病毒复制
蛋白酶体
基因敲除
病毒学
生物
病毒
无症状的
基因产物
基因
泛素
化学
分子生物学
细胞生物学
基因表达
医学
遗传学
内科学
作者
Ganesh Lakshmanan,Ezra Burstein,Anuradha Guha-Niyogi,Mark K. Louder,John R. Mascola,Leo W. J. Klomp,Cisca Wijmenga,Colin S. Duckett,Gary J. Nabel
出处
期刊:Nature
[Springer Nature]
日期:2003-12-01
卷期号:426 (6968): 853-857
被引量:225
摘要
Although human immunodeficiency virus-1 (HIV-1) infects quiescent and proliferating CD4+ lymphocytes, the virus replicates poorly in resting T cells1,2,3,4,5,6. Factors that block viral replication in these cells might help to prolong the asymptomatic phase of HIV infection7; however, the molecular mechanisms that control this process are not fully understood. Here we show that Murr1, a gene product known previously for its involvement in copper regulation8,9, inhibits HIV-1 growth in unstimulated CD4+ T cells. This inhibition was mediated in part through its ability to inhibit basal and cytokine-stimulated nuclear factor (NF)-κB activity. Knockdown of Murr1 increased NF-κB activity and decreased IκB-α concentrations by facilitating phospho-IκB-α degradation by the proteasome. Murr1 was detected in CD4+ T cells, and RNA-mediated interference of Murr1 in primary resting CD4+ lymphocytes increased HIV-1 replication. Through its effects on the proteasome, Murr1 acts as a genetic restriction factor that inhibits HIV-1 replication in lymphocytes, which could contribute to the regulation of asymptomatic HIV infection and the progression of AIDS.
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