Details

Autor(en) / Beteiligte

• Kessl, Jacques J.
• Kutluay, Sebla B.
• Townsend, Dana
• Rebensburg, Stephanie
• Slaughter, Alison
• Larue, Ross C.
• Shkriabai, Nikoloz
• Bakouche, Nordine
• Fuchs, James R.
• Bieniasz, Paul D.
• Kvaratskhelia, Mamuka

Titel

HIV-1 Integrase Binds the Viral RNA Genome and Is Essential during Virion Morphogenesis

Ist Teil von

• Cell, 2016-08, Vol.166 (5), p.1257-1268.e12

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Electronic Journals Library - Freely accessible e-journals

Beschreibungen/Notizen

• While an essential role of HIV-1 integrase (IN) for integration of viral cDNA into human chromosome is established, studies with IN mutants and allosteric IN inhibitors (ALLINIs) have suggested that IN can also influence viral particle maturation. However, it has remained enigmatic as to how IN contributes to virion morphogenesis. Here, we demonstrate that IN directly binds the viral RNA genome in virions. These interactions have specificity, as IN exhibits distinct preference for select viral RNA structural elements. We show that IN substitutions that selectively impair its binding to viral RNA result in eccentric, non-infectious virions without affecting nucleocapsid-RNA interactions. Likewise, ALLINIs impair IN binding to viral RNA in virions of wild-type, but not escape mutant, virus. These results reveal an unexpected biological role of IN binding to the viral RNA genome during virion morphogenesis and elucidate the mode of action of ALLINIs. [Display omitted] •HIV-1 integrase binds viral RNA in virions•Integrase exhibits distinct preference for select RNA structural elements•RNA binding defective mutants of integrase yield non-infectious virions•Allosteric integrase inhibitors impair integrase binding to viral RNA in virions HIV-1 integrase binding to the viral RNA genome is necessary for formation of infectious viral particles and can be impaired by allosteric integrase inhibitors.