Death and gastrointestinal bleeding complicate encephalomyelitis in mice with delayed appearance of CNS IgM after intranasal alphavirus infection

Victoria K. Baxter, Elizabeth M. Troisi, Nathan M. Pate, Julia N. Zhao, Diane E. Griffin

Research output: Contribution to journalArticlepeer-review

Abstract

Central nervous system (CNS) infection of C57BL/6 mice with the TE strain of Sindbis virus (SINV) provides a valuable animal model for studying the pathogenesis of alphavirus encephalomyelitis. While SINV TE inoculated intracranially causes little mortality, 20–30% of mice inoculated intranasally (IN) died 8 to 11 days after infection, the period during which immune cells typically infiltrate the brain and clear infectious virus. To examine the mechanism behind the mortality, mice infected IN with SINV TE were monitored for evidence of neurological disease, and those with signs of severe disease (moribund) were sacrificed and tissues collected. Mice showing the usual mild signs of encephalomyelitis were concurrently sacrificed to serve as time-matched controls (sick). Sixty-eight per cent of the moribund mice, but none of the sick mice, showed upper gastrointestinal bleeding due to gastric ulceration. Clinical disease and gastrointestinal pathology could not be attributed to direct viral infection of tissues outside of the CNS, and brain pathology and inflammation were comparable in sick and moribund mice. However, more SINV antigen was present in the brains of moribund mice, and clearance of infectious virus from the CNS was delayed compared to sick mice. Lower levels of SINV-specific IgM and fewer B220+ B cells were present in the brains of moribund mice compared to sick mice, despite similar levels of antiviral IgM and IgG in serum. These findings highlight the importance of the local antibody response in determining the outcome of viral encephalomyelitis and offer a model system for understanding individual variation in this response.

Original languageEnglish (US)
Article number001005
Pages (from-to)309-320
Number of pages12
JournalJournal of General Virology
Volume99
Issue number3
DOIs
StatePublished - Mar 2018

Keywords

  • Alphavirus encephalomyelitis
  • Central nervous system
  • Gastrointestinal bleeding
  • IgM
  • Sindbis virus
  • Virus clearance

ASJC Scopus subject areas

  • Virology

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