| Genotypic coreceptor analysis. | |
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MedLine Citation:
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PMID: 17933727 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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HIV infects target cells by binding of its envelope gp120 protein to CD4 and a coreceptor on the cell surface. In vivo, the different HIV-strains use either CCR5 or CXCR4 as coreceptor. CCR5-using strains are named R5 viruses, while CXCR4-using strains are named X4. X4 viruses usually occur in the later stages. Coreceptor usage is a marker for disease progression. Additionally interest on coreceptors continually raises as a consequence of the development of a new class of antiretroviral drugs, namely the coreceptor antagonists or blockers. These specific drugs block the CCR5 or the CXCR4 coreceptors. So far, the CXCR4 blockers are not allowed to be used in the clinical practice due to their severe side effects. On the other hand, CCR5 blockers are currently in clinical practice, although they can only be administered after a baseline determination of the coreceptor usage of the predominant viral strain. Most of the coreceptor analyses in clinical cohorts have been performed with commercially available phenotypic assays. As for resistance testing of NRTIs, NNRTIs and PIs, efforts have also been made to predict the coreceptor usage from the genotype of the viruses. Different rules have been published based on the amino acid sequence of the Env-V3 region of HIV-gp120, which is known to be the major determinant of coreceptor usage. Among these, the most widely used is the 11/25 rule. Recently, bioinformatics driven prediction systems have been developed. Three of the interpretation systems are freely available via internet: WetCat, WebPSSM, geno2pheno[coreceptor]. All three systems focus on the Env-V3 region and take the amino acid sequence only into account. They learn from phenotypic and corresponding genotypic data. So far, two cohorts have been analyzed with such a genotypic approach and provided frequencies of R5 virus strains that are within the range of those reported with phenotypic assays. For one of the systems, geno2pheno[coreceptor], additional clinical data (e.g. CD4+T-cell counts) or structural information can be used to improve the prediction. Such genotypic systems provide the possibility for rapid screening of patients who may be administered with CCR5 blockers like the recently licensed Maraviroc. |
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Authors:
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S Sierra; R Kaiser; A Thielen; T Lengauer |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: European journal of medical research Volume: 12 ISSN: 0949-2321 ISO Abbreviation: Eur. J. Med. Res. Publication Date: 2007 Oct |
Date Detail:
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Created Date: 2007-10-15 Completed Date: 2007-12-26 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9517857 Medline TA: Eur J Med Res Country: Germany |
Other Details:
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Languages: eng Pagination: 453-62 Citation Subset: IM |
Affiliation:
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Institut für Virologie der Universität zu Köln, Fürst Pückler Str. 56, 50935 Köln, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Anti-HIV Agents / pharmacology, therapeutic use* Drug Resistance, Viral / genetics* HIV Envelope Protein gp120 / chemistry, genetics, physiology HIV Infections / drug therapy*, virology HIV-1 / classification, drug effects*, genetics Humans Molecular Sequence Data Prognosis Receptors, CCR5 / antagonists & inhibitors, genetics*, physiology Receptors, CXCR4 / antagonists & inhibitors, genetics*, physiology Software* |
| Chemical | |
Reg. No./Substance:
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0/Anti-HIV Agents; 0/HIV Envelope Protein gp120; 0/Receptors, CCR5; 0/Receptors, CXCR4 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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