Abstract
Human herpesviruses (HHVs) are widespread pathogens involved in proliferative diseases, inflammatory conditions, and cardiovascular diseases. During evolution, homologs of human chemokine receptors were integrated into the HHV genomes. In addition to binding endogenous chemokines, these viral G protein-coupled receptors (vGPCRs) have acquired the ability to signal in a constitutive manner. Ligand-induced and ligand-independent and autocrine and paracrine signaling properties of vGPCRs modify the functions of the expressing cells and lead to transformation and escape from immune surveillance. Furthermore, cross-talk or heterodimerization with endogenous chemokine receptors represent other ways for vGPCRs to modify intracellular signaling and cellular functions. As such, these viral receptors seem to play a prominent role during viral pathogenesis and life cycle and thus represent innovative antiviral therapies.
- GPCR, G protein-coupled receptor
- vGPCR, viral G protein-coupled receptor
- CMV, cytomegalovirus
- COX-2, cyclooxygenase-2
- CREB, cAMP-responsive element binding protein
- EBV, Epstein-Barr virus
- FAK, focal adhesion kinase
- HCMV, human cytomegalovirus
- HHV, human herpesvirus
- KS, Kaposi's sarcoma
- KSHV, Kaposi's sarcoma associated virus
- VEGF, vascular endothelial growth factor
- MAPK, mitogen-activated protein kinase
- NF-κB, nuclear factor κB
- PI3K, phosphatidylinositol phosphate 3-kinase
- mTOR, mammalian target of rapamycin
- TSC, tuberous sclerosis complex
- PKR, RNA-dependent protein kinase
- WT, wild type
- PGE2, prostaglandin E2
- PI-103, 3-[4-(4-morpholinyl)pyrido[3′,2′:4,5]furo[3,2-d]pyrimidin-2-yl]-phenol
- Bay 11-7082, (E)-3-(4-methylphenylsulfonyl)-2-propenenitrile
- VUF2274, 4-(4-chlorophenyl)-4-hydroxy-a,a-diphenyl-1-piperidinepentanenitrile hydrochloride.
Footnotes
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This work was supported by the Dutch Organization for Scientific Research NWO [Vidi Grant 700.54.425 and Veni Grant 700.55.403]. The authors declare no financial conflict of interest.
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Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.
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ABBREVIATIONS:
- Received April 17, 2009.
- Accepted June 25, 2009.
- © 2009 The American Society for Pharmacology and Experimental Therapeutics
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