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Inhibition of Protein Synthesis by the Human Immunodeficiency Virus Type 1 nef Gene Product

¹ Infectiologie, Centre de Recherche du CHUL and Département de microbiologie, Médecine, Université Laval, Québec, Canada G1V 4G2
² Département de Biochimie, Université Laval, Québec, Canada G1K 7P4
and³ Cancer Research Institute and Department of Medicine, University of California, School of Medicine, San Francisco, California 94143, U.S.A.

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.

Received 21 March 1994; accepted 29 June 1994.

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