Adenovirus entry: Stability, uncoating, and nuclear import

Mol Microbiol. 2022 Oct;118(4):309-320. doi: 10.1111/mmi.14909. Epub 2022 Apr 26.

Abstract

Adenoviruses (AdVs) are widespread in vertebrates. They infect the respiratory and gastrointestinal tracts, the eyes, heart, liver, and kidney, and are lethal to immunosuppressed people. Mastadenoviruses infecting mammals comprise several hundred different types, and many specifically infect humans. Human adenoviruses are the most widely used vectors in clinical applications, including cancer treatment and COVID-19 vaccination. AdV vectors are physically and genetically stable and generally safe in humans. The particles have an icosahedral coat and a nucleoprotein core with a DNA genome. We describe the concept of AdV cell entry and highlight recent advances in cytoplasmic transport, uncoating, and nuclear import of the viral DNA. We highlight a recently discovered "linchpin" function of the virion protein V ensuring cytoplasmic particle stability, which is relaxed at the nuclear pore complex by cues from the E3 ubiquitin ligase Mind bomb 1 (MIB1) and the proteasome triggering disruption. Capsid disruption by kinesin motor proteins and microtubules exposes the linchpin and renders protein V a target for MIB1 ubiquitination, which dissociates V from viral DNA and enhances DNA nuclear import. These advances uncover mechanisms controlling capsid stability and premature uncoating and provide insight into nuclear transport of nucleic acids.

Keywords: DNA nuclear transport; Mind bomb 1 (MIB1) E3 ubiquitin ligase; nuclear pore complex (NPC); ubiquitin proteasome system; virus entry and disassembly.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Adenoviridae* / genetics
  • Adenoviridae* / metabolism
  • Animals
  • COVID-19 Vaccines
  • COVID-19*
  • Capsid Proteins / genetics
  • DNA, Viral / genetics
  • DNA, Viral / metabolism
  • Humans
  • Kinesins
  • Mammals / genetics
  • Mammals / metabolism
  • Nuclear Pore / genetics
  • Nuclear Pore / metabolism
  • Nucleoproteins / metabolism
  • Proteasome Endopeptidase Complex / metabolism
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • DNA, Viral
  • Proteasome Endopeptidase Complex
  • Kinesins
  • COVID-19 Vaccines
  • Capsid Proteins
  • Ubiquitin-Protein Ligases
  • Nucleoproteins