HIV-1 viral cores enter the nucleus collectively through the nuclear endocytosis-like pathway

Sci China Life Sci. 2021 Jan;64(1):66-76. doi: 10.1007/s11427-020-1716-x. Epub 2020 May 14.

Abstract

It is recognized that HIV-1 capsid cores are disassembled in the cytoplasm, releasing their genomes into the nucleus through nuclear pores, but there is also evidence showing the capsid (CA) exists in the nucleus. Whether HIV-1 enters the nucleus and how it enters the nucleus through the undersized nuclear pore remains mysterious. Based on multicolor labeling and real-time imaging of the viral and cellular components, our observations via light and electron microscopy suggest that HIV-1 selectively gathered at the microtubule organization center (MTOC), leading the nearby nuclear envelope (NE) to undergo deformation, invagination and restoration to form a nuclear vesicle in which the viral particles were wrapped; then, the inner membrane of the nuclear vesicle ruptured to release HIV-1 into the nucleus. This unexpected discovery expands our understanding of the complexity of HIV-1 nuclear entry, which may provide new insights to HIV-1 virology.

Keywords: HIV-1; nuclear endocytosis-like; nuclear entry.

MeSH terms

  • Active Transport, Cell Nucleus
  • Capsid Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Nucleus / metabolism*
  • Cell Nucleus / ultrastructure
  • Cell Nucleus / virology
  • Endocytosis*
  • HEK293 Cells
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / metabolism*
  • HIV-1 / physiology
  • Humans
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Microtubule-Organizing Center / metabolism
  • Microtubule-Organizing Center / virology
  • Nuclear Envelope / metabolism
  • Nuclear Envelope / ultrastructure
  • Nuclear Envelope / virology
  • Nuclear Pore / metabolism*
  • Nuclear Pore / ultrastructure
  • Nuclear Pore / virology
  • Time-Lapse Imaging / methods
  • Virion / metabolism*
  • Virion / ultrastructure

Substances

  • Capsid Proteins