Effects of translation initiation factor eIF-5A on the functioning of human T-cell leukemia virus type I Rex and human immunodeficiency virus Rev inhibited trans dominantly by a Rex mutant deficient in RNA binding.

Abstract

The viral transactivator proteins Rex and Rev are necessary for the expression of structural proteins of human T-cell leukemia virus type I and human immunodeficiency virus type 1, respectively. Although the interaction of Rex/Rev with a cellular cofactor(s) has been thought to be required for Rex/Rev action, there is no suitable system to search for the cofactor(s) in mammalian cells. We found that a Rex mutant, TAgRex, which contains a simian virus 40 nuclear localization signal in place of the N-terminal 19 amino acids of Rex, could dominantly inhibit wild-type Rex/Rev functions. The inhibition did not require either Rev response element/Rex response element binding or the oligomerization ability of the mutant, but it did require a region around amino acid 90 of the Rex protein, suggesting that TAgRex sequestered the cellular cofactor. Complementation with the eukaryotic translation initiation factor 5A (eIF-5A) in this system could restore the impaired Rex function. These results indicate that eIF-5A is the cofactor indispensable for Rex function. Additionally, by using a two-hybrid system, the homo-oligomer formation of Rex was found to be mediated by the region around amino acid 90 in addition to Tyr-64 and Trp-65 of Rex protein. Thus, eIF-5A may play a part in the formation of the Rex homo-oligomer.

• Authors: J Katahira, T Ishizaki, H Sakai, A Adachi, K Yamamoto, H Shida
• Journal: Journal of virology (J Virol) Vol. 69 Issue 5 Pg. 3125-33 (May 1995) ISSN: 0022-538X [Print] United States
• PMID: 7707541 (Publication Type: Journal Article)

Chemical References

• DNA Primers
• DNA, Viral
• Gene Products, rev
• Gene Products, rex
• Peptide Initiation Factors
• RNA, Viral
• RNA-Binding Proteins
• eukaryotic translation initiation factor 5A
• rev Gene Products, Human Immunodeficiency Virus

Topics

• Animals
• Base Sequence
• Cell Line
• DNA Primers (genetics)
• DNA, Viral (genetics)
• Gene Products, rev (genetics, metabolism)
• Gene Products, rex (genetics, metabolism)
• Genes, Dominant
• HIV-1 (genetics, metabolism)
• Human T-lymphotropic virus 1 (genetics, metabolism)
• Humans
• Molecular Sequence Data
• Mutation
• Peptide Initiation Factors (metabolism)
• RNA, Viral (metabolism)
• RNA-Binding Proteins
• rev Gene Products, Human Immunodeficiency Virus