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

Cell. 2016 Aug 25;166(5):1257-1268.e12. doi: 10.1016/j.cell.2016.07.044.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Genome, Viral*
  • HEK293 Cells
  • HIV Integrase / genetics
  • HIV Integrase / metabolism*
  • HIV Integrase Inhibitors / pharmacology
  • HIV-1 / drug effects
  • HIV-1 / enzymology
  • HIV-1 / growth & development*
  • Humans
  • Morphogenesis
  • Nucleocapsid / drug effects
  • Protein Binding
  • RNA, Viral / metabolism*
  • Virion / drug effects
  • Virion / enzymology
  • Virion / growth & development*
  • Virus Integration / drug effects


  • HIV Integrase Inhibitors
  • RNA, Viral
  • HIV Integrase
  • p31 integrase protein, Human immunodeficiency virus 1