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, USA
  • Max Essex, Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, USA
  • Jørgen Kjems
  • Tun-Hou Lee, Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, USA
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.
OriginalsprogEngelsk
TidsskriftAIDS Research and Human Retroviruses
Vol/bind22
Nummer1
Sider (fra-til)76-82
Antal sider7
ISSN0889-2229
DOI
StatusUdgivet - 26 jan. 2006

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