ALTERATIONS IN T4 (CD4) PROTEIN AND MESSENGER-RNA SYNTHESIS IN CELLS INFECTED WITH HIV

ALTERATIONS IN T4 (CD4) PROTEIN AND MESSENGER-RNA SYNTHESIS IN CELLS INFECTED WITH HIV
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DOI:
10.1126/science.3095925
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发表时间:
1986-11-28
期刊:
影响因子:
56.9
通讯作者:
REED, JC
REED, JC
中科院分区:
综合性期刊1区
文献类型:
--
作者:
HOXIE, JA;ALPERS, JD;REED, JC

文献摘要

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感染人类免疫缺陷病毒(HIV)的细胞表面58千道尔顿的T4(CD4)抗原表达降低。在这项研究中,在T细胞系中评估了HIV感染对T4信使核糖核酸(mRNA)和蛋白质产物合成的影响。来自T4⁺细胞系SupT1的代谢标记裂解物用抗T4单克隆抗体进行免疫沉淀。与未感染细胞相比,HIV感染的Sup - T1细胞中与120千道尔顿的病毒包膜和150千道尔顿的包膜前体分子共沉淀的T4量减少。在所研究的五个产生HIV的T细胞系中的四个中,T4 mRNA的稳态水平也降低。因此,HIV感染细胞上T4抗原的减少是由于至少三个因素:T4特异性mRNA的稳态水平降低、可免疫沉淀的T4抗原量减少以及可用的T4抗原与病毒包膜基因产物的复合。数据表明,感染后产生的T4蛋白可能在感染细胞内与病毒包膜基因产物复合。逆转录病毒包膜 - 受体复合物可能因此参与一种普遍机制,通过该机制逆转录病毒的受体在感染后被下调调节,并且细胞功能发生改变。
Cells infected with the human immunodeficiency virus (HIV) show decreased expression of the 58-kilodalton T4 (CD4) antigen on their surface. In this study, the effect of HIV infection on the synthesis of T4 messenger RNA (mRNA) and protein products was evaluated in T-cell lines. Metabolically labeled lysates from the T4+ cell line SupT1 were immunoprecipitated with monoclonal antibodies to T4. Compared with uninfected cells, HIV-infected Sup-T1 cells showed decreased amounts of T4 that coprecipitated with both the 120-kilodalton viral envelope and the 150-kilodalton envelope precursor molecules. In four of five HIV-producing T-cell lines studied, the steady-state levels of T4 mRNA were also reduced. Thus, the decreased T4 antigen on HIV-infected cells is due to at least three factors: reduced steady-state levels of T4-specific mRNA, reduced amounts of immunoprecipitable T4 antigen, and the complexing of available T4 antigen with viral envelope gene products. The data suggested that the T4 protein produced after infection may be complexed with viral envelope gene products within infected cells. Retroviral envelope-receptor complexes may thus participate in a general mechanism by which receptors for retroviruses are down-modulated and alterations in cellular function develop after infection.