Disease relevance of Ectromelia

• Spina bifida and truncation of the tail and lumbosacral region (including abnormalities of the kidneys, urogenital tract, and hindgut) are the most conspicuous defects, leading in extreme cases to a sirenomelia ("mermaid tail") phenotype [1].
• Inhibition of type 1 cytokine-mediated inflammation by a soluble CD30 homologue encoded by ectromelia (mousepox) virus [2].
• Through the use of perforin-deficient mice, we were able to demonstrate a requirement for this molecule in the clearance of some viruses, such as ectromelia virus, whilst for others, such as vaccinia virus, perforin was less important but IFN-gamma was essential [3].
• Adoptive transfer of ectromelia virus meningitis was most efficient when donor-immune spleen cells and recipients were compatible in the K region of the H-2 gene complex [4].
• Here we show that vaccinia, ectromelia and cowpox viruses secrete from infected cells a soluble IL-18BP (vIL-18BP) that may modulate the host antiviral response [5].

High impact information on Ectromelia

• Retinoic acid has profound effects on vertebrate limb morphogenesis (refs 1-6, reviewed in refs 7-9), including in the mouse, where it can act as a teratogen generating phocomelia and bone defects [6].
• The finding of a CD30 homologue encoded by ectromelia virus suggests a role for CD30 in antiviral defense [2].
• We infected TNF receptor (TNFR)-deficient mice with the virulent murine pathogen, ectromelia virus (EV), and observed that otherwise resistant mice were susceptible to lethal infection [7].
• It was found that BALB/c-H-2db mice, which lack detectable cell-surface H-2L gene products, were able to generate influenza- and vaccinia-immune cytotoxic T cells which lyse D region-compatible target cells, although they have been reported to be incapable of making a similar response to ectromelia virus (7) [8].
• Phocomelia in infant whose mother took large doses of pyridoxine during pregnancy [9].

Chemical compound and disease context of Ectromelia

• Chromosomal studies on children with phocomelia, exposed to debendox during early pregnancy [10].
• The observation that the protein synthesized by ectromelia virus-infected cells reacted with only one of the three MAbs provided a means of mapping the gene encoding the glycoprotein [11].
• It was observed that expression of IL-4 by a thymidine kinase-positive ectromelia virus suppressed cytolytic responses of NK and CTL and the expression of gamma interferon by the latter [12].
• The patterns of anomalies of the two sisters do not fit into any of the syndromes featuring phocomelia; there was no prenatal exposure to thalidomide or any other possible teratogen [13].
• Exposure to 400 mg/kg hydroxyurea did not affect the progeny, whereas exposure to 500 or 600 mg/kg resulted in dose-dependent increases in fetal resorptions and malformations, including curly tails, abnormal limbs (oligodactyly, hemimelia, and amelia), and short ribs [14].

Biological context of Ectromelia

• Although a number of Grzs, including GrzM, have been shown to mediate target cell apoptosis in the presence of perforin, the biological activity of Grz has been restricted to control of a number of viral pathogens, including two natural mouse pathogens, ectromelia, and murine CMV (MCMV) [15].
• Haplotypes for a marker locus, D1Mit57, from the differential segment were determined in (D2.R4 x D2)F1 x D2 backcross mice, which were then infected with ectromelia virus [16].
• Using point mutagenesis, we analyzed the ectromelia virus IL-18BP to identify residues involved in binding [17].
• Maternal administration of a single dose of retinoic acid (vitamin A acid, 100 mg/kg) on either the 11th, 11 1/2, 12th, 12 1/2, 13th or 13 1/2 day of gestation produced phocomelia or partial phocomelia in ICR/DUB fetuses [18].
• We have reported two cases of sirenomelia sequence associated with a history of cocaine exposure during a major part or the entire extent of the first trimester of pregnancy [19].

Anatomical context of Ectromelia

• Our data suggest that inactivation of IL-18, and subsequent impairment of NK cell cytotoxicity, may be one mechanism by which ectromelia evades the host immune response [20].
• Expression of mouse interleukin-4 by a recombinant ectromelia virus suppresses cytolytic lymphocyte responses and overcomes genetic resistance to mousepox [12].
• Pathogenesis of caudal dysgenesis/sirenomelia induced by ochratoxin A in chick embryos [21].
• Hindlimb buds were maximally sensitive to 20 mg/kg of cyclophosphamide at 9 A.M. on day 11, and the predominant malformations formed were preaxial ectrodactyly and hemimelia [22].
• Although tibial hemimelia has been well documented in Dh mice, this study demonstrated a distinctive pattern of shortening of the tibia [23].

Gene context of Ectromelia

• Inactivating mutations in ESCO2 cause SC phocomelia and Roberts syndrome: no phenotype-genotype correlation [24].
• The ectromelia virus protein was found to block NF-kappaB activation and induction of IFN-gamma in response to IL-18 [5].
• The multidrug resistance gene mdr1a influences resistance to ectromelia virus infection by mechanisms other than conventional immunity [25].
• We employed mdr1a gene knock out (mdr1a-/-) mice and ectromelia virus (EV) to elucidate the role of P-gp in resistance to EV [25].
• Using mice deficient for granzyme A, we show here that granzyme A plays a crucial role in recovery from the natural mouse pathogen, ectromelia, by mechanisms other than cytolytic activity [26].

Analytical, diagnostic and therapeutic context of Ectromelia

• To determine whether this LP-BM5 MuLV infection would affect the innate resistance of B6 mice to a naturally occurring, highly virulent murine pathogen, mice were exposed to ectromelia virus at various times after treatment with LP-BM5 viruses [27].
• The lesions imaged were fibular hemimelia (n = 5), tibial hemimelia (n = 5), and congenital constriction bands (n = 3) [28].

References