The Effect of a Single Nucleotide Substitution in the Splicing Silencer in the tat/rev Intron on HIV Type 1 Envelope Expression

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  • Saowakon Paca-Uccaralertkun, Department of Microbiology, Faculty of Science, Mahidol University, Payatai, Thailand
  • Christian Kroun Damgaard
  • Prasert Auewarakul, Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
  • Arunee Thitithanyanont, Department of Microbiology, Faculty of Science, Mahidol University, Payatai, Bangkok, Thailand
  • Pirada Suphaphiphat, Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, United States
  • Max Essex, Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, United States
  • Jørgen Kjems
  • Tun-Hou Lee, Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, United States
A complex mRNA splicing pattern, which remains to be fully characterized, influences HIV-1 gene expression. In this study, poor envelope expression of a primary HIV-1 isolate was observed and linked to increased splicing of the two coding exons of tat/rev. The substitution of a nucleotide G, located 28 nucleotides upstream of the splice acceptor site SA7 in the recently identified intron splicing silencer sequence, was found to be responsible for the poor envelope expression. A single nucleotide substitution of G with A at this position results in a poor envelope expression phenotype. Moreover, substitution of the nucleotide G with any other nucleotide in an infectious HIV-1 proviral clone, HXB2RU3, results in poor envelope expression. The substitution of this nucleotide reduces the hnRNP A1 binding affinity but increases the splicing of env mRNA. The nucleotide G at this position is highly conserved among HIV-1 isolates and appears to play a critical role in HIV-1 splicing.
Original languageEnglish
JournalAIDS Research and Human Retroviruses
Volume22
Issue1
Pages (from-to)76-82
Number of pages7
ISSN0889-2229
DOIs
Publication statusPublished - 26 Jan 2006

    Research areas

  • Animals, Base Sequence, COS Cells, Cercopithecus aethiops, Gene Expression, Gene Products, rev, Gene Silencing, Genes, tat, HIV-1, Introns, Point Mutation, Protein Binding, RNA Splicing, RNA, Messenger, RNA, Viral, rev Gene Products, Human Immunodeficiency Virus

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