Poxvirus cGAMP nucleases: Clues and mysteries from a stolen gene

Motes, Carlos Maluquer de

doi:10.1371/journal.ppat.1009372

Cited by 15 publications

(18 citation statements)

References 25 publications

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“…Additionally, It has been sequenced and analyzed the pathogenicity family orthologs of the monkeypox virus strain ZAI-96 from Central Africa and the variola virus strain (strain BSH-75) [59]. Using the website poxvirus.org to compared the genomes of a Central African strain of monkeypox virus (strain Zaire-1979) and variola virus (strain Bangladesh-1975maj) in search of genes found in one but not the other [60]. The majority of differences between the variola and monkeypox viruses are found in ORFs with ambiguous functionality [36].…”

Section: There Are Discrepancies In the Genomes Of The Monkeypox And ...mentioning

confidence: 99%

“…Although A44L was not required for viral replication, A44L-deleted vaccinia viruses were attenuated in vivo [56]. Mice treated intranasally with the vaccinia A44L-deleted virus exhibited a robust pulmonary inflammatory response, which comprised early and rapid recruitment of lymphocytes and increased IFN-production [60]. Additionally, they recovered from an infection faster and experienced less weight loss than mice inoculated with the wild-type vaccinia virus.…”

Section: There Are Discrepancies In the Genomes Of The Monkeypox And ...mentioning

confidence: 99%

“…It is believed that A44L impacts virulence via boosting steroid synthesis, suppressing the immune system and thus altering the immunological response [58]. Unlike the variola virus, the monkeypox virus possesses an ortholog of COP-B7R consisting of 182 amino acids [60]. COP-B7R is an ER-resident protein; however, because it lacks a recognised retention signal, it is unknown how this protein is maintained [60].…”

Section: There Are Discrepancies In the Genomes Of The Monkeypox And ...mentioning

confidence: 99%

“…Unlike the variola virus, the monkeypox virus possesses an ortholog of COP-B7R consisting of 182 amino acids [60]. COP-B7R is an ER-resident protein; however, because it lacks a recognised retention signal, it is unknown how this protein is maintained [60]. When this gene is removed, it does not affect viral replication [58].…”

Section: There Are Discrepancies In the Genomes Of The Monkeypox And ...mentioning

confidence: 99%

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Monkeypox: From Past to Present Outbreak

Jeerapat¹

2022

ijcsrr

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Monkey pox is one of the most rare disease caused by the infection of monkey pox virus; the source of disease still remained unknown. It was discovered in 1958 where there is an outbreak in small-pox like disease. At that time monkey were kept to further analyze. In 1970, the first instance of monkeypox in a human was noted. Monkeypox cases have now been documented in a number of other central and western African nations. Prior to the 2022 outbreak, almost all cases of monkeypox in people outside of Africa were connected to either imported animals or foreign travel to nations where the illness frequently occurs. There are various symptoms that could be diagnosed as the monkey pox. The most common ones are the rash which is identical to pimples of blisters that appear on our face regularly. However, it may spread towards other part of our body including the hands, feet, chest, genitals, or anus. The monkey pox rash has different stages starting from the ones identical to pimples to the burned out. This illness typically last between 2-4 weeks. SInce the monkey pox disease is not as common, researchers is still currently work on discovering the root cause. In the present, there is still not enough resources available.

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Section: There Are Discrepancies In the Genomes Of The Monkeypox And ...mentioning

confidence: 99%

Section: There Are Discrepancies In the Genomes Of The Monkeypox And ...mentioning

confidence: 99%

Section: There Are Discrepancies In the Genomes Of The Monkeypox And ...mentioning

confidence: 99%

Section: There Are Discrepancies In the Genomes Of The Monkeypox And ...mentioning

confidence: 99%

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Monkeypox: From Past to Present Outbreak

Jeerapat¹

2022

ijcsrr

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“…Absence of poxin in ectromelia virus (commonly known as viral Schlafen due to its fusion with a Schlafen-like gene) results in a remarkable loss of virulence and a marked attenuation of infection, demonstrating the importance of this axis for protective immunity against poxviruses [28]. Poxin is highly conserved in orthopoxviruses (OPXV) but it is inactivated in MVA [29,30]. Whilst viruses carrying poxin effectively prevent STING activation, MVA infection of human and mouse cells results in strong induction of IFN and pro-inflammatory cytokines that is dependent on cGAS and STING [31][32][33] that is crucial for the establishment of cytotoxic T cell responses and memory T cell formation [34,35].…”

Section: Introductionmentioning

confidence: 99%

Disruption of the cGAS/STING axis does not impair sensing of MVA in BHK21 cells

Hood

Sumner

Motes

2022

Journal of General Virology

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Modified vaccinia Ankara (MVA) is an attenuated strain of vaccinia virus (VACV), a dsDNA virus that replicates its genome in the cytoplasm and as a result is canonically sensed by the cyclic GMP-AMP synthase (cGAS) and its downstream stimulator of interferon genes (STING). MVA has a highly restricted host range due to major deletions in its genome including inactivation of immunomodulatory genes, only being able to grow in avian cells and the hamster cell line BHK21. Here we studied the interplay between MVA and the cGAS/STING DNA in this permissive cell line and determined whether manipulation of this axis could impact MVA replication and cell responses. We demonstrate that BHK21 cells retain a functional cGAS/STING axis that responds to canonical DNA sensing agonists, upregulating interferon stimulated genes (ISGs). BHK21 cells also respond to MVA, but with a distinct ISG profile. This profile remains unaltered after CRISPR/Cas9 knock-out editing of STING and ablation of cytosolic DNA responses, indicating that MVA responses are independent of the cGAS/STING axis. Furthermore, infection by MVA diminishes the ability of BHK21 cells to respond to exogenous DNA suggesting that MVA still encodes uncharacterised inhibitors of DNA sensing. This suggests that using attenuated strains in permissive cell lines may assist in identification of novel host-virus interactions that may be of relevance to disease or the therapeutic applications of poxviruses.

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Structure of monkeypox virus poxin: implications for drug design

Duchoslav

Bouřa

2023

Arch Virol

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Monkeypox, or mpox, is a disease that has recently resurfaced and spread across the globe. Despite the availability of an FDA-approved vaccine (JYNNEOS) and an effective drug (tecovirimat), concerns remain over the possible recurrence of a viral pandemic. Like any other virus, mpox virus must overcome the immune system to replicate. Viruses have evolved various strategies to overcome both innate and adaptive immunity. Poxviruses possess an unusual nuclease, poxin, which cleaves 2'-3'-cGAMP, a cyclic dinucleotide, which is an important second messenger in the cGAS-STING signaling pathway. Here, we present the crystal structure of mpox poxin. The structure reveals a conserved, predominantly β-sheet fold and highlights the high conservation of the cGAMP binding site and of the catalytic residues His17, Tyr138, and Lys142. This research suggests that poxin inhibitors could be effective against multiple poxviruses.

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Poxvirus cGAMP nucleases: Clues and mysteries from a stolen gene

Cited by 15 publications

References 25 publications

Monkeypox: From Past to Present Outbreak

Monkeypox: From Past to Present Outbreak

Disruption of the cGAS/STING axis does not impair sensing of MVA in BHK21 cells

Structure of monkeypox virus poxin: implications for drug design

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