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INAUGURAL ARTICLE by a Recently Elected Academy Member:Inhibition of HIV-1 replication by eIF3f |
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| Authors: | Susana T. Valente Greg M. Gilmartin Christina Mott Brie Falkard Stephen P. Goff |
| Affiliation: | aDepartment of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, HHSC 1310c, 701 West 168th Street, New York, NY 10032; and ;bDepartment of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, Vermont Cancer Center, University of Vermont, Burlington, VT 05405 |
| Abstract: | Viruses often use host machinery in unusual ways to execute different steps during their replication. To identify host factors critical for virus replication, we screened cDNA expression libraries for genes or gene fragments that could interfere with HIV-1 vector transduction. The DNA clone that most potently inhibited HIV-1 expression encoded the N-terminal 91 aa of the eukaryotic initiation factor 3 subunit f (N91-eIF3f). Overexpression of N91-eIF3f or full-length eIF3f drastically restricted HIV-1 replication by reducing nuclear and cytoplasmic viral mRNA levels. N91-eIF3f and eIF3f specifically targeted the 3′ long terminal repeat (3′LTR) region in the viral mRNA. We show that the 3′ end cleavage of HIV-1 mRNA precursors is specifically reduced in N91-eIF3f expressing cells. Our results suggest a role of eIF3f in mRNA maturation and that it can specifically interfere with the 3′ end processing of HIV-1 mRNAs. |
| Keywords: | cDNA genetic screen HIV-1 restriction RNA maturation translation factor |