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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Cowpox


High impact information on Cowpox

  • The activity of ICE can be specifically inhibited by the product of crmA, a cytokine response modifier gene encoded by cowpox virus [6].
  • In contrast, the cowpox virus protease inhibitor CrmA blocked Fas/APO-1-transduced apoptosis, but did not affect cell death induced by gamma-radiation or serum deprivation [7].
  • Sequence analysis of a region of the genome that is type-specific for cowpox virus identified a gene, vCD30, encoding a soluble, secreted protein that is the fifth member of the tumor necrosis factor receptor family known to be encoded by cowpox virus [8].
  • Cowpox virus encodes a fifth member of the tumor necrosis factor receptor family: a soluble, secreted CD30 homologue [8].
  • Structure of a soluble secreted chemokine inhibitor vCCI (p35) from cowpox virus [9].

Chemical compound and disease context of Cowpox

  • The cleavage at the IETD downward arrowS site required a protease activity that was selectively inhibited by the peptide, Ac-IETD-CHO (acetyl-IETD-aldehyde), and other protease inhibitors, such as the cowpox viral serine protease inhibitor, CrmA, and N-alpha-tosyl-L-phenylalanine chloromethyl ketone [10].
  • In contrast to CDV, HDP-CDV is orally bioavailable and has been reported to be orally active in lethal cowpox virus infection in mice [11].
  • General inhibitor of caspases, cow pox virus-derived CrmA, also inhibited TNF-induced mitochondrial changes indicating that early caspase activation occurs upstream from mitochondrial changes [12].
  • A new series of ether lipid esters of cidofovir (CDV) were evaluated against vaccinia and cowpox viruses [13].
  • Using a combinatorial method, variants of the basic isatin-beta-thiosemicarbazone structure were prepared and examined for cytotoxicity and antiviral activity in vaccinia virus- and cowpox virus-infected human cells [14].

Biological context of Cowpox


Anatomical context of Cowpox

  • In addition, overexpression of the cowpox virus protein CrmA, a molecule with inhibitory potential on caspase-1 and caspase-8, specifically involved in Fas-induced signaling, protected T cells from being destroyed by the neoplastic cells or the agonistic anti-Fas MoAb [20].
  • DNA of ph3D was related to the A25L gene, which corresponds to the A-type inclusion body gene of cowpox virus [21].
  • Plasma membrane localization and fusion inhibitory activity of the cowpox virus serpin SPI-3 require a functional signal sequence and the virus encoded hemagglutinin [22].
  • The chemoattractant activity induced in ovo by white cowpox virus infection has sedimentation characteristics in sucrose density gradients that are similar to leukotactic factors shown previously to be present in the allantoic fluid of chick embryos infected with paramyxoviruses [23].

Gene context of Cowpox

  • The Fas-apoptotic pathway is potently inhibited by the cowpox serpin CrmA, suggesting that Mch5 could be the target of this serpin [24].
  • In addition, the reactive center loop of PI9 exhibits 54% identity with residues found in the reactive center loop of the cowpox virus CrmA serpin [25].
  • Here we show that vaccinia virus and other orthopoxviruses (cowpox and camelpox) express a secreted 35-kDa chemokine binding protein (vCKBP) with no sequence similarity to known cellular chemokine receptors [26].
  • This degradation could be inhibited by the broad-spectrum caspase inhibitor zVAD-fmk or by expression of the cowpox virus-derived inhibitor CrmA, suggesting that TXBP151 is a novel substrate for caspase family members [27].
  • Activation of the CD95-specific set of kinases was prevented by treating cells with the ICE-inhibiting peptide N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD-fmk) or by overexpression of the cow pox virus serpin CrmA [28].

