Inhibition of HIV-1 replication by eIF3f.
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.
Valente
Susana T
ST
Department 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, USA. sv2033@columbia.edu
Gilmartin
Greg M
GM
Mott
Christina
C
Falkard
Brie
B
Goff
Stephen P
SP
D039621:Eukaryotic Initiation Factor-3 / Q000276:immunology / Q000502:physiology*; D015723:Gene Library; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology; D011485:Protein Binding; D012367:RNA, Viral / Q000032:analysis / Q000187:drug effects; D020079:Terminal Repeat Sequences / Q000187:drug effects; D014161:Transduction, Genetic; D014779:Virus Replication / Q000276:immunology*
D039621:Eukaryotic Initiation Factor-3; D010446:Peptide Fragments; D012367:RNA, Viral; C096013:EIF3I protein, human