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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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 Date

  • September 1997

Published In

Volume / Issue

  • 236 / 2

Start / End Page

  • 316 - 327

PubMed ID

  • 9325239

Pubmed Central ID

  • 9325239

Electronic International Standard Serial Number (EISSN)

  • 2514-4138

International Standard Serial Number (ISSN)

  • 1096-0341

Digital Object Identifier (DOI)

  • 10.1006/viro.1997.8730

Language

  • eng