DBR1 siRNA inhibition of HIV-1 replication.

Abstract:

BACKGROUND:HIV-1 and all retroviruses are related to retroelements of simpler organisms such as the yeast Ty elements. Recent work has suggested that the yeast retroelement Ty1 replicates via an unexpected RNA lariat intermediate in cDNA synthesis. The putative genomic RNA lariat intermediate is formed by a 2'-5' phosphodiester bond, like that found in pre-mRNA intron lariats and it facilitates the minus-strand template switch during cDNA synthesis. We hypothesized that HIV-1 might also form a genomic RNA lariat and therefore that siRNA-mediated inhibition of expression of the human RNA lariat de-branching enzyme (DBR1) expression would specifically inhibit HIV-1 replication. RESULTS:We designed three short interfering RNA (siRNA) molecules targeting DBR1, which were capable of reducing DBR1 mRNA expression by 80% and did not significantly affect cell viability. We assessed HIV-1 replication in the presence of DBR1 siRNA and found that DBR1 knockdown led to decreases in viral cDNA and protein production. These effects could be reversed by cotransfection of a DBR1 cDNA indicating that the inhibition of HIV-1 replication was a specific effect of DBR1 underexpression. CONCLUSION:These data suggest that DBR1 function may be needed to debranch a putative HIV-1 genomic RNA lariat prior to completion of reverse transcription.

journal_name

Retrovirology

journal_title

Retrovirology

authors

Ye Y,De Leon J,Yokoyama N,Naidu Y,Camerini D

doi

10.1186/1742-4690-2-63

subject

Has Abstract

pub_date

2005-10-18 00:00:00

pages

63

issn

1742-4690

pii

1742-4690-2-63

journal_volume

2

pub_type

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