Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Virology, PROTEIN-COUPLED RECEPTOR, CHEMOKINE RECEPTOR, HIV-1 ENTRY, MONOCLONAL-ANTIBODY, T-CELLS, INHIBITION, STRAINS, FUSION, CCR5, INFECTION, Amino Acid Sequence, Binding Sites, Cell Line, Tumor, HIV, Humans, Ligands, Molecular Mimicry, Molecular Sequence Data, Receptors, CXCR3, Receptors, CXCR4, Receptors, Chemokine, Receptors, HIV, 06 Biological Sciences, 07 Agricultural and Veterinary Sciences, 11 Medical and Health Sciences, 30 Agricultural, veterinary and food sciences, 31 Biological sciences, 32 Biomedical and clinical sciences

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.