CD4-independent entry and replication of simian immunodeficiency virus in primary rhesus macaque astrocytes are regulated by the transmembrane protein.
CD4-independent entry and replication of simian immunodeficiency virus in primary rhesus macaque astrocytes are regulated by the transmembrane protein.
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猿猴免疫缺陷病毒在原代恒河猴星形胶质细胞中的 CD4 依赖性进入和复制受到跨膜蛋白的调节。
DOI：
10.1128/jvi.79.8.4944-4951.2005
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发表时间：
2005
影响因子：
5.4
通讯作者：
Clements,JaniceE
中科院分区：
文献类型：
--
作者：
Overholser,EmilyD;Babas,Tahar;Zink,MChristine;Barber,SheilaA;Clements,JaniceE
先前的研究表明，猿猴免疫缺陷病毒（SIV）神经毒力的遗传决定因素映射到envandnegenes。我们实验室最近的研究表明，SIV在恒河猴星形细胞培养中的复制依赖于该基因。在这里，我们证明巨噬细胞的趋向性并不足以在星形胶质细胞中进行复制，Env的跨膜部分（TM）中的特定氨基酸对星形胶质细胞中SIV的最佳复制也很重要。具体来说，要在这些细胞中进行有效的复制，需要在751个氨基酸位置上添加一个甘氨酸和截断TM的细胞质尾部。利用可溶性CD4细胞进行的研究表明，TM蛋白内的这些变化调节了依赖CD4或ccr5的病毒进入星形胶质细胞。此外，我们观察到两种不同的CD4独立的神经侵袭性SIV/DeltaB670菌株也在星形胶质细胞中高效复制，进一步支持CD4独立性在体外和体内作为SIV感染星形胶质细胞的重要决定因素的作用。
Previous studies have demonstrated that the genetic determinants of simian immunodeficiency virus (SIV) neurovirulence map to theenvandnefgenes. Recent studies from our laboratory demonstrated that SIV replication in primary rhesus macaque astrocyte cultures is dependent upon thenefgene. Here, we demonstrate that macrophage tropism is not sufficient for replication in astrocytes and that specific amino acids in the transmembrane (TM) portion of Env are also important for optimal SIV replication in astrocytes. Specifically, a Gly at amino acid position 751 and truncation of the cytoplasmic tail of TM are required for efficient replication in these cells. Studies using soluble CD4 demonstrated that these changes within the TM protein regulate CD4-independent, CCR5-dependent entry of virus into astrocytes. In addition, we observed that two distinct CD4-independent, neuroinvasive strains of SIV/DeltaB670 also replicated efficiently in astrocytes, further supporting the role of CD4 independence as an important determinant of SIV infection of astrocytes in vitro and in vivo.