Cell surface CD4 downregulation and resistance to superinfection induced by a defective provirus of HIV-1.
Cell surface CD4 downregulation and resistance to superinfection induced by a defective provirus of HIV-1.
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DOI：
10.1006/viro.1994.1683
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发表时间：
1994-12
期刊：
影响因子：
3.7
通讯作者：
S. Little;N. L. Riggs;M. Chowers;N. Fitch;D. Richman;C. Spina;J. Guatelli
中科院分区：
文献类型：
--
作者：
S. Little;N. L. Riggs;M. Chowers;N. Fitch;D. Richman;C. Spina;J. Guatelli
先前已在感染者中检测到编码HIV-1调节基因缺陷的前病毒序列；然而，这些缺陷基因组在发病机制中的作用尚不清楚。这种复制缺陷的基因组可能会导致HIV-1细胞受体(CD4)下调的假设得到了检验。将含有REV编码序列5‘剪接点突变的前病毒稳定地转染CEM细胞。这个突变体表达早期的HIV-1mRNAs，但复制有缺陷。表达这种缺陷前病毒的细胞表面CD4明显减少。这种对CD4的下调依赖于完整的nef基因，足以产生对野生型病毒重叠感染的抵抗力。这些发现表明，复制缺陷HIV-1表达的Nef可以下调CD4。T淋巴细胞膜的这种扰动是缺陷HIV-1致病的潜在基础。
Proviral sequences encoding defective HIV-1 regulatory genes have been detected previously in infected individuals; however, the role of these defective genomes in pathogenesis is unclear. The hypothesis that such replication-defective genomes might induce downregulation of the cellular receptor for HIV-1 (CD4) was tested. CEM cells were stably transfected with a provirus that contains a mutation in the splice site immediately 5' of the rev coding sequence. This mutant expresses early HIV-1 mRNAs but is defective for replication. Cells expressing this defective provirus displayed markedly reduced surface CD4. This downregulation of CD4 was dependent on an intact nef gene and was sufficient to cause resistance to superinfection by wild-type virus. These findings indicate that Nef as expressed by replication-defective HIV-1 can downregulate CD4. This perturbation of the T lymphocyte cell membrane is a potential basis for pathogenicity of defective HIV-1.