Characteristics of viruses derived from nude mice with persistent measles virus infection

Yusaku Abe1, Koichi Hashimoto, Masahiro Watanabe

  • 1Department of Pediatrics, Fukushima Medical University, Fukusjima, Japan. yusakua@fmu.ac.jp

Journal of Virology
|January 25, 2013
PubMed

Insights

Measles virus (MV) in a nude mouse model developed characteristics similar to subacute sclerosing panencephalitis (SSPE) virus. This persistent infection model shows promise for understanding SSPE pathogenesis and developing new treatments.

Area of Science:

  • Virology
  • Neuroscience
  • Immunology

Background:

  • Subacute sclerosing panencephalitis (SSPE) is a severe neurological complication of measles virus (MV) infection.
  • Existing animal models do not fully replicate the unique virological characteristics of SSPE-associated MV isolates.
  • Understanding the mechanisms driving SSPE pathogenesis is crucial for therapeutic development.

Purpose of the Study:

  • To establish and characterize a novel animal model for persistent measles virus infection that mimics SSPE virus properties.
  • To investigate the virological and pathological changes in the brain following subarachnoid inoculation of MV in nude mice.
  • To evaluate the potential of this model for studying SSPE and testing therapeutic strategies.

Main Methods:

  • Nude mice were inoculated with the Edmonston strain of measles virus into the subarachnoid space.
  • Viral load, brain infection, and survival rates were monitored.
  • Gene sequencing was performed on recovered viruses to identify mutations.
  • The neurovirulence of brain-derived virus was assessed through subsequent challenge studies.

Main Results:

  • Inoculated nude mice exhibited significant weight loss and reduced survival (mean 73.2 days).
  • Brain viral loads increased substantially (4- to 400-fold), with confirmed infection via immunostaining.
  • Gene sequencing revealed frequent mutations in matrix proteins, notably uridine-to-cytosine transitions.
  • The brain-derived virus showed reduced ability to form free virus particles and was significantly more virulent upon re-challenge (shorter survival, 34.7 days).

Conclusions:

  • The MV Edmonston strain, after persistent infection in nude mice, acquired characteristics resembling SSPE virus.
  • This nude mouse model demonstrates key features of SSPE, including neuroinvasion, altered viral properties, and increased virulence.
  • This model offers a valuable platform for future research into SSPE pathogenesis and the evaluation of potential antiviral therapies.

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