Virally encoded chemokines and chemokine receptors in the role of viral infections.
Large DNA viruses such as pox- and in particular herpesviruses are notorious in their ability to evade the immune system and to be maintained in the general population. Based on the accumulated knowledge reviewed in this study it is evident that important mechanisms of these actions are the acquisition and modification of host-encoded chemokines and chemokine receptors. The described viral molecules leave nothing to chance and have thoroughly and efficiently corrupted the host immune system. Through this process viruses have identified key molecules in antiviral responses by their inhibition of these or potent ways to alter an efficient antiviral response to a weak Th2-driven response. Examples here are the chemokine scavenging by US28, attractance of Th2 cells and regulatory cells by vMIP1-3 and the selective engaging of CCR8 by MC148. Important insights into viral pathology and possible targets for antiviral therapies have been provided by UL33, UL78 and in particular ORF74 and the chances are that many more will follow. In HHV8 vMIP-2 and the chemokine-binding proteins potent anti-inflammatory agents have been provided. These have already had their potential demonstrated in animal models and may in their native or modified forms represent useful therapies in humans.
Holst
Peter J
PJ
Laboratory for Molecular Pharmacology, Department of Pharmacology, Panum Institute, Copenhagen, Denmark.
Lüttichau
Hans R
HR
Schwartz
Thue W
TW
Rosenkilde
Mette M
MM
D000818:Animals; D018925:Chemokines / Q000494:pharmacology*; D004267:DNA Viruses / Q000276:immunology / Q000378:metabolism; D006564:Herpesviridae / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D008322:Mammals; D011213:Poxviridae Infections / Q000276:immunology*; D019707:Receptors, Chemokine / Q000378:metabolism*; D011991:Receptors, Virus / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000494:pharmacology*
D018925:Chemokines; D019707:Receptors, Chemokine; D011991:Receptors, Virus; D014764:Viral Proteins