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

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180 Scopus citations

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)-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
JournalNature
Volume426
Issue number6968
DOIs
StatePublished - Dec 18 2003

ASJC Scopus subject areas

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    Ganesh, L., Burstein, E., Guha-Niyogi, A., Louder, M. K., Mascola, J. R., Klomp, L. W. J., Wijmenga, C., Duckett, C. S., & Nabel, G. J. (2003). The gene product Murr1 restricts HIV-1 replication in resting CD4 + lymphocytes. Nature, 426(6968), 853-857. https://doi.org/10.1038/nature02171