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      The role of CCR5 in HCV infection

      review-article
      Author(s): 1 , 1 ,
      Publication date (Electronic):
      Journal: European Journal of Medical Research
      Publisher: BioMed Central
      Keywords: chemokine, chemokine receptor, CCR5, HCV, immune response

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          Abstract

          Efficient recruitment and activation of immuno-competent cells is crucial for an effective immune response to hepatitis C virus (HCV) infection. Chemokines and chemokine receptors have been shown to be critically involved in these processes.

          The CCR5 chemokine receptor is expressed on several cells of the immune system and has been suggested to influence the susceptibility to HCV infection as well as natural course and progression of hepatitis C. However, these reports are still controversial.

          This review will summarize and discuss the available data regarding the potential role of CCR5 and its ligands in hepatitis C.

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          Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study.

          M. Dean, M. Carrington, C. Winkler … (1996)
          The chemokine receptor 5 (CKR5) protein serves as a secondary receptor on CD4(+) T lymphocytes for certain strains of human immunodeficiency virus-type 1 (HIV-1). The CKR5 structural gene was mapped to human chromosome 3p21, and a 32-base pair deletion allele (CKR5Delta32) was identified that is present at a frequency of approximately0.10 in the Caucasian population of the United States. An examination of 1955 patients included among six well-characterized acquired immunodeficiency syndrome (AIDS) cohort studies revealed that 17 deletion homozygotes occurred exclusively among 612 exposed HIV-1 antibody-negative individuals (2.8 percent) and not at all in 1343 HIV-1-infected individuals. The frequency of CKR5 deletion heterozygotes was significantly elevated in groups of individuals that had survived HIV-1 infection for more than 10 years, and, in some risk groups, twice as frequent as their occurrence in rapid progressors to AIDS. Survival analysis clearly shows that disease progression is slower in CKR5 deletion heterozygotes than in individuals homozygous for the normal CKR5 gene. The CKR5Delta32 deletion may act as a recessive restriction gene against HIV-1 infection and may exert a dominant phenotype of delaying progression to AIDS among infected individuals.
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            Chemokines and disease.

            Craig Gerard, Barrett Rollins (2001)
            We examine here several diseases that are associated with inappropriate activation of the chemokine network. Detailed comment has been restricted to pathological states for which there are compelling data either from clinical observations or animal models. These include cardiovascular disease, allergic inflammatory disease, transplantation, neuroinflammation, cancer and HIV-associated disease. Discussion focuses on therapeutic directions in which the rapidly evolving chemokine field appears to be headed.
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              International union of pharmacology. XXII. Nomenclature for chemokine receptors.

              P Murphy, M Baggiolini, I Charo … (2000)
              Chemokine receptors comprise a large family of seven transmembrane domain G protein-coupled receptors differentially expressed in diverse cell types. Biological activities have been most clearly defined in leukocytes, where chemokines coordinate development, differentiation, anatomic distribution, trafficking, and effector functions and thereby regulate innate and adaptive immune responses. Pharmacological analysis of chemokine receptors is at an early stage of development. Disease indications have been established in human immunodeficiency virus/acquired immune deficiency syndrome and in Plasmodium vivax malaria, due to exploitation of CCR5 and Duffy, respectively, by the pathogen for cell entry. Additional indications are emerging among inflammatory and immunologically mediated diseases, but selection of targets in this area still remains somewhat speculative. Small molecule antagonists with nanomolar affinity have been reported for 7 of the 18 known chemokine receptors but have not yet been studied in clinical trials. Virally encoded chemokine receptors, as well as chemokine agonists and antagonists, and chemokine scavengers have been identified in medically important poxviruses and herpesviruses, again underscoring the importance of the chemokine system in microbial pathogenesis and possibly identifying specific strategies for modulating chemokine action therapeutically. The purpose of this review is to update current concepts of the biology and pharmacology of the chemokine system, to summarize key information about each chemokine receptor, and to describe a widely accepted receptor nomenclature system, ratified by the International Union of Pharmacology, that is facilitating clear communication in this area.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Eur J Med Res
                Journal ID (iso-abbrev): Eur. J. Med. Res
                Title: European Journal of Medical Research
                Publisher: BioMed Central
                ISSN (Print): 0949-2321
                ISSN (Electronic): 2047-783X
                Publication date Collection: 2010
                Publication date (Electronic): 30 March 2010
                Volume: 15
                Issue: 3
                Pages: 97-101
                Affiliations
                [1 ]Department of Internal Medicine I, University of Bonn, Bonn, Germany
                Article
                Publisher ID: 2047-783X-15-3-97
                DOI: 10.1186/2047-783X-15-3-97
                PMC ID: 3352223
                PubMed ID: 20452893
                SO-VID: d59317bf-8bb1-4069-8460-401ddda473d8
                Copyright © Copyright ©2010 I. Holzapfel Publishers
                History
                Date received : 12 February 2010
                Date accepted : 12 March 2010
                Categories
                Subject: Review

                ScienceOpen disciplines: Medicine
                Keywords: hcv,ccr5,chemokine receptor,immune response,chemokine
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: hcv, ccr5, chemokine receptor, immune response, chemokine

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