Background:  Although HIV-1 infects quiescent and proliferating CD4⁺ lymphocytes, the virus replicates poorly in resting T cells. Factors that block viral replication in these cells may help to prolong the asymptomatic phase of HIV infection; however, the molecular mechanisms that control this process are not fully understood.

Results:  In this study, we report 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 NF-kB activity. Knock-down of Murr1 increased NF-kB activity and decreased IkB-a levels by facilitating phospho-IkB-a degradation by the proteasome. Murr1 was detected in CD4⁺ T cells, and importantly, RNA-mediated interference of Murr1 in primary resting CD4⁺ lymphocytes increased HIV-1 replication.

Conclusions:  Through its effects on the proteasome, Murr1 acts as a genetic restriction factor that inhibits HIV-1 replication in resting lymphocytes, which could contribute to the regulation of asymptomatic HIV infection and the progression of AIDS.

Keywords: Murr1