviral therapeutic drugs were typically prescribed for smallpox and mpox disease; however, the molecular and immunological mechanisms with cellular changes remain of interest. Furthermore, no official authorized treatment exists for mpox disease. Some humans across the globe may be considered at risk. Historically, presenting symptoms of mpox resemble other viral diseases. Symptoms include rashes or lesions like Streptococcus, but also human herpes viruses (HHVs), including Varicella zoster virus (VZV).

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Poxviruses and paramyxoviruses use a conserved mechanism of STAT1 antagonism to inhibit interferon signaling

Cited by 16 publications

References 91 publications

Innate Immune Evasion of PRRSV nsp11 through Degradation of the HDAC2 by Its Endoribonuclease Activity

Innate Immune Evasion of PRRSV nsp11 through Degradation of the HDAC2 by Its Endoribonuclease Activity

Dysregulation of Cellular VRK1, BAF, and Innate Immune Signaling by the Vaccinia Virus B12 Pseudokinase

Immunopathogenesis of Orthopoxviridae: insights into immunology from smallpox to monkeypox (mpox)

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