Structural homology screens reveal host-derived poxvirus protein families impacting inflammasome activity

Boys, Ian N.; Johnson, Alex G.; Quinlan, Meghan; Kranzusch, Philip J.; Elde, Nels C.

doi:10.1016/j.celrep.2023.112878

Cited by 6 publications

(15 citation statements)

References 73 publications

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“…In addition to eukaryotic and prokaryotic cells, GSDM homologs have also been found in viruses. A recent study identified vaccinia virus (VACV) A47 as a homolog of GSDMs through structural modeling, which was further confirmed by an X-ray crystal structure of A47 ( 19 ). The authors conducted a structural homology screen for VACV, eliminating most nonspecific results and yielding 60 well-characterized homologs of host proteins, including A47.…”

Section: Gsdm Homologs In Virusesmentioning

confidence: 80%

“…The authors conducted a structural homology screen for VACV, eliminating most nonspecific results and yielding 60 well-characterized homologs of host proteins, including A47. In this study, AlphaFold2 ( 41 ) was utilized to demonstrate that eptesipox GSDM shows significant structural homology with various metazoan GSDM CTDs and the predicted AlphaFold2 model of VACV A47 ( 19 ). However, eptesipox GSDM possesses an additional α-helix off its N terminus that is not present in metazoan GSDMs ( 19 ).…”

Section: Gsdm Homologs In Virusesmentioning

confidence: 99%

“…In this study, AlphaFold2 ( 41 ) was utilized to demonstrate that eptesipox GSDM shows significant structural homology with various metazoan GSDM CTDs and the predicted AlphaFold2 model of VACV A47 ( 19 ). However, eptesipox GSDM possesses an additional α-helix off its N terminus that is not present in metazoan GSDMs ( 19 ).…”

Section: Gsdm Homologs In Virusesmentioning

confidence: 99%

“…The release of specific cytokines through these pores includes the proinflammatory cytokines interleukin (IL)-1β and IL-18, which exert toxic effects on the surrounding cells and tissues ( 14 ). Recent studies have uncovered the presence of GSDM-containing immune systems in microorganisms such as Bradyrhizobium tropiciagri , Vitiosangium sp., Runella , Podospora anserina , Neurospora crassa , and poxviruses ( 16 – 19 ). GSDMs from microorganisms exhibit structural similarities to those found in host cells, but they may induce different biological behaviors.…”

Section: Introductionmentioning

confidence: 99%

“…However, viruses possess the ability to continually evolve and acquire host genes to manipulate host biology, facilitating their replication ( 22 ). A recent study demonstrated that a GSDM homolog present in poxvirus can interfere with inflammatory caspases, suppressing inflammasome signaling and pyroptosis ( 19 ). This finding highlights the dual role of GSDM homologs in immunological processes across different species and their involvement in viral infections.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Evolutionary insights and functional diversity of gasdermin family proteins and homologs in microorganisms

Wang,

Ma,

Xia

et al. 2024

Front. Immunol.

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The gasdermin protein family and its homologs in microorganisms have gained significant attention due to their roles in programmed cell death, immune defense, and microbial infection. This review summarizes the current research status of gasdermin proteins, their structural features, and functional roles in fungi, bacteria, and viruses. The review presents evolutionary parallels between mammalian and microbial defense systems, highlighting the conserved role of gasdermin proteins in regulating cell death processes and immunity. Additionally, the structural and functional characteristics of gasdermin homologs in microorganisms are summarized, shedding light on their potential as targets for therapeutic interventions. Future research directions in this field are also discussed to provide a roadmap for further investigation.

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Section: Gsdm Homologs In Virusesmentioning

confidence: 80%

Section: Gsdm Homologs In Virusesmentioning

confidence: 99%

Section: Gsdm Homologs In Virusesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Evolutionary insights and functional diversity of gasdermin family proteins and homologs in microorganisms

Wang,

Ma,

Xia

et al. 2024

Front. Immunol.

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The monkeypox virus-host interplays

Yi,

Lei,

et al. 2024

Cell Insight

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Quantitative proteomics defines mechanisms of antiviral defence and cell death during modified vaccinia Ankara infection

Albarnaz,

Kite,

Oliveira

et al. 2023

Nat Commun

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Modified vaccinia Ankara (MVA) virus does not replicate in human cells and is the vaccine deployed to curb the current outbreak of mpox. Here, we conduct a multiplexed proteomic analysis to quantify >9000 cellular and ~80% of viral proteins throughout MVA infection of human fibroblasts and macrophages. >690 human proteins are down-regulated >2-fold by MVA, revealing a substantial remodelling of the host proteome. >25% of these MVA targets are not shared with replication-competent vaccinia. Viral intermediate/late gene expression is necessary for MVA antagonism of innate immunity, and suppression of interferon effectors such as ISG20 potentiates virus gene expression. Proteomic changes specific to infection of macrophages indicate modulation of the inflammatory response, including inflammasome activation. Our approach thus provides a global view of the impact of MVA on the human proteome and identifies mechanisms that may underpin its abortive infection. These discoveries will prove vital to design future generations of vaccines.

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Structural homology screens reveal host-derived poxvirus protein families impacting inflammasome activity

Cited by 6 publications

References 73 publications

Evolutionary insights and functional diversity of gasdermin family proteins and homologs in microorganisms

Evolutionary insights and functional diversity of gasdermin family proteins and homologs in microorganisms

The monkeypox virus-host interplays

Quantitative proteomics defines mechanisms of antiviral defence and cell death during modified vaccinia Ankara infection

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