A novel cypovirus found in a betabaculovirus co-infection context contains a poxvirus immune nuclease (poxin)-related gene

Silva, Leonardo A. da; Ardisson-Araújo, Daniel Mendes Pereira; Camargo, Brenda Rabelo de; Souza, Marlinda Lobo de; Ribeiro, Bergmann Morais

doi:10.1099/jgv.0.001413

Cited by 4 publications

(3 citation statements)

References 44 publications

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“…Lepidopteran poxin enzymes cluster within Group 3, and have been shown to be highly upregulated after infection with various pathogens, including alphabaculoviruses and bacteria, providing evidence for a role in immunity or immune regulation (Shrestha et al, 2019;Woon Shin et al, 1998). Group 4 is formed by poxin proteins from the genomes of several additional lepidopteran viruses: betabaculoviruses (also called granuloviruses), cypoviruses (doublestranded RNA viruses in the family Reoviridae), and betaentomopoxviruses ( Figure 1B) (Silva et al, 2020). The vast evolutionary distance between these DNA and RNA viral families suggests related poxin genes may have been transferred between viruses within coinfected cells (Silva et al, 2020;Thézé et al, 2015).…”

Section: Poxins Are a Diverse Family Of 2′3′-cgamp Nucleasesmentioning

confidence: 99%

“…Group 4 is formed by poxin proteins from the genomes of several additional lepidopteran viruses: betabaculoviruses (also called granuloviruses), cypoviruses (doublestranded RNA viruses in the family Reoviridae), and betaentomopoxviruses ( Figure 1B) (Silva et al, 2020). The vast evolutionary distance between these DNA and RNA viral families suggests related poxin genes may have been transferred between viruses within coinfected cells (Silva et al, 2020;Thézé et al, 2015). Notably, the enormous diversity of poxin enzymes in insect pathogens and moth and butterfly genomes confirms a broad role for 2′3′-cGAMP degradation, and strongly suggests these genomes served as a source for emergence of poxins in mammalian poxviruses.…”

Section: Poxins Are a Diverse Family Of 2′3′-cgamp Nucleasesmentioning

confidence: 99%

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Structures of diverse poxin cGAMP nucleases reveal a widespread role for cGAS-STING evasion in host–pathogen conflict

Eaglesham

McCarty

Kranzusch

2020

eLife

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DNA viruses in the family Poxviridae encode poxin enzymes that degrade the immune second messenger 2′3′-cGAMP to inhibit cGAS-STING immunity in mammalian cells. The closest homologs of poxin exist in the genomes of insect viruses suggesting a key mechanism of cGAS-STING evasion may have evolved outside of mammalian biology. Here we use a biochemical and structural approach to discover a broad family of 369 poxins encoded in diverse viral and animal genomes and define a prominent role for 2′3′-cGAMP cleavage in metazoan host-pathogen conflict. Structures of insect poxins reveal unexpected homology to flavivirus proteases and enable identification of functional self-cleaving poxins in RNA-virus polyproteins. Our data suggest widespread 2′3′-cGAMP signaling in insect antiviral immunity and explain how a family of cGAS-STING evasion enzymes evolved from viral proteases through gain of secondary nuclease activity. Poxin acquisition by poxviruses demonstrates the importance of environmental connections in shaping evolution of mammalian pathogens.

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Section: Poxins Are a Diverse Family Of 2′3′-cgamp Nucleasesmentioning

confidence: 99%

Section: Poxins Are a Diverse Family Of 2′3′-cgamp Nucleasesmentioning

confidence: 99%

Structures of diverse poxin cGAMP nucleases reveal a widespread role for cGAS-STING evasion in host–pathogen conflict

Eaglesham

McCarty

Kranzusch

2020

eLife

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“…Since then, increasing evidence for the central role played by these cGAMP-specific nucleases in pathogen evasion has been published. In addition to poxviruses, different classes of pathogens have been described to encode proteins with similar functions, including baculovirus [ 13 ], cypovirus [ 14 ], ribovirus [ 15 ], and parasitoid wasps [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Improving poxvirus-mediated antitumor immune responses by deleting viral cGAMP-specific nuclease

Riederer¹,

Canizo

Navas

et al. 2023

Cancer Gene Ther

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AbstractcGAMP-specific nucleases (poxins) are a recently described family of proteins dedicated to obstructing cyclic GMP-AMP synthase signaling (cGAS), an important sensor triggered by cytoplasmic viral replication that activates type I interferon (IFN) production. The B2R gene of vaccinia viruses (VACV) codes for one of these nucleases. Here, we evaluated the effects of inactivating the VACV B2 nuclease in the context of an oncolytic VACV. VACV are widely used as anti-cancer vectors due to their capacity to activate immune responses directed against tumor antigens. We aimed to elicit robust antitumor immunity by preventing viral inactivation of the cGAS/STING/IRF3 pathway after infection of cancer cells. Activation of such a pathway is associated with a dominant T helper 1 (Th1) cell differentiation of the response, which benefits antitumor outcomes. Deletion of the B2R gene resulted in enhanced IRF3 phosphorylation and type I IFN expression after infection of tumor cells, while effective VACV replication remained unimpaired, both in vitro and in vivo. In syngeneic mouse tumor models, the absence of the VACV cGAMP-specific nuclease translated into improved antitumor activity, which was associated with antitumor immunity directed against tumor epitopes.

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Ecological safety of insecticide based on entomopathogenic virus DsCPV-1 for nontarget invertebrates

Belevitch,

Yurchenko,

Kharlamova

et al. 2024

Sci Rep

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For the first time under laboratory conditions, the virulence of a unique cypovirus strain, DsCPV-1, which has broad host specificity, was tested on nontarget aquatic organisms (natural species: Gammarus lacustris , Anopheles messeae , Coenagrion lunulatum , Cloeon robusta , Chironomus sp., Ilyocoris cimicoides , and Plea minutissima ; laboratory species: Aedes aegypti and Daphnia magna ), a terrestrial pollinator species ( Apis mellifera ), and an entomophage ( Podisus maculiventris ). The probability of this virus’s accumulation in the bodies of invertebrates and of its transmission along a trophic chain was evaluated by two approaches: bioassays and a molecular diagnostic analysis. In the bioassays, there was no significant increase in mortality among all the tested aquatic and terrestrial nontarget species exposed to DsCPV-1 as compared with control groups (no virus). When we fed Podisus maculiventris with caterpillars having active DsCPV-1 infection (i.e., with the virus replicating in the host) no viral replication was observed in bug. No replication was also observed in mosquitos as well as in bee after viral treatment. Thus, the results show that the DsCPV-1 virus has excellent environmental safety toward many invertebrate species and can be recommended for the control of lepidopteran pests in forestry and agriculture as insecticide with light effect on environment. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-78471-7.

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A novel cypovirus found in a betabaculovirus co-infection context contains a poxvirus immune nuclease (poxin)-related gene

Cited by 4 publications

References 44 publications

Structures of diverse poxin cGAMP nucleases reveal a widespread role for cGAS-STING evasion in host–pathogen conflict

Structures of diverse poxin cGAMP nucleases reveal a widespread role for cGAS-STING evasion in host–pathogen conflict

Improving poxvirus-mediated antitumor immune responses by deleting viral cGAMP-specific nuclease

Ecological safety of insecticide based on entomopathogenic virus DsCPV-1 for nontarget invertebrates

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