Yang C, Yang Q, Compans R W
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
J Virol. 2000 Jul;74(13):6217-22. doi: 10.1128/jvi.74.13.6217-6222.2000.
The cytoplasmic tail (R peptide) sequence is able to regulate the fusion activity of the murine leukemia virus (MuLV) envelope (Env) protein. We have previously shown that this sequence exerts a profound inhibitory effect on the fusion activity of simian immunodeficiency virus (SIV)-MuLV chimeric Env proteins which contain the extracellular and transmembrane domains of the SIV Env protein. Recent studies have shown that SIV can utilize several alternative cellular coreceptors for its fusion and entry into the cell. We have investigated the fusion activity of SIV and SIV-MuLV chimeric Env proteins using cells that express different coreceptors. HeLa cells were transfected with plasmid constructs that carry the SIV or SIV-MuLV chimeric Env protein genes and were overlaid with either CEMx174 cells or Ghost Gpr15 cells, which express the Gpr15 coreceptor for SIV, or Ghost CCR5 cells, which express CCR5, an alternate coreceptor for SIV. The R-peptide sequence in the SIV-MuLV chimeric proteins was found to inhibit the fusion with CEMx174 cells or Ghost Gpr15 cells. However, a significant level of fusion was still observed when HeLa cells expressing the chimeric Env proteins were cocultivated with Ghost CCR5 cells. These results show that the R-peptide sequence exerts differential effects on the fusion activity of SIV Env proteins using target cells that express alternative coreceptors.
细胞质尾段（R肽）序列能够调节鼠白血病病毒（MuLV）包膜（Env）蛋白的融合活性。我们之前已经表明，该序列对包含猴免疫缺陷病毒（SIV）Env蛋白胞外和跨膜结构域的SIV-MuLV嵌合Env蛋白的融合活性具有显著抑制作用。最近的研究表明，SIV能够利用几种不同的细胞共受体来实现其融合及进入细胞的过程。我们使用表达不同共受体的细胞研究了SIV和SIV-MuLV嵌合Env蛋白的融合活性。用携带SIV或SIV-MuLV嵌合Env蛋白基因的质粒构建体转染HeLa细胞，然后将其与表达SIV的Gpr15共受体的CEMx174细胞或Ghost Gpr15细胞，或表达SIV的另一种共受体CCR5的Ghost CCR5细胞进行共培养。结果发现，SIV-MuLV嵌合蛋白中的R肽序列能够抑制其与CEMx174细胞或Ghost Gpr15细胞的融合。然而，当表达嵌合Env蛋白的HeLa细胞与Ghost CCR5细胞共培养时，仍能观察到显著水平的融合。这些结果表明，R肽序列对使用表达不同共受体的靶细胞的SIV Env蛋白融合活性具有不同的影响。
