Journal of NeuroVirology

, Volume 11, Issue 6, pp 512–524

Differential responses of human brain cells to West Nile virus infection

  • Maxim C. -J. Cheeran
  • Shuxian Hu
  • Wen S. Sheng
  • Ayesha Rashid
  • Phillip K. Peterson
  • James R. Lokensgard
Article

Abstract

In recent years, West Nile virus (WNV) has emerged as a major cause of encephalitis in the United States. However, the neuropathogenesis of this flavivirus is poorly understood. In the present study, the authors used primary human brain cell cultures to investigate two neuropathogenic features: viral replication and induction of cytokines. Although neurons and astrocytes were found to support productive WNV infection, viral growth was poorly permissive in microglial cells. Compared to neuronal cultures that sustained viral growth for at least 2 weeks, replication peaked in astrocytes by 72 h post infection. In response to viral infection, astrocytes produced chemokines (CXCL10 and CCL5), but none of the cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-6, interferon α or γ) tested could be detected. Although microglial cells failed to support viral replication, WNV induced production of the proinflammatory cytokines IL-6 and TNF-α. Microglial cells also released robust amounts of the chemokines CXCL10 and CCL2, as well as lower levels of CCL5, in response to WNV infection. WNV-induced chemokine and cytokine production by microglia was coupled with activation of mitogen-activated protein kinase (MAPK) intracellular signaling pathways. Inhibition of p38 MAPK decreased chemokine production in response to WNV. Taken together, these findings suggest that microglial cell responses may influence the neuropathogenesis of WNV infection.

Keywords

chemokines cytokines glia West Nile virus 

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Copyright information

© Journal of NeuroVirology, Inc. 2005

Authors and Affiliations

  • Maxim C. -J. Cheeran
    • 1
    • 2
    • 3
  • Shuxian Hu
    • 1
    • 2
  • Wen S. Sheng
    • 1
    • 2
  • Ayesha Rashid
    • 2
  • Phillip K. Peterson
    • 1
    • 2
  • James R. Lokensgard
    • 1
    • 2
  1. 1.Neuroimmunology Laboratory, Minneapolis Medical Research FoundationUniversity of Minnesota Medical SchoolMinneapolisUSA
  2. 2.Center for Infectious Disease and Microbiology Translational Research, Department of MedicineUniversity of Minnesota Medical SchoolUSA
  3. 3.Neuroimmunology Laboratory, Center for Infectious Disease and Microbiology Translational ResearchUniversity of Minnesota, 3-222 MTRF/LRBMinneapolisUSA

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