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Author, Editor(s)

Author(s):

Sierra, Saleta
Kaiser, Rolf
Thielen, Alexander
Lengauer, Thomas

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Not MPG Author(s):

Sierra, Saleta
Kaiser, Rolf

BibTeX cite key*:

Sierra2006

Title

Title*:

Genotypic coreceptor analysis.

Journal

Journal Title*:

European Journal of Medical Research

Journal's URL:


Download URL
for the article:

http://maraviroc.de/fileadmin/content/pdfs/Sierra_2007_01.pdf

Language:

English

Publisher

Publisher's
Name:

Holzapfel

Publisher's URL:


Publisher's
Address:

Harthauser Strasse 105, 81545 München

ISSN:

0949-2321

Vol, No, pp, Date

Volume*:

12

Number:

9

Publishing Date:

October 2007

Pages*:

453-462

Number of
VG Pages:


Page Start:


Page End:


Sequence Number:


DOI:


Note, Abstract, ©

Note:


(LaTeX) Abstract:

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.

URL for the Abstract:


Categories,
Keywords:

HIV, Coreceptor, Tropism, Prediction, Genotype, Entry

HyperLinks / References / URLs:


Copyright Message:


Personal Comments:


Download
Access Level:

Internal

Correlation

MPG Unit:

Max-Planck-Institut für Informatik



MPG Subunit:

Computational Biology and Applied Algorithmics

Audience:

experts only

Appearance:

MPII WWW Server, MPII FTP Server, MPG publications list, university publications list, working group publication list, Fachbeirat, VG Wort


BibTeX Entry:

@ARTICLE{Sierra2006,
AUTHOR = {Sierra, Saleta and Kaiser, Rolf and Thielen, Alexander and Lengauer, Thomas},
TITLE = {Genotypic coreceptor analysis.},
JOURNAL = {European Journal of Medical Research},
PUBLISHER = {Holzapfel},
YEAR = {2007},
NUMBER = {9},
VOLUME = {12},
PAGES = {453--462},
ADDRESS = {Harthauser Strasse 105, 81545 M{\"u}nchen},
MONTH = {October},
ISBN = {0949-2321},
}


Entry last modified by Alexander Thielen, 02/28/2008
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Editor(s)
Alexander Thielen
Created
12/12/2007 03:50:16 PM
Revision
0.



Editor
Alexander Thielen



Edit Date
12/12/2007 03:50:17 PM