The gene product Murr1 restricts HIV-1 replication in resting CD4(+) lymphocytes

Article

关键词: NF-KAPPA-B;    HUMAN-IMMUNODEFICIENCY-VIRUS;    T-CELLS;    UBIQUITINATION;    ACTIVATION;    ALPHA;    TRANSCRIPTION;    INFECTION;    COMPLEX;    PHOSPHORYLATION;   

DOI  :  10.1038/nature02171

来源: SCIE

【 摘 要 】

Although human immunodeficiency virus-1 (HIV-1) infects quiescent and proliferating CD4(+) lymphocytes, the virus replicates poorly in resting T cells(1-6). Factors that block viral replication in these cells might help to prolong the asymptomatic phase of HIV infection(7); 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 regulation(8,9), 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)-kappaB activity. Knockdown of Murr1 increased NF-kappaB activity and decreased IkappaB-alpha concentrations by facilitating phospho-IkappaB-alpha 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.

【 授权许可】

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