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

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

Author information

1
Center for Retrovirus Research, Ohio State University, Columbus, OH 43210, USA; College of Pharmacy, Ohio State University, Columbus, OH 43210, USA.
2
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Laboratory of Retrovirology, Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY 10016, USA.
3
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
4
College of Pharmacy, Ohio State University, Columbus, OH 43210, USA.
5
Laboratory of Retrovirology, Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY 10016, USA; Howard Hughes Medical Institute, Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY 10016, USA.
6
Center for Retrovirus Research, Ohio State University, Columbus, OH 43210, USA; College of Pharmacy, Ohio State University, Columbus, OH 43210, USA. Electronic address: kvaratskhelia.1@osu.edu.

Abstract

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.

PMID:
27565348
PMCID:
PMC5003418
DOI:
10.1016/j.cell.2016.07.044
[Indexed for MEDLINE]
Free PMC Article

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