The simian immunodeficiency virus mnd(GB-1) strain uses CXCR4, not CCR5, as coreceptor for entry in human cells.
The simian immunodeficiency virus (SIV) mnd(GB-1) strain, isolated from a mandrill, replicates in a human T cell line, CEM cells, and is inhibited by the CXC-chemokines, stromal cell-derived factor 1alpha and 1beta (SDF-1alpha/SDF-1beta), the natural ligands for CXCR4. The IC50 was around 70-80 ng/ml, which corresponds to the IC50 of SDF-1alpha/SDF-1beta for T-tropic human immunodeficiency virus type 1 (HIV-1) and HIV-2. The specific anti-CXCR4 MAb 12G5 inhibited replication of SIVmnd at an IC50 of 1 microg/ml. Also, the IC50 of 8 ng/ml for SIVmnd of the bicyclam AMD3100, a specific CXCR4 antagonist, is comparable with its IC50 for T-tropic HIV-1 and HIV-2 strains. Two other SIV strains, SIVagm3 and SIVmac251, were insensitive to SDF-1alpha/SDF-1beta, anti-CXCR4 MAb and AMD3100. SIVmnd replicates only in HOS.CD4 cells expressing CXCR4 and not in HOS.CD4 transfectants expressing CCR1, CCR2b, CCR3, CCR4 or CCR5. This is, to our knowledge, the first SIV strain found to use CXCR4 and not CCR5 as a main coreceptor for entering human cells.
Schols
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Laboratory of Experimental Chemotherapy, Rega Institute for Medical Research, Leuven, Belgium. Dominique.Schols@rega.kuleuven.ac.be
De Clercq
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001596:Benzylamines; D002460:Cell Line; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D000080027:Cyclams; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology; D015498:HIV-2 / Q000472:pathogenicity / Q000502:physiology; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D010215:Papio / Q000821:virology; D019713:Receptors, CCR5 / Q000502:physiology; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000502:physiology*; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology*; D014162:Transfection; D014779:Virus Replication / Q000187:drug effects
D000911:Antibodies, Monoclonal; D001596:Benzylamines; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; C088327:plerixafor