Poxviruses chemokine receptors

Luttichau HR, Stine J, Boesen TP, et al. A highly selective CC chemokine receptor (CCR)8 antagonist encoded by the poxvirus molluscum contagiosum. J Exp Med 2000 191 171-80. 

Virally encoded chemokines have also been discovered, in several herpesviruses (e.g. HHV-8, mouse cytomegalovirus) and in molluscum conta-giosum virus (MCV), a human poxvirus which causes the skin disease molluscum contagiosum. Interestingly, broad-spectrum chemokine receptor antagonist activity has been reported for several of these molecules, including vMIP-II of HHV-8 and MC148R of... 

Molecular Mimicry of Chemokines and Chemokine Receptors by Poxviruses... 

The K2R ORF of SPV, a poxvirus that causes mild infections in pigs, encodes a 370 amino acid protein with -30% amino acid sequence identity to mammalian chemokine receptors. A truncated and probably non-functional copy of the K2R ORF, designated C3L, is found at the other end of the viral genome. 

The use of viral chemokine/receptor mimics and inhibitors identified in particular virus families such as herpesviruses, poxviruses and HIV indicates their importance in pathogensis of these viruses, either for evasion of the immune response as with poxviruses and herpesviruses or addtionally the use of recptors for viral entry as with HIV and poxviruses. Further studies will almost certainly identify a greater range of viruses producing such mimics. 

Smith CA, Smith TD, Smolak PJ et al. Poxvirus genomes encode a secreted, soluble protein that preferentially inhibits beta chemokine activity yet lacks sequence homology to known chemokine receptors. Virology 1997 236(2) 316-327. 

Figure 16.1 Mechanisms of chemokine inhibition by the CKBPs encoded by pathogens. Chemokines interact with CACs present at the surface ofendothelial cells and are presented to the leukocytes. The chemokine receptors expressed at the surface of leukocytes interact with chemokines and intracellular signaling is triggered to induce cell migration. The CKBPs may have broad chemokine binding specificity, such as the poxvirus 35-kDa protein, the gammaherpesvirus M3 protein orthe MYXVM-...

The Smallpox Virus-Encoded Chemokine Receptor (SECRET) Domain from Poxviruses... 

The copied host-defense genes are primarily found in two classes of large DNA viruses, the poxviruses and the herpesviruses, where examples of copied cytokines, cytokine receptors, chemokines and chemokine receptors, complement-control proteins, and other cytokine-regulatory proteins (3,6,9,10) are known the sequence relationship of the viral and host homolog in these examples tends to be rather weak (25 5% amino... 

Several secreted virally encoded proteins may modulate the chemokine system by binding to chemokines. These proteins have been designated as chemokine-binding proteins (CBPs), and to date, CBPs have been described only in poxviruses (Table 1). These proteins are not receptor mimics and may mediate their actions through novel mechanisms. Two classes of CBPs have been described and have been referred to as type I and type-II. Members of these two families can bind a variety of chemokines, however, interestingly, they share no homology with each other, chemokines/chemokine receptors or any other known proteins. It should be noted that not all poxviruses encode CBPs ... 

Smith, C. A., Smith, T. D., Smolak, P. J., Friend, D., Hagen, H., Gerhart, M., Park, L., Pickup, D. J., Torrance, D., Mohler, K., Schooley, K., and 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 236,316-327. 

A unique way to address the role of chemokines and their receptors in infectious diseases is to examine the manner in which microbes interact with chemokines and their receptors. Many viruses, particularly those of the herpesvirus and poxvirus families, encode chemokines and chemokine receptor homologues that have been thought to interfere with the action of endogenous chemokines and/or allow viruses to evade host immune responses... 

M-T7 Poxviruses Myxoma virus Resembles IFN7 receptor but binds to and inhibits CXC, CC, and C chemokines with low affinity... 

Table 1. Chemokines, chentokine receptors and chemokine binding proteins encoded by poxviruses...

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