Interferon regulatory factor 2 protects mice from lethal viral neuroinvasion. Academic Article uri icon

Overview

abstract

  • The host responds to virus infection by activating type I interferon (IFN) signaling leading to expression of IFN-stimulated genes (ISGs). Dysregulation of the IFN response results in inflammatory diseases and chronic infections. In this study, we demonstrate that IFN regulatory factor 2 (IRF2), an ISG and a negative regulator of IFN signaling, influences alphavirus neuroinvasion and pathogenesis. A Sindbis virus strain that in wild-type (WT) mice only causes disease when injected into the brain leads to lethal encephalitis in Irf2-/- mice after peripheral inoculation. Irf2-/- mice fail to control virus replication and recruit immune infiltrates into the brain. Reduced B cells and virus-specific IgG are observed in the Irf2-/- mouse brains despite the presence of peripheral neutralizing antibodies, suggesting a defect in B cell trafficking to the central nervous system (CNS). B cell-deficient μMT mice are significantly more susceptible to viral infection, yet WT B cells and serum are unable to rescue the Irf2-/- mice. Collectively, our data demonstrate that proper localization of B cells and local production of antibodies in the CNS are required for protection. The work advances our understanding of host mechanisms that affect viral neuroinvasion and their contribution to immunity against CNS infections.

publication date

  • November 29, 2016

Research

keywords

  • Alphavirus Infections
  • B-Lymphocytes
  • Brain Diseases
  • Cell Movement
  • Interferon Regulatory Factor-2
  • Sindbis Virus

Identity

PubMed Central ID

  • PMC5154937

Scopus Document Identifier

  • 85008440106

Digital Object Identifier (DOI)

  • 10.1126/science.1235208

PubMed ID

  • 27899441

Additional Document Info

volume

  • 213

issue

  • 13