Little S J, Riggs N L, Chowers M Y, Fitch N J, Richman D D, Spina C A, Guatelli J C
Department of Medicine, University of California at San Diego.
Virology. 1994 Dec;205(2):578-82. doi: 10.1006/viro.1994.1683.
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.
先前在受感染个体中已检测到编码缺陷型HIV-1调控基因的前病毒序列；然而，这些缺陷基因组在发病机制中的作用尚不清楚。本研究对这类复制缺陷型基因组可能诱导HIV-1细胞受体（CD4）下调的假说进行了验证。用一种前病毒稳定转染CEM细胞，该前病毒在rev编码序列5'端紧邻的剪接位点存在突变。这种突变体可表达早期HIV-1 mRNA，但复制存在缺陷。表达这种缺陷前病毒的细胞表面CD4明显减少。CD4的这种下调依赖于完整的nef基因，并且足以导致对野生型病毒超感染的抗性。这些发现表明，由复制缺陷型HIV-1表达的Nef可下调CD4。T淋巴细胞细胞膜的这种扰动是缺陷型HIV-1致病性的潜在基础。
