Primary, syncytium-inducing human immunodeficiency virus type 1 isolates are dual-tropic and most can use either Lestr or CCR5 as coreceptors for virus entry
Primary, syncytium-inducing human immunodeficiency virus type 1 isolates are dual-tropic and most can use either Lestr or CCR5 as coreceptors for virus entry
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DOI：
10.1128/jvi.70.12.8355-8360.1996
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发表时间：
1996-12
影响因子：
5.4
通讯作者：
G. Simmons;D. Wilkinson;J. Reeves;M. Dittmar;S. Beddows;J. Weber;G. Carnegie;U. Desselberger;P. Gray;R. Weiss;P. Clapham
中科院分区：
文献类型：
--
作者：
G. Simmons;D. Wilkinson;J. Reeves;M. Dittmar;S. Beddows;J. Weber;G. Carnegie;U. Desselberger;P. Gray;R. Weiss;P. Clapham
一组原代合胞体诱导(SI)人类免疫缺陷病毒1型分离株感染了几个CD4+T细胞系，包括MT-2和C8166，测试了它们对血源性巨噬细胞的感染情况。对C8166细胞和巨噬细胞的感染性滴度表明，SI原代毒株感染巨噬细胞的效率远高于T细胞系适应的HIV-1毒株，如LAI和RF。因此，这些初级SI毒株是双嗜性的。用有限稀释法制备的两株SI株的9个生物学克隆的巨噬细胞/C8166感染力比率与其亲本病毒相似，表明这种双嗜性表型不是由于非SI/巨噬细胞嗜性病毒和SI/T细胞嗜性病毒的混合所致。我们测试了原代SI株是否使用LestR(Fusin)或CCR5作为辅助受体。瞬时表达LestR的CAT CCC/CD4细胞感染支持包括LAI在内的T细胞系适应株的感染，而表达CCR5的CCC/CD4细胞对原代非SI株以及分子克隆株SF-162和Jr-CSF敏感。几个SI原代毒株以及分子克隆的双嗜性病毒89.6和GUN-1感染了LestR+和CCR5+的CCC/CD4细胞。因此，这些病毒可以在LestR和CCR5之间选择进入细胞。有趣的是，一些感染LestR+细胞的双嗜性原代SI株未能感染CCR5+细胞，这表明这些病毒可能使用替代的辅助受体来感染巨噬细胞。或者，CCR5可以在CAT细胞上以不同的方式处理或呈现，从而影响某些原代SI菌株的进入，但不影响其他菌株的进入。
A panel of primary syncytium-inducing (SI) human immunodeficiency virus type 1 isolates that infected several CD4+ T-cell lines, including MT-2 and C8166, were tested for infection of blood-derived macrophages. Infectivity titers for C8166 cells and macrophages demonstrated that primary SI strains infected macrophages much more efficiently than T-cell line-adapted HIV-1 strains such as LAI and RF. These primary SI strains were therefore dual-tropic. Nine biological clones of two SI strains, prepared by limiting dilution, had macrophage/C8166 infectivity ratios similar to those of their parental viruses, indicating that the dual-tropic phenotype was not due to a mixture of non-SI/macrophage-tropic and SI/T-cell tropic viruses. We tested whether the primary SI strains used either Lestr (fusin) or CCR5 as coreceptors. Infection of cat CCC/CD4 cells transiently expressing Lestr supported infection by T-cell line-adapted strains including LAI, whereas CCC/CD4 cells expressing CCR5 were sensitive to primary non-SI strains as well as to the molecularly cloned strains SF-162 and JR-CSF. Several primary SI strains, as well as the molecularly cloned dual-tropic viruses 89.6 and GUN-1, infected both Lestr+ and CCR5+ CCC/CD4 cells. Thus, these viruses can choose between Lestr and CCR5 for entry into cells. Interestingly, some dual-tropic primary SI strains that infected Lestr+ cells failed to infect CCR5+ cells, suggesting that these viruses may use an alternative coreceptor for infection of macrophages. Alternatively, CCR5 may be processed or presented differently on cat cells so that entry of some primary SI strains but not others is affected.