Analytical, diagnostic and therapeutic context of Cowpox


  1. A third distinct tumor necrosis factor receptor of orthopoxviruses. Loparev, V.N., Parsons, J.M., Knight, J.C., Panus, J.F., Ray, C.A., Buller, R.M., Pickup, D.J., Esposito, J.J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  2. Hemorrhage in lesions caused by cowpox virus is induced by a viral protein that is related to plasma protein inhibitors of serine proteases. Pickup, D.J., Ink, B.S., Hu, W., Ray, C.A., Joklik, W.K. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  3. Structural and functional studies of a 39,000-Mr immunodominant protein of vaccinia virus. Maa, J.S., Esteban, M. J. Virol. (1987) [Pubmed]
  4. Cell-mediated cytotoxicity in recovery from poxvirus infections. Müllbacher, A. Rev. Med. Virol. (2003) [Pubmed]
  5. Structure and cell surface maturation of the attachment glycoprotein of human respiratory syncytial virus in a cell line deficient in O glycosylation. Wertz, G.W., Krieger, M., Ball, L.A. J. Virol. (1989) [Pubmed]
  6. Prevention of vertebrate neuronal death by the crmA gene. Gagliardini, V., Fernandez, P.A., Lee, R.K., Drexler, H.C., Rotello, R.J., Fishman, M.C., Yuan, J. Science (1994) [Pubmed]
  7. Bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis. Strasser, A., Harris, A.W., Huang, D.C., Krammer, P.H., Cory, S. EMBO J. (1995) [Pubmed]
  8. Cowpox virus encodes a fifth member of the tumor necrosis factor receptor family: a soluble, secreted CD30 homologue. Panus, J.F., Smith, C.A., Ray, C.A., Smith, T.D., Patel, D.D., Pickup, D.J. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  9. Structure of a soluble secreted chemokine inhibitor vCCI (p35) from cowpox virus. Carfí, A., Smith, C.A., Smolak, P.J., McGrew, J., Wiley, D.C. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  10. A sequential two-step mechanism for the production of the mature p17:p12 form of caspase-3 in vitro. Han, Z., Hendrickson, E.A., Bremner, T.A., Wyche, J.H. J. Biol. Chem. (1997) [Pubmed]
  11. Increased antiviral activity of 1-O-hexadecyloxypropyl-[2-(14)C]cidofovir in MRC-5 human lung fibroblasts is explained by unique cellular uptake and metabolism. Aldern, K.A., Ciesla, S.L., Winegarden, K.L., Hostetler, K.Y. Mol. Pharmacol. (2003) [Pubmed]
  12. TNF-induced mitochondrial changes and activation of apoptotic proteases are inhibited by A20. Wissing, D., Mouritzen, H., Jäättelä, M. Free Radic. Biol. Med. (1998) [Pubmed]
  13. Inhibitory activity of alkoxyalkyl and alkyl esters of cidofovir and cyclic cidofovir against orthopoxvirus replication in vitro. Keith, K.A., Wan, W.B., Ciesla, S.L., Beadle, J.R., Hostetler, K.Y., Kern, E.R. Antimicrob. Agents Chemother. (2004) [Pubmed]
  14. Combinatorial optimization of isatin-beta-thiosemicarbazones as anti-poxvirus agents. Pirrung, M.C., Pansare, S.V., Sarma, K.D., Keith, K.A., Kern, E.R. J. Med. Chem. (2005) [Pubmed]
  15. Orthopoxvirus fusion inhibitor glycoprotein SPI-3 (open reading frame K2L) contains motifs characteristic of serine proteinase inhibitors that are not required for control of cell fusion. Turner, P.C., Moyer, R.W. J. Virol. (1995) [Pubmed]
  16. Vaccinia, cowpox, and camelpox viruses encode soluble gamma interferon receptors with novel broad species specificity. Alcamí, A., Smith, G.L. J. Virol. (1995) [Pubmed]
  17. The cowpox virus SPI-3 and myxoma virus SERP1 serpins are not functionally interchangeable despite their similar proteinase inhibition profiles in vitro. Wang, Y.X., Turner, P.C., Ness, T.L., Moon, K.B., Schoeb, T.R., Moyer, R.W. Virology (2000) [Pubmed]
  18. The Amsacta moorei entomopoxvirus spheroidin gene is improperly transcribed in vertebrate poxviruses. Hall, R.L., Li, Y., Feller, J., Moyer, R.W. Virology (1996) [Pubmed]
  19. Two early vaccinia virus genes encode polypeptides related to protein kinases. Howard, S.T., Smith, G.L. J. Gen. Virol. (1989) [Pubmed]
  20. Constitutive expression of Fas (Apo-1/CD95) ligand on multiple myeloma cells: a potential mechanism of tumor-induced suppression of immune surveillance. Villunger, A., Egle, A., Marschitz, I., Kos, M., Böck, G., Ludwig, H., Geley, S., Kofler, R., Greil, R. Blood (1997) [Pubmed]
  21. Epitope detection in the envelope of intracellular naked orthopox viruses and identification of encoding genes. Czerny, C.P., Johann, S., Hölzle, L., Meyer, H. Virology (1994) [Pubmed]
  22. Plasma membrane localization and fusion inhibitory activity of the cowpox virus serpin SPI-3 require a functional signal sequence and the virus encoded hemagglutinin. Brum, L.M., Turner, P.C., Devick, H., Baquero, M.T., Moyer, R.W. Virology (2003) [Pubmed]
  23. Inflammatory responses and the generation of chemoattractant activity in cowpox virus-infected tissues. Chua, T.P., Smith, C.E., Reith, R.W., Williamson, J.D. Immunology (1990) [Pubmed]
  24. Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases. Srinivasula, S.M., Ahmad, M., Fernandes-Alnemri, T., Litwack, G., Alnemri, E.S. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  25. Molecular cloning, expression, and partial characterization of two novel members of the ovalbumin family of serine proteinase inhibitors. Sprecher, C.A., Morgenstern, K.A., Mathewes, S., Dahlen, J.R., Schrader, S.K., Foster, D.C., Kisiel, W. J. Biol. Chem. (1995) [Pubmed]
  26. Blockade of chemokine activity by a soluble chemokine binding protein from vaccinia virus. Alcamí, A., Symons, J.A., Collins, P.D., Williams, T.J., Smith, G.L. J. Immunol. (1998) [Pubmed]
  27. The zinc finger protein A20 interacts with a novel anti-apoptotic protein which is cleaved by specific caspases. De Valck, D., Jin, D.Y., Heyninck, K., Van de Craen, M., Contreras, R., Fiers, W., Jeang, K.T., Beyaert, R. Oncogene (1999) [Pubmed]
  28. CD95 (APO-1/Fas) induces activation of SAP kinases downstream of ICE-like proteases. Cahill, M.A., Peter, M.E., Kischkel, F.C., Chinnaiyan, A.M., Dixit, V.M., Krammer, P.H., Nordheim, A. Oncogene (1996) [Pubmed]
  29. Cidofovir protects mice against lethal aerosol or intranasal cowpox virus challenge. Bray, M., Martinez, M., Smee, D.F., Kefauver, D., Thompson, E., Huggins, J.W. J. Infect. Dis. (2000) [Pubmed]
  30. The genome of cowpox virus contains a gene related to those encoding the epidermal growth factor, transforming growth factor alpha and vaccinia growth factor. da Fonseca, F.G., Silva, R.L., Marques, J.T., Ferreira, P.C., Kroon, E.G. Virus Genes (1999) [Pubmed]
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