Increased proinflammatory cytokine and chemokine responses and microglial infection following inoculation with neural stem cells infected with polytropic murine retroviruses

Virology. 2006 Oct 10;354(1):143-53. doi: 10.1016/j.virol.2006.06.016. Epub 2006 Jul 27.


Proinflammatory cytokines and chemokines are often detected in brain tissue of patients with neurological diseases such as multiple sclerosis (MS), HIV-associated dementia (HAD) and Alzheimer's disease (AD). We have utilized a mouse model of retrovirus-induced neurological disease to examine how these proinflammatory responses contribute to neuropathogenesis. In previous studies with this model, a correlation was found between neurovirulence and cytokine and chemokine expression. However, it was unclear whether the induction of these cytokines and chemokines was in response to specific virus envelope determinants or was regulated by the level of virus infection in the brain. In the current study, we demonstrated that multiple polytropic retroviruses induced cytokine and chemokine mRNA expression following increased virus levels in the brain. Increased virus levels of polytropic viruses also correlated with increased neuropathogenesis. In contrast, the ecotropic retrovirus, FB29, did not induce cytokine or chemokine mRNA expression or neurological disease, despite virus levels either similar to or higher than the polytropic retroviruses. As polytropic and ecotropic viruses utilize different receptors for entry, these receptors may play a critical role in the induction of these innate immune responses in the brain.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Astrocytes / immunology
  • Brain / immunology
  • Brain / virology
  • Central Nervous System Viral Diseases / immunology*
  • Central Nervous System Viral Diseases / pathology
  • Central Nervous System Viral Diseases / physiopathology
  • Central Nervous System Viral Diseases / virology
  • Chemokines / biosynthesis
  • Chemokines / genetics
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Disease Models, Animal
  • Gene Expression
  • Immunohistochemistry
  • Mice
  • Microglia / immunology
  • Microglia / virology*
  • Neurons / cytology
  • Neurons / virology
  • RNA, Messenger / analysis
  • Receptors, Virus / metabolism
  • Retroviridae / immunology*
  • Retroviridae / physiology
  • Retroviridae Infections / immunology*
  • Retroviridae Infections / physiopathology
  • Retroviridae Infections / virology
  • Stem Cell Transplantation
  • Stem Cells / virology*
  • Viral Proteins / analysis


  • Chemokines
  • Cytokines
  • RNA, Messenger
  • Receptors, Virus
  • Viral Proteins