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The Effect of a Single Nucleotide Substi ... HIV Type 1 Envelope Expression


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

7333

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.


Paca-Uccaralertkun S, Damgaard CK, Auewarakul P, Thitithanyanont A, Suphaphiphat P, Essex M, Kjems J, Lee TH

AIDS research and human retroviruses

2006-01-01 00:00

22

1

76-82

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,Gene Products, rev,RNA, Messenger,RNA, Viral

Department of Microbiology, Faculty of Science, Mahidol University, Payatai, Bangkok 10400, Thailand.

AIDS Res. Hum. Retroviruses

FIC D43 TW000004-16

0889-2229

10.1089/aid.2006.22.76


0

False

16438649

Christian Damgaard
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