The gene product Murr1 restricts HIV-1 replication in resting CD4+ lymphocytes.
Journal: 2004/January - Nature
ISSN: 1476-4687
Abstract:
Although human immunodeficiency virus-1 (HIV-1) infects quiescent and proliferating CD4+ lymphocytes, the virus replicates poorly in resting T cells. Factors that block viral replication in these cells might help to prolong the asymptomatic phase of HIV infection; 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, 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.
Relations:
Citations
(99)
Chemicals
(8)
Genes
(8)
Organisms
(2)
Processes
(3)
Anatomy
(2)
Affiliates
(1)
Similar articles
Articles by the same authors
Discussion board
Collaboration tool especially designed for Life Science professionals.Drag-and-drop any entity to your messages.