Cowpox virus encodes a fifth member of the tumor necrosis factor receptor family: A soluble, secreted CD30 homologue

Panus, Joanne Fanelli; Smith, Craig A.; Ray, Caroline A.; Smith, Terri; Patel, Dhavalkumar D.; Pickup, David J.

doi:10.1073/pnas.122238599

Cited by 62 publications

(39 citation statements)

References 80 publications

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“…HSPV009 encodes a truncated orthologue of CPXV GRI-90 D12L product, a protein similar to the CrmB carboxyl terminus and whose orthologue in ECTV was recently characterized as a secreted chemokine binding protein (7). HSPV010 encodes an intact orthologue of CD30 TNFRlike proteins present in CPXV and ECTV, proteins able to bind CD30 ligands and/or have immunomodulatory effects (63,72). HSPV left-end sequences also contain genes for three ankyrin repeat proteins absent in VACV.…”

Section: Resultsmentioning

confidence: 99%

Genome of Horsepox Virus

Tulman

Delhon

Afonso

et al. 2006

J Virol

125

117

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The genus Orthopoxvirus includes members of the family Poxviridae historically relevant to human health-variola virus (VARV), the etiologic agent of smallpox, and vaccinia virus (VACV), the vaccine virus used to eradicate smallpox (32). Other orthopoxviruses (OPVs), similar to VACV, are zoonotic and significant for human health, including monkeypox virus (MPXV) and cowpox virus (CPXV) (33). Still others, similar to VARV, remain restricted to specific, albeit nonhuman, hosts, including camelpox virus (CMLV) in camels and ectromelia virus (ECTV) in mice. Recent developments have heightened interest in OPV virulence and host range, including the threats of deliberate VARV reintroduction, virulence associated with preemptive smallpox vaccination and use of VACV-based recombinant vaccines, and the introduction of MPXV into the United States (16,28,69,83). Isolation of OPV from infected animals and humans during limited disease outbreaks or from animals in the wild suggests that additional OPVs circulating in nature could represent an emerging disease threat (24,25,27,32,46,49,50,90).Given their importance, OPVs have been extensively studied as models of poxviral molecular biology, genomics, genetics, and virus-host interaction (19,33,59). Research has revealed that OPVs contain approximately 170 to 230 genes, with those in central genomic regions generally involved in poxviral intracytoplasmic replication and those in terminal genomic regions involved or potentially involved in virus-host interactions, including manipulation of host immune or cellular apoptotic responses (4,19,59,60,82,87).Comparative analysis of completely sequenced OPV genomes, including most known OPV species and several strains of VARV, VACV and the closely related rabbitpox virus (RPXV), MPXV, CMLV, and CPXV has begun to reveal the degree of variability within the genus Orthopoxvirus, verifying that terminal genomic regions are the most variable and thus likely to contribute to the virulence and host range characteristics of different OPVs (2,9,21,22,36,39,51,52,54,58,78,80,81). The precise roles and contributions of many variable genes and gene complements in OPV virulence and host range, however, remain to be fully characterized. It is likely that complete genomic data from uncharacterized OPV isolates will aid in OPV gene identification and functional characterization, while also providing information regarding the pathogenic potential of the virus.

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Section: Resultsmentioning

confidence: 99%

Genome of Horsepox Virus

Tulman

Delhon

Afonso

et al. 2006

J Virol

125

117

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“…Four additional poxvirus TNFR homologues, the cytokine response modifying (Crm) proteins, which display different ligand specificities, have been identified, with CrmB and CrmD binding both TNF and lymphotoxin ␣, whereas CrmC and CrmE bind only TNF (103)(104)(105)(106). The poxviruses, cowpox and ectromelia (mousepox), also encode a soluble, secreted homologue of CD30, which can bind CD30L with high affinity, preventing its receptor binding and thereby inhibiting Th2-mediated inflammation in vivo (107,108). Soluble viral homologues of the type 1 IFN receptor (109,110), the IFN-␥ receptor (111), IL-1RII (112,113), and IL-18 binding protein (94) have also been identified.…”

Section: Virally Encoded Soluble Cytokine Receptorsmentioning

confidence: 99%

Mechanisms of Soluble Cytokine Receptor Generation

Levine

2004

The Journal of Immunology

149

124

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Soluble cytokine receptors regulate inflammatory and immune events by functioning as agonists or antagonists of cytokine signaling. As such, they act within complex receptor systems that include signaling receptors, nonsignaling decoy receptors, receptor-associated proteins, and soluble receptor antagonists. Soluble cytokine receptors can be generated by several mechanisms, which include proteolytic cleavage of receptor ectodomains, alternative splicing of mRNA transcripts, transcription of distinct genes that encode soluble cytokine-binding proteins, release of full-length receptors within the context of exosome-like vesicles, and cleavage of GPI-anchored receptors. Furthermore, the important role of soluble cytokine receptors in regulating host defense mechanisms is evidenced by viruses that encode soluble homologues of mammalian receptors and thereby evade innate host immune responses via the sequestration of essential cytokines.

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“…Some TNFR reading frames such crmC encoded by the vvUSSR A53R open reading frame are functional, whereas crmC is not functional in vvCopenhagen [Reading et al, 2002]. The finding of soluble CD30R solely from ectromelia virus suggests unique host selective pressures [Panus et al, 2002]. Differences in sTNFR expression among Orthopoxviruses have been attributed to episodic TNF-driven evolutionary selection [Johnston and McFadden, 2003].…”

Section: The Poxviruses Express Proteins That Downmodulate the Host Imentioning

confidence: 99%

Viral appropriation of apoptotic and NF‐κB signaling pathways

Bowie

Zhan

Marshall

2004

J of Cellular Biochemistry

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Viruses utilize a variety of strategies to evade the host immune response and replicate in the cells they infect. The comparatively large genomes of the Orthopoxviruses and gammaherpesviruses encode several immunomodulatory proteins that are homologous to component of the innate immune system of host cells, which are reviewed here. However, the viral mechanisms used to survive host responses are quite distinct between these two virus families. Poxviruses undergo continuous lytic replication in the host cytoplasm while expressing many genes that inhibit innate immune responses. In contrast, herpesviruses persist in a latent state during much of their lifecycle while expressing only a limited number of relatively non-immunogenic viral proteins, thereby avoiding the adaptive immune response. Poxviruses suppress, whereas latent gammaherpesviruses activate, signaling by NF-kappaB, yet both viruses target similar host signaling pathways to suppress the apoptotic response. Here, modulation of apoptotic and NF-kappaB signal transduction pathways are examined as examples of common pathways appropriated in contrasting ways by herpesviruses and poxviruses.

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Cowpox virus encodes a fifth member of the tumor necrosis factor receptor family: A soluble, secreted CD30 homologue

Cited by 62 publications

References 80 publications

Genome of Horsepox Virus

Genome of Horsepox Virus

Mechanisms of Soluble Cytokine Receptor Generation

Viral appropriation of apoptotic and NF‐κB signaling pathways

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