Title: Modest HIV coreceptor function of CXCR3 is strongly enhanced by mimicking the CXCR4 ligand binding pocket in the CXCR3 receptor
Authors: Hatse, Sigrid ×
Huskens, Dana
Princen, Katrien
Vermeire, Kurt
Bridger, Gary J
De Clercq, Erik
Rosenkilde, Mette M
Schwartz, Thue W
Schols, Dominique #
Issue Date: Apr-2007
Publisher: American Society for Microbiology (ASM)
Series Title: Journal of Virology vol:81 issue:7 pages:3632-3639
Abstract: The chemokine receptor CXCR3 can exhibit weak coreceptor function for several 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, coreceptor efficiency of CXCR3 was 100- to >10,000-fold lower as compared to 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 CXCR3[K300A,S304E] receptor showed markedly enhanced HIV coreceptor function as compared to the wild-type receptor (CXCR3[WT]). Moreover, the CXCR4 antagonist AMD3100 exhibited antagonistic and anti-HIV activity in U87.CD4.CXCR3-[K300A,S304E] cells, but not in U87.CD4.CXCR3[WT] cells.
ISSN: 0022-538X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
Laboratory of Experimental Oncology
× corresponding author
# (joint) last author

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