Age-dependent pathogenesis of murine gammaherpesvirus 68 infection of the central nervous system

Hye Jeong Cho, Sungbum Kim, Sung Eun Kwak, Tae Cheon Kang, Hee Sung Kim, Hyung Joo Kwon, Yoon Won Kim, Yong Sun Kim, Eun Kyung Choi, Moon Jung Song

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Gammaherpesvirus infection of the central nervous system (CNS) has been linked to various neurological diseases, including meningitis, encephalitis, and multiple sclerosis. However, little is known about the interactions between the virus and the CNS in vitro or in vivo. Murine gammaherpesvirus 68 (MHV-68 or γHV-68) is genetically related and biologically similar to human gammaherpesviruses, thereby providing a tractable animal model system in which to study both viral pathogenesis and replication. In the present study, we show the successful infection of cultured neuronal cells, microglia, and astrocytes with MHV-68 to various extents. Upon intracerebroventricular injection of a recombinant virus (MHV-68/LacZ) into 4-5-week-old and 9-10-week-old mice, the 4-5-week-old mice displayed high mortality within 5-7 days, while the majority of the 9-10-week-old mice survived until the end of the experimental period. Until a peak at 3-4 days post-infection, viral DNA replication and gene expression were similar in the brains of both mouse groups, but only the 9-10-week-old mice were able to subdue viral DNA replication and gene expression after 5 days post-infection. Pro-inflammatory cytokine mRNAs of tumor necrosis factor-α, interleukin 1β, and interleukin 6 were highly induced in the brains of the 4-5-week-old mice, suggesting their possible contributions as neurotoxic factors in the agedependent control of MHV-68 replication of the CNS.

Original languageEnglish
Pages (from-to)105-111
Number of pages7
JournalMolecules and cells
Volume27
Issue number1
DOIs
Publication statusPublished - 2009 Jan

Keywords

  • Age-dependency
  • Gammaherpesvirus
  • Multiple sclerosis
  • Neurological diseases
  • Proinflammatory cytokines

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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