Inhibition of endocytic pathways impacts cytomegalovirus maturation

Madeline A Archer1, Teal M Brechtel1, Leslie E Davis1

  • 1Department of Microbiology and Immunology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.

Scientific Reports
|April 14, 2017
PubMed

Insights

Endocytic pathways are crucial for human cytomegalovirus (HCMV) maturation and release, even though HCMV enters cells via fusion. Inhibiting endocytosis reduced HCMV yield and compromised viral assembly.

Area of Science:

  • Virology
  • Cell Biology
  • Molecular Biology

Background:

  • Endocytosis plays a key role in viral entry into host cells.
  • The role of endocytosis in viral trafficking post-entry is not fully understood.
  • Human cytomegalovirus (HCMV) primarily enters fibroblasts via cell membrane fusion.

Purpose of the Study:

  • To investigate the post-entry role of endocytosis in the HCMV life cycle.
  • To determine if endocytic pathways influence HCMV maturation and egress.

Main Methods:

  • Utilized laboratory strains AD169 and Towne of HCMV.
  • Employed pharmacological inhibitors of dynamin-2 and clathrin terminal domain (TD) ligand association.
  • Analyzed viral protein expression, growth rates, virus yields, and viral assembly compartment (vAC) formation.
  • Conducted transmission electron microscopy (TEM) on infected cells.

Main Results:

  • HCMV entry was not inhibited by endocytosis inhibitors.
  • Inhibitors significantly reduced HCMV growth rates and final virus yields.
  • Clathrin accumulated in the vAC, co-localizing with pp150, and vAC formation was compromised.
  • Nuclear nucleocapsid assembly remained intact, but cytoplasmic virus maturation was severely impaired.

Conclusions:

  • Endocytic pathways are implicated in HCMV maturation and egress.
  • Endocytosis is essential for efficient HCMV replication beyond the entry stage.
  • Targeting endocytic pathways could be a strategy to control HCMV infection.

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