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

被引：162

作者：

Smith, CA ^{[1
]}

Smith, TD ^{[1
]}

Smolak, PJ ^{[1
]}

Friend, D ^{[1
]}

Hagen, H ^{[1
]}

Gerhart, M ^{[1
]}

Park, L ^{[1
]}

Pickup, DJ ^{[1
]}

Torrance, D ^{[1
]}

Mohler, K ^{[1
]}

Schooley, K ^{[1
]}

Goodwin, RG ^{[1
]}

机构：

[1] DUKE UNIV,MED CTR,DEPT MICROBIOL,DURHAM,NC 27710

来源：

VIROLOGY | 1997年 / 236卷 / 02期

关键词：

D O I：

10.1006/viro.1997.8730

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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 MCPI 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. (C) 1997 Academic Press.

引用

页码：316 / 327

页数：12

共 43 条

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