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Science 29 March 1996:
Vol. 271. no. 5257, pp. 1858 - 1860
DOI: 10.1126/science.271.5257.1858
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Reports

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

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

Eukaryotic initiation factor 5A (eIF-5A) is a cellular cofactor required 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 eIF-5AM14 proteins blocked Rev trans-activation and Rev-mediated nuclear export.

D. Bevec, H. Jaksche, M. Himmelspach, A. Pacher, M. Schebesta, K. Koettnitz, M. Dobrovnik, R. Csonga, J. Hauber, Sandoz Research Institute, Department of Immunodermatology, A-1235 Vienna, Austria.
M. Oft, Research Institute of Molecular Pathology, A-1030 Vienna, Austria.
T. Wöhl and F. Lottspeich, Max-Planck-Institut für Biochemie, D-82152 Martinsried, Germany.
* To whom correspondence should be addressed.


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