Schols D, De Clercq E
Laboratory of Experimental Chemotherapy, Rega Institute for Medical Research, Leuven, Belgium.
J Gen Virol. 1998 Sep;79 ( Pt 9):2203-5. doi: 10.1099/0022-1317-79-9-2203.
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.
从一只山魈身上分离出的猿猴免疫缺陷病毒(SIV)mnd(GB - 1)毒株,可在人T细胞系CEM细胞中复制,并受到CXC趋化因子基质细胞衍生因子1α和1β(SDF - 1α/SDF - 1β)的抑制,SDF - 1α/SDF - 1β是CXCR4的天然配体。其半数抑制浓度(IC50)约为70 - 80 ng/ml,这与SDF - 1α/SDF - 1β对T嗜性1型人类免疫缺陷病毒(HIV - 1)和HIV - 2的IC50相当。特异性抗CXCR4单克隆抗体12G5以1μg/ml的IC50抑制SIVmnd的复制。此外,特异性CXCR4拮抗剂双环胺AMD3100对SIVmnd的IC50为8 ng/ml,与其对T嗜性HIV - 1和HIV - 2毒株的IC50相当。另外两种SIV毒株SIVagm3和SIVmac251对SDF - 1α/SDF - 1β、抗CXCR4单克隆抗体和AMD3100不敏感。SIVmnd仅在表达CXCR4的HOS.CD4细胞中复制,而不在表达CCR1、CCR2b、CCR3、CCR4或CCR5的HOS.CD4转染细胞中复制。据我们所知,这是首个被发现以CXCR4而非CCR5作为进入人类细胞主要共受体的SIV毒株。