PHYSICOCHEMICAL DISSOCIATION OF CD4-MEDIATED SYNCYTIUM FORMATION AND SHEDDING OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP120
PHYSICOCHEMICAL DISSOCIATION OF CD4-MEDIATED SYNCYTIUM FORMATION AND SHEDDING OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP120
复制标题
DOI：
10.1128/jvi.67.7.3818-3825.1993
复制
发表时间：
1993-07-01
影响因子：
5.4
通讯作者：
BUGELSKI, PJ
中科院分区：
文献类型：
--
作者：
FU, YK;HART, TK;BUGELSKI, PJ
活化的人类免疫缺陷病毒1型(HIV-1)gp41介导的CD4融合的机制以及可溶性CD4(SCD4)诱导gp120脱落的生物学意义尚不清楚。这些研究的目的是确定gp120的脱落是否导致融合激活或失活。以稳定表达HIV-1包膜糖蛋白(gp120-gp41复合体)的BJAB细胞(TF228.1.16)为研究对象，研究了pH和温度对sCD4诱导的gp120脱落和与CD4+SupT1细胞融合(合胞体形成)的影响。SCD4诱导的gp120脱落在pH 4.5~5.5时最大，在pH 8.5时不发生。在生理pH下，sCD4诱导的gp120在22℃、37℃和40℃发生脱落，但在16℃和4℃都没有。相反，合胞体在pH 8.5(最大pH 7.5)时形成，但在pH 4.5~5.5之间不形成合胞体。在pH 7.5时，合胞体在37℃和40℃时形成，但在22℃、16℃或4℃时不形成合胞体。TF228.1.16和SupT1细胞在转变到37℃之前，在4、16或22℃预孵育后，合胞体的形成分别与对照组相似、增加或减少。此外，CD4-gp120-gp41三元复合体的活性中间体可以在16摄氏度形成；这种中间体在转变到37摄氏度时迅速执行融合，但在转变到22摄氏度的脱落式允许但不允许融合的温度时很容易衰变。这些物理化学数据表明，HIV-1 gp120的脱落不是融合级联过程中不可或缺的步骤，CD4可能在类似于sCD4诱导的gp120脱落的过程中使融合复合体失活。
The mechanism of CD4-mediated fusion via activated human immunodeficiency virus type 1 (HIV-1) gp41 and the biological significance of soluble CD4 (sCD4)-induced shedding of gp120 are poorly understood. The purpose of these investigations was to determine whether shedding of gp120 led to fusion activation or inactivation. BJAB cells (TF228.1.16) stably expressing HIV-1 envelope glycoproteins (the gp120-gp41 complex) were used to examine the effects of pH and temperature on sCD4-induced shedding of gp120 and on cell-to-cell fusion (syncytium formation) with CD4+ SupT1 cells. sCD4-induced shedding of gp120 was maximal at pH 4.5 to 5.5 and did not occur at pH 8.5. At physiologic pH, sCD4-induced shedding of gp120 occurred at 22, 37, and 40-degrees-C but neither at 16 nor 4-degrees-C. In contrast, syncytia formed at pH 8.5 (maximally at pH 7.5) but not at pH 4.5 to 5.5. At pH 7.5, syncytia formed at 37 and 40-degrees-C but not at 22, 16, or 4-degrees-C. Preincubation of cocultures of TF228.1.16 and SupT1 cells at 4, 16, or 22-degrees-C before the shift to 37-degrees-C resulted in similar, increased, or decreased syncytium formation, respectively, compared with the control. Furthermore, an activated intermediate of CD4-gp120-gp41 ternary complex may form at 16-degrees-C; this intermediate rapidly executes fusion upon a shift to 37-degrees-C but readily decays upon a shift to the shedding-permissive but fusion-nonpermissive temperature of 22-degrees-C. These physicochemical data indicate that shedding of HIV-1 gp120 is not an integral step in the fusion cascade and that CD4 may inactivate the fusion complex in a process analogous to sCD4-induced shedding of gp120.