ArticleJournal of immunology (Baltimore, Md. : 1950)2009
Smallpox inhibitor of complement enzymes (SPICE): dissecting functional sites and abrogating activity.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Monkeypox virus clade IIb isolate exhibits reduced virulence relative to clade IIa isolates in multiple murine models.Journal of virology · 2026Article
- SARS-CoV-2 nucleocapsid protein forms complexes with soluble complement regulatory proteins that can bind to the virion.Scientific reports · 2026Article
- Review
- Role of Electrostatic Hotspots in the Selectivity of Complement Control Proteins Toward Human and Bovine Complement Inhibition.Frontiers in molecular biosciences · 2021Article
- Spatially conserved motifs in complement control protein domains determine functionality in regulators of complement activation-family proteins.Communications biology · 2019Article
- Article
- Review
- Species Specificity of Vaccinia Virus Complement Control Protein for the Bovine Classical Pathway Is Governed Primarily by Direct Interaction of Its Acidic Residues with Factor I.Journal of virology · 2017Article
- Regulators of complement activity mediate inhibitory mechanisms through a common C3b-binding mode.The EMBO journal · 2016Article
- Complement regulator CD46: genetic variants and disease associations.Human genomics · 2015Review
- Glycosylated and nonglycosylated complement control protein of the lister strain of vaccinia virus.Clinical and vaccine immunology : CVI · 2014Article
- Inhibitors of C5 complement enhance vaccinia virus oncolysis.Cancer gene therapy · 2013Article
- Dissection of functional sites in herpesvirus saimiri complement control protein homolog.Journal of virology · 2013Article
- Autoantibody stabilization of the classical pathway C3 convertase leading to C3 deficiency and Neisserial sepsis: C4 nephritic factor revisited.Clinical immunology (Orlando, Fla.) · 2012Review
- Enzyme-linked immunosorbent assay (ELISA) and blocking with bovine serum albumin (BSA)--not all BSAs are alike.Journal of immunological methods · 2012Article
- Article
- Disabling complement regulatory activities of vaccinia virus complement control protein reduces vaccinia virus pathogenicity.Vaccine · 2011Article
- The vaccinia virus A56 protein: a multifunctional transmembrane glycoprotein that anchors two secreted viral proteins.The Journal of general virology · 2011Review
- The Vaccinia virus complement control protein modulates adaptive immune responses during infection.Journal of virology · 2011Article
- Generation and characterization of a large panel of murine monoclonal antibodies against vaccinia virus.Virology · 2011Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Although smallpox was eradicated as a global illness more than 30 years ago, variola virus and other related pathogenic poxviruses, such as monkeypox, remain potential bioterrorist weapons or could re-emerge as natural infections. Poxviruses express virulence factors that down-modulate the host's immune system. We previously compared functional profiles of the poxviral complement inhibitors of smallpox, vaccinia, and monkeypox known as SPICE, VCP (or VICE), and MOPICE, respectively. SPICE was the most potent regulator of human complement and attached to cells via glycosaminoglycans. The major goals of the present study were to further characterize the complement regulatory and heparin binding sites of SPICE and to evaluate a mAb that abrogates its function. Using substitution mutagenesis, we established that (1) elimination of the three heparin binding sites severely decreases but does not eliminate glycosaminoglycan binding, (2) there is a hierarchy of activity for heparin binding among the three sites, and (3) complement regulatory sites overlap with each of the three heparin binding motifs. By creating chimeras with interchanges of SPICE and VCP residues, a combination of two SPICE amino acids (H77 plus K120) enhances VCP activity approximately 200-fold. Also, SPICE residue L131 is critical for both complement regulatory function and accounts for the electrophoretic differences between SPICE and VCP. An evolutionary history for these structure-function adaptations of SPICE is proposed. Finally, we identified and characterized a mAb that inhibits the complement regulatory activity of SPICE, MOPICE, and VCP and thus could be used as a therapeutic agent.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.