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Poxvirus genomes encode a secreted, soluble protein that preferentially inhibits beta chemokine activity yet lacks sequence homology to known chemokine receptors.

Publication ,  Journal Article
Smith, CA; Smith, TD; Smolak, PJ; Friend, D; Hagen, H; Gerhart, M; Park, L; Pickup, DJ; Torrance, D; Mohler, K; Schooley, K; Goodwin, RG
Published in: Virology
September 29, 1997

Poxvirus genomes encode several proteins which inhibit specific elements of the host immune response. We show the "35K" virulence gene in variola and cowpox viruses, whose vaccinia and Shope fibroma virus equivalents are strongly conserved in sequence, actually encodes a secreted soluble protein with high-affinity binding to virtually all known beta chemokines, but only weak or no affinity to the alpha and gamma classes. The viral protein completely inhibits the biological activity of monocyte chemotactic protein-1 (MCP-1) by competitive inhibition of chemokine binding to cellular receptors. As all beta chemokines are also shown to cross-compete with MCP1 binding to the viral protein, we conclude that this viral chemokine inhibitor (vCCI) not only interacts through a common binding site, but is likely a potent general inhibitor of beta chemokine activity. Unlike many poxvirus virulence genes to date, which are clearly altered forms of acquired cellular genes of the vertebrate immune system, this viral chemokine inhibitor (vCCI) shares no sequence homology with known proteins, including known cellular chemokine receptors, all of which are multiple membrane-spanning proteins. Thus, vCCI presumably has no cellular analogue and instead may be the product of unrelenting sequence variations which gave rise to a completely new protein with similar binding properties to native chemokine receptors. The proposed function of vCCI is inhibition of the proinflammatory (antiviral) activities of beta chemokines.

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Published In

Virology

DOI

ISSN

0042-6822

Publication Date

September 29, 1997

Volume

236

Issue

2

Start / End Page

316 / 327

Location

United States

Related Subject Headings

  • Virulence
  • Virology
  • Viral Proteins
  • Variola virus
  • Solubility
  • Sequence Homology, Amino Acid
  • Receptors, Chemokine
  • Poxviridae
  • Polymerase Chain Reaction
  • Molecular Sequence Data
 

Citation

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Smith, C. A., Smith, T. D., Smolak, P. J., Friend, D., Hagen, H., Gerhart, M., … Goodwin, R. G. (1997). Poxvirus genomes encode a secreted, soluble protein that preferentially inhibits beta chemokine activity yet lacks sequence homology to known chemokine receptors. Virology, 236(2), 316–327. https://doi.org/10.1006/viro.1997.8730
Smith, C. A., T. D. Smith, P. J. Smolak, D. Friend, H. Hagen, M. Gerhart, L. Park, et al. “Poxvirus genomes encode a secreted, soluble protein that preferentially inhibits beta chemokine activity yet lacks sequence homology to known chemokine receptors.Virology 236, no. 2 (September 29, 1997): 316–27. https://doi.org/10.1006/viro.1997.8730.
Smith, C. A., et al. “Poxvirus genomes encode a secreted, soluble protein that preferentially inhibits beta chemokine activity yet lacks sequence homology to known chemokine receptors.Virology, vol. 236, no. 2, Sept. 1997, pp. 316–27. Pubmed, doi:10.1006/viro.1997.8730.
Smith CA, Smith TD, Smolak PJ, Friend D, Hagen H, Gerhart M, Park L, Pickup DJ, Torrance D, Mohler K, Schooley K, Goodwin RG. Poxvirus genomes encode a secreted, soluble protein that preferentially inhibits beta chemokine activity yet lacks sequence homology to known chemokine receptors. Virology. 1997 Sep 29;236(2):316–327.
Journal cover image

Published In

Virology

DOI

ISSN

0042-6822

Publication Date

September 29, 1997

Volume

236

Issue

2

Start / End Page

316 / 327

Location

United States

Related Subject Headings

  • Virulence
  • Virology
  • Viral Proteins
  • Variola virus
  • Solubility
  • Sequence Homology, Amino Acid
  • Receptors, Chemokine
  • Poxviridae
  • Polymerase Chain Reaction
  • Molecular Sequence Data