@article{70316cb09d2d11debc73000ea68e967b,
title = "Modest human immunodeficiency virus coreceptor function of CXCR3 is strongly enhanced by mimicking the CXCR4 ligand binding pocket in the CXCR3 receptor",
abstract = "The chemokine receptor CXCR3 can exhibit weak coreceptor function for several human immunodeficiency virus type 1 (HIV-1) and HIV-2 strains and clinical isolates. These viruses produced microscopically visible cytopathicity in U87.CD4.CXCR3 cell cultures, whereas untransfected (CXCR3-negative) U87.CD4 cells remained uninfected. Depending on the particular virus, the coreceptor efficiency of CXCR3 was 100- to >10,000-fold lower compared to that of CXCR4. A CXCR3 variant carrying the CXCR4 binding pocket was constructed by simultaneous lysine-to-alanine and serine-to-glutamate substitutions at positions 300 and 304 of the CXCR3 receptor. This mutant receptor (CXCR3[K300A, S304E]) showed markedly enhanced HIV coreceptor function compared to the wild-type receptor (CXCR3[WT]). Moreover, the CXCR4 antagonist AMD3100 exhibited antagonistic and anti-HIV activities in U87.CD4.CXCR3[K300A, S304E] cells but not in U87.CD4.CXCR3[WT] cells.",
author = "Sigrid Hatse and Dana Huskens and Katrien Princen and Kurt Vermeire and Bridger, {Gary J} and {De Clercq}, Erik and Rosenkilde, {Mette M} and Schwartz, {Thue W} and Dominique Schols",
note = "Keywords: Amino Acid Sequence; Binding Sites; Cell Line, Tumor; HIV; Humans; Ligands; Molecular Mimicry; Molecular Sequence Data; Receptors, CXCR3; Receptors, CXCR4; Receptors, Chemokine; Receptors, HIV",
year = "2007",
doi = "10.1128/JVI.01941-06",
language = "English",
volume = "81",
pages = "3632--9",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "7",
}
