A Heterologous, High-Affinity RNA Ligand for Human Immunodeficiency Virus Gag Protein Has RNA Packaging Activity

AUTOR(ES)

Clever, Jared L.

FONTE

American Society for Microbiology

RESUMO

Retroviral RNA encapsidation depends on the specific binding of Gag proteins to packaging (ψ) signals in genomic RNA. We investigated whether an in vitro-selected, high-affinity RNA ligand for the nucleocapsid (NC) portion of the Gag protein from human immunodeficiency virus type 1 (HIV-1) could mediate packaging into HIV-1 virions. We find that this ligand can functionally substitute for one of the Gag-binding elements (termed SL3) in the HIV-1 ψ locus to support packaging and viral infectivity in cis. By contrast, this ligand, which fails to dimerize spontaneously in vitro, is unable to replace a different ψ element (termed SL1) which is required for both Gag binding and dimerization of the HIV-1 genome. A single point mutation within the ligand that eliminates high-affinity in vitro Gag binding also abolishes its packaging activity at the SL3 position. These results demonstrate that specific binding of Gag or NC protein is a critical determinant of genomic RNA packaging.

Documentos Relacionados

• Identification of a high-affinity RNA-binding site for the human immunodeficiency virus type 1 Rev protein
• Identification of a high-affinity RNA-binding site for the human immunodeficiency virus type 1 Rev protein.
• High-affinity RNA ligands to human alpha-thrombin.
• Only high-affinity receptors for interleukin 2 mediate internalization of ligand.
• Using in vitro selection to direct the covalent attachment of human immunodeficiency virus type 1 Rev protein to high-affinity RNA ligands.