FUNCTIONAL ANALOGIES WITH CELLULAR ONCOGENE PRODUCTS IMPLY A ROLE FOR HIV-F (3'ORF) IN CELL REGULATION

Important note: Information in this article was accurate in 1989. The state of the art may have changed since the publication date.

FUNCTIONAL ANALOGIES WITH CELLULAR ONCOGENE PRODUCTS IMPLY A ROLE FOR HIV-F (3'ORF) IN CELL REGULATION

Vaccines 88. New Chemical and Genetic Approaches to Vaccination: Prevention of AIDS and Other Viral, Bacterial, and Parasitic Diseases. Ginsberg H et al, eds. New York, Cold Spring Harbor Laboratory, p. 311-6, 1988.. Unique Identifier : AIDSLINE ICDB/89649774
Guy B; Kieny MP; Lecocq JP; Riviere Y; Montagnier L; Girard M; Transgene, 67082 Strasbourg Cedex, France

Abstract: The genome of HIV, in addition to gag, pol, and env, codes at least five other proteins. The F (3'orf, orfB) gene encodes a 206-amino acid protein myristilated on its amino-terminal glycine. Biochemical properties of the mammalian and Escherichia coli recombinant F proteins were examined, and results are presented here indicating a role for F in cell regulation. It is demonstrated that the HIV-F gene product exhibits functional analogies to the products of two cellular oncogenes. F, like pp60(src), bears a covalently attached myristic acid residue at its amino terminus and is phosphorylated, by protein kinase C, at a serine/threonine residue close to the acylation site. Second, F resembles the ras-gene product in its GTP-binding, GTPase, and autophosphorylation activities. F may intervene in host cell regulation. Down-regulation of the lymphocyte T4 antigen is an important event in the pathophysiology of AIDS. To explore whether F might contribute to T4 down-regulation, HIV-F was expressed in T4+ lymphocytes, using a recombinant vaccinia virus. Infection by VVfHIV resulted in marked depression of T4. The dual observations of analogies with cellular oncogene products and F-mediated down-regulation of an important host protein product predict that F acts, with tat and art, to regulate the HIV-infected cell. (27 Refs)

Keywords: Amino Acid Sequence Cell Line CD4-Positive T-Lymphocytes/IMMUNOLOGY Flow Cytometry G-Proteins/GENETICS *Gene Expression Regulation Human HIV/*GENETICS Muscle Proteins/*GENETICS *Proto-Oncogenes Retroviridae Proteins/*GENETICS MEETING PAPER

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