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Viral replication centers and the DNA damage response in JC virus-infected cells

Kimberly D Erickson1, Robert L Garcea2

  • 1The BioFrontiers Institute, University of Colorado, Boulder, CO 80309, United States.

Virology
|February 28, 2019
PubMed

Insights

John Cunningham virus (JCV) uses host DNA damage response (DDR) proteins for replication. This study reveals JCV shares replication strategies with other polyomaviruses (PyVs), impacting understanding of persistent infections and therapies.

Area of Science:

  • Virology
  • Molecular Biology
  • Cellular Biology

Background:

  • John Cunningham virus (JCV), a human polyomavirus (PyV), causes persistent infections.
  • Immunomodulatory therapies can trigger JCV reactivation, leading to progressive multifocal leukoencephalopathy (PML).
  • Viruses, including PyVs, often manipulate the host DNA damage response (DDR) for replication.

Purpose of the Study:

  • To identify host DDR proteins recruited by JCV to viral DNA replication sites.
  • To compare JCV's replication strategy with other PyVs.

Main Methods:

  • In vitro infection of three susceptible cell types.
  • Confocal microscopy to visualize host protein recruitment.
  • Electron tomography of JCV replication centers ('virus factories').

Main Results:

  • JCV recruits a similar set of host DDR proteins to viral DNA replication sites as observed for other PyVs.
  • Electron tomography revealed structural similarities between JCV 'virus factories' and those of murine PyV.
  • Confirmed and extended previous PyV observations to JCV.

Conclusions:

  • JCV employs a replication strategy conserved among polyomaviruses.
  • Understanding JCV's interaction with the host DDR is crucial for managing JCV-associated diseases like PML.
Keywords:
DNA damage responseElectron microscopyJCVPolyomavirusVirus replication

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