Modest human immunodeficiency virus coreceptor function of CXCR3 is strongly enhanced by mimicking the CXCR4 ligand binding pocket in the CXCR3 receptor

Research output: Contribution to journalJournal articleResearchpeer-review

Sigrid Hatse, Dana Huskens, Katrien Princen, Kurt Vermeire, Gary J Bridger, Erik De Clercq, Mette M Rosenkilde, Thue W Schwartz, Dominique Schols

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.
Original languageEnglish
JournalJournal of Virology
Issue number7
Pages (from-to)3632-9
Number of pages7
Publication statusPublished - 2007

Bibliographical 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

ID: 14304927