Inhibition of protein synthesis by the human immunodeficiency virus type 1 nef gene product.
During productive infection of human T lymphocytes in cell culture, the expression of human immunodeficiency virus type 1 is temporally regulated by virus-encoded regulatory proteins. Among these Nef, whose function has not been clearly elucidated, is thought to alter CD4+ T cells. We examined the possibility that the nef gene interferes with the translation process in a cell-free system. The results demonstrate that the nef gene product mediates an inhibitory effect on protein synthesis. Conversely, the use of antisense nef mRNA did not affect translation. Further observations suggest that this inhibitory effect is an inherent property of the nef gene product itself and not of its mRNA. The data show that the translational repression directed by Nef is a general phenomenon, acting on its own and on other messengers used as reporter mRNAs. We propose that, as a consequence, Nef can play an important role in the pathogenesis of AIDS.
Centre de Recherche du CHUL, Université Laval, Québec, Canada.
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L
Poulin
M
M
Fauchon
A
A
Darveau
J A
JA
Levy
D001483:Base Sequence; D002474:Cell-Free System; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D015693:Gene Products, nef / Q000378:metabolism*; D015754:Genes, nef; D005914:Globins / Q000096:biosynthesis; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008156:Luciferases / Q000096:biosynthesis; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D014176:Protein Biosynthesis / Q000187:drug effects; D011500:Protein Synthesis Inhibitors; D016372:RNA, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D015183:Restriction Mapping; D013601:T-Lymphocytes / Q000378:metabolism* / Q000821:virology; D014158:Transcription, Genetic; D014162:Transfection; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D009838:Oligodeoxyribonucleotides; D011500:Protein Synthesis Inhibitors; D016372:RNA, Antisense; D012333:RNA, Messenger; D054311:nef Gene Products, Human Immunodeficiency Virus; D005914:Globins; D008156:Luciferases; D015500:Chloramphenicol O-Acetyltransferase