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Role of cell-type-specific endoplasmic reticulum-associated degradation in polyomavirus trafficking

Shauna M Bennett1, Mengxi Jiang, Michael J Imperiale

  • 1Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, Michigan, USA.

Journal of Virology
|June 7, 2013
PubMed

Insights

The endoplasmic reticulum-associated degradation (ERAD) pathway is crucial for BK polyomavirus (BKPyV) entry into host cells. Inhibiting ERAD disrupts viral trafficking and productive infection, impacting BKPyV pathogenesis.

Area of Science:

  • Virology
  • Cell Biology
  • Infectious Diseases

Background:

  • BK polyomavirus (BKPyV) causes persistent infections and severe disease in immunocompromised individuals.
  • BKPyV requires endoplasmic reticulum (ER) transit for productive infection, but its exit mechanism remains unclear.
  • Understanding viral trafficking through the ER is key to developing antiviral strategies.

Purpose of the Study:

  • To investigate the role of the ER-associated degradation (ERAD) pathway in BKPyV intracellular trafficking.
  • To determine if ERAD is essential for BKPyV productive entry into renal proximal tubule epithelial (RPTE) cells.
  • To compare ERAD dependence for viral entry between different polyomaviruses and cell types.

Main Methods:

  • Utilized proteasome and ERAD inhibitors to study BKPyV trafficking.
  • Employed fluorescence in situ hybridization and indirect immunofluorescence to detect viral intermediates.
  • Compared BKPyV entry with simian virus 40 (SV40) in RPTE and CV-1 cells.

Main Results:

  • ERAD is required for productive BKPyV entry into RPTE cells.
  • Inhibiting ERAD led to altered viral trafficking and accumulation of uncoated viral intermediates within the ER.
  • BKPyV accumulated in a specific ER subcompartment (calnexin-rich) upon proteasome inhibition.
  • ERAD inhibition did not impede cytosolic entry of the BKPyV capsid protein VP1.
  • ERAD dependence for cytosolic entry varied between BKPyV and SV40, and between RPTE and CV-1 cells.

Conclusions:

  • The ERAD pathway plays a critical role in BKPyV productive entry and intracellular trafficking.
  • BKPyV utilizes ERAD for efficient exit from the ER, a step essential for infection.
  • The dependence on ERAD for viral entry is virus- and cell-type specific, highlighting complex host-pathogen interactions.

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