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

Lakshmanan Ganesh, Ezra Burstein, Anuradha Guha-Niyogi, Mark K. Louder, John R. Mascola, Leo W J Klomp, Cisca Wijmenga, Colin S. Duckett, Gary J. Nabel

Research output: Contribution to journalArticlepeer-review

186 Scopus citations


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)-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.

Original languageEnglish (US)
Pages (from-to)853-857
Number of pages5
Issue number6968
StatePublished - Dec 18 2003
Externally publishedYes

ASJC Scopus subject areas

  • General


Dive into the research topics of 'The gene product Murr1 restricts HIV-1 replication in resting CD4 + lymphocytes'. Together they form a unique fingerprint.

Cite this