Current Drug Targets

Francis J. Castellino
Kleiderer-Pezold Professor of Biochemistry
Director, W.M. Keck Center for Transgene Research
Dean Emeritus, College of Science
230 Raclin-Carmichael Hall, University of Notre Dame
Notre Dame, IN 46556


Targeting Herpesvirus Reliance of the Chemokine System

Author(s): Mette M. Rosenkilde and Thomas N. Kledal

Affiliation: Laboratory for Molecular Pharmacology, Department of Pharmacology, Panum Institute, University of Copenhagen, Copenhagen, Denmark and 2 Clinical Research Unit, Copenhagen University Hospital Hvidovre, Denmark;


Viral infections depend on an intimate relationship between the infectious agent and the host cells. Viruses need the host cells for replication, while the innate- and adaptive- immunesystem of the host is fighting to kill the infected cell in order to clear out the pathogen and survive the infection. However, since both virus and host exist, the organisms struggle must reach an ecological equilibrium. Among the best-studied interactions between viruses and the host immune system are those between herpesviruses and their hosts. Herpesviruses are known to devote a significant part of their large genomes on immuno-modulatory genes, some encoding chemokines or chemokine receptors. These genes, which may be dispensable for viral replication in vitro, are highly important for viral growth in vivo, for viral dissemination and disease progression. Indeed, all β- and γ-herpesviruses have acquired homologs of both chemokines and chemokine receptors belonging to the 7 transmembrane (7TM) spanning, G protein-coupled receptor family. 7TM receptors are very efficient drug targets and are currently the most popular class of investigational drug targets. A notable trait for the virus encoded chemokine receptors seems to be their constitutive activity. The biological function of the constitutive activity is still unclear, but it has become clear that the receptors are involved in important parts of the viral lifecycle in vivo, and that the receptor signaling is involved in γ-herpesvirus mediated cell transformation. Therefore, blocking the signaling of these receptors will provide an efficient and highly specific way to inhibit viral replication in vivo and disease progression in the hosts.

Keywords: Mammalian herpesviruses, AIDS, replication cycle, CXC-chemokine, Scavenger, Drug targets

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Article Details

Page: [103 - 118]
Pages: 16
DOI: 10.2174/138945006775270259