Modest human immunodeficiency virus coreceptor function of CXCR3 is strongly enhanced by mimicking the CXCR4 ligand binding pocket in the CXCR3 receptor
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Modest human immunodeficiency virus coreceptor function of CXCR3 is strongly enhanced by mimicking the CXCR4 ligand binding pocket in the CXCR3 receptor. / Hatse, Sigrid; Huskens, Dana; Princen, Katrien; Vermeire, Kurt; Bridger, Gary J; De Clercq, Erik; Rosenkilde, Mette M; Schwartz, Thue W; Schols, Dominique.
In: Journal of Virology, Vol. 81, No. 7, 2007, p. 3632-9.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Modest human immunodeficiency virus coreceptor function of CXCR3 is strongly enhanced by mimicking the CXCR4 ligand binding pocket in the CXCR3 receptor
AU - Hatse, Sigrid
AU - Huskens, Dana
AU - Princen, Katrien
AU - Vermeire, Kurt
AU - Bridger, Gary J
AU - De Clercq, Erik
AU - Rosenkilde, Mette M
AU - Schwartz, Thue W
AU - Schols, Dominique
N1 - 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
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
U2 - 10.1128/JVI.01941-06
DO - 10.1128/JVI.01941-06
M3 - Journal article
C2 - 17251291
VL - 81
SP - 3632
EP - 3639
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 7
ER -
ID: 14304927