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Inhibition of HIV-1 Replication in Lymphocytes by Mutants of the Rev Cofactor eIF-5A

1996; American Association for the Advancement of Science; Volume: 271; Issue: 5257 Linguagem: Inglês

10.1126/science.271.5257.1858

1095-9203

Dorian Bevec, Herbert Jaksche, Martin Oft, Thorsten Wöhl, Michèle Himmelspach, Alexandra Pacher, Michael Schebesta, Karl Koettnitz, Marika Dobrovnik, Robert Csonga, Friedrich Lottspeich, Joachim Hauber,

Bacteriophages and microbial interactions

Eukaryotic initiation factor 5A(eIF-5A) is a cellular cofactor require d for the function of the human immunodeficiency virus type-1 (HIV-1) Rev trans-activator protein. The majority of a set of eIF-5A mutants did not support growth of yeast cells having an inactivated genomic copy of eIF-5A, indicating that the introduced mutation eliminated eIF-5A activity. Two nonfunctional mutants, eIF-5AM13 and eIF-5AM14, retained their binding capacity for the HIV-1 Rev response element:Rev complex. Both mutants were constitutively expressed in human T cells. When these T cells were infected with replication-competent HIV-1, virus replication was inhibited. The eIF-5AM13 and eIF5AM14 proteins blocked Rev trans-activation and Rev-mediated nuclear export.