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Targeting RNA-protein interactions within the human immunodeficiency virus type 1 lifecycle.


ABSTRACT: RNA-protein interactions are vital throughout the HIV-1 life cycle for the successful production of infectious virus particles. One such essential RNA-protein interaction occurs between the full-length genomic viral RNA and the major structural protein of the virus. The initial interaction is between the Gag polyprotein and the viral RNA packaging signal (psi or ?), a highly conserved RNA structural element within the 5'-UTR of the HIV-1 genome, which has gained attention as a potential therapeutic target. Here, we report the application of a target-based assay to identify small molecules, which modulate the interaction between Gag and ?. We then demonstrate that one such molecule exhibits potent inhibitory activity in a viral replication assay. The mode of binding of the lead molecules to the RNA target was characterized by ¹H NMR spectroscopy.

SUBMITTER: Bell NM 

PROVIDER: S-EPMC3928988 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Targeting RNA-protein interactions within the human immunodeficiency virus type 1 lifecycle.

Bell Neil M NM   L'Hernault Anne A   Murat Pierre P   Richards James E JE   Lever Andrew M L AM   Balasubramanian Shankar S  

Biochemistry 20131210 51


RNA-protein interactions are vital throughout the HIV-1 life cycle for the successful production of infectious virus particles. One such essential RNA-protein interaction occurs between the full-length genomic viral RNA and the major structural protein of the virus. The initial interaction is between the Gag polyprotein and the viral RNA packaging signal (psi or Ψ), a highly conserved RNA structural element within the 5'-UTR of the HIV-1 genome, which has gained attention as a potential therapeu  ...[more]

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