Lyssavirus infection activates interferon gene expression in the brain.
To investigate the innate immune response within the brain to lyssavirus infection, key transcripts indicative of innate defences were measured in a mouse model system. Following infection with Rabies virus, transcript levels for type 1 interferons (IFN-alpha and -beta), the inflammatory mediator interleukin 6 (IL-6) and the antiviral protein Mx1 increased in the brains of mice. Intracranial inoculation resulted in the early detection of virus replication and rapid expression within the brain of the innate immune response genes. Transcripts for type 1 IFNs declined as the disease progressed. Peripheral, extraneural inoculation delayed the host response until virus entered the brain, but then resulted in a large increase in the level of IFN-beta, IL-6 and Mx1 transcripts. Induction of this response was also observed following infection with the related European bat lyssaviruses, a group of zoonotic viruses capable of causing fatal, rabies-like disease in mammalian species.
Johnson
Nicholas
N
Rabies and Wildlife Zoonoses Group (WHO Collaborating Centre for the Characterization of Rabies and Rabies-related Viruses), Department of Virology, Veterinary Laboratories Agency (Weybridge), Addlestone, Surrey KT15 3NB, UK.
McKimmie
Clive S
CS
Virology, Centre for Infectious Diseases, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh EH9 1QH, UK.
Mansfield
Karen L
KL
Rabies and Wildlife Zoonoses Group (WHO Collaborating Centre for the Characterization of Rabies and Rabies-related Viruses), Department of Virology, Veterinary Laboratories Agency (Weybridge), Addlestone, Surrey KT15 3NB, UK.
Wakeley
Philip R
PR
Technology Transfer Unit, Veterinary Laboratories Agency (Weybridge), Addlestone, Surrey KT15 3NB, UK.
Brookes
Sharon M
SM
Rabies and Wildlife Zoonoses Group (WHO Collaborating Centre for the Characterization of Rabies and Rabies-related Viruses), Department of Virology, Veterinary Laboratories Agency (Weybridge), Addlestone, Surrey KT15 3NB, UK.
Fazakerley
John K
JK
Virology, Centre for Infectious Diseases, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh EH9 1QH, UK.
Fooks
Anthony R
AR
Rabies and Wildlife Zoonoses Group (WHO Collaborating Centre for the Characterization of Rabies and Rabies-related Viruses), Department of Virology, Veterinary Laboratories Agency (Weybridge), Addlestone, Surrey KT15 3NB, UK.
D000818:Animals; D001921:Brain / Q000276:immunology*; D002685:Chiroptera / Q000821:virology; D019204:GTP-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D016898:Interferon-alpha / Q000235:genetics*; D016899:Interferon-beta / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics; D018114:Lyssavirus / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D051379:Mice; D064547:Myxovirus Resistance Proteins; D012313:RNA / Q000235:genetics / Q000378:metabolism; D011818:Rabies / Q000235:genetics / Q000276:immunology / Q000821:virology; D011820:Rabies virus / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology; D018353:Rhabdoviridae Infections / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D014779:Virus Replication
D016898:Interferon-alpha; D015850:Interleukin-6; C579070:Mx1 protein, mouse; D064547:Myxovirus Resistance Proteins; D012313:RNA; D016899:Interferon-beta; D019204:GTP-Binding Proteins