Inhibition of HIV-1 replication in lymphocytes by mutants of the Rev cofactor eIF-5A.
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.
Bevec
D
D
Sandoz Research Institute, Department of Immunodermatology, Vienna, Austria.
Jaksche
H
H
Oft
M
M
Wöhl
T
T
Himmelspach
M
M
Pacher
A
A
Schebesta
M
M
Koettnitz
K
K
Dobrovnik
M
M
Csonga
R
R
Lottspeich
F
F
Hauber
J
J
D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D015694:Gene Products, rev / Q000378:metabolism*; D015752:Genes, env; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D015533:Transcriptional Activation; D014779:Virus Replication; D054321:rev Gene Products, Human Immunodeficiency Virus; D000097574:Eukaryotic Translation Initiation Factor 5A
D015694:Gene Products, rev; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D054321:rev Gene Products, Human Immunodeficiency Virus; D000097574:Eukaryotic Translation Initiation Factor 5A