Pathogenesis of Dugbe virus infection in wild-type and interferon-deficient mice.
In 129 mice, infection with the nairovirus Dugbe virus (DUGV) was lethal following intracerebral but not intraperitoneal inoculation. Following both routes of inoculation, immunostaining of tissue sections demonstrated virus-positive cells in the brain, indicating that DUGV is neuroinvasive in mice. Many brain areas were affected and neurones were the main cell type infected. Infected cells showed punctate accumulations of viral nucleoprotein in the cytoplasm, indicative of virus replication sites. Immunostaining for activated caspase 3 demonstrated no evidence of apoptosis. The type I interferon (IFN) system plays a significant role in defence against DUGV, as 129 IFN-alpha/beta R(-/-) mice died rapidly following both intraperitoneal and intracerebral inoculations. Studies were undertaken to determine whether the IFN-inducible proteins, protein kinase R (PKR) and MxA, were important for protection; neither PKR nor constitutively expressed human MxA played significant roles.
Boyd
Amanda
A
Centre for Infectious Diseases, College of Medicine and Veterinary Medicine, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, UK.
Fazakerley
John K
JK
Centre for Infectious Diseases, College of Medicine and Veterinary Medicine, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, UK.
Bridgen
Anne
A
Department of Biomedical Sciences, University of Ulster, Cromore Road, Coleraine BT52 1SA, Northern Ireland, UK.
D000818:Animals; D001921:Brain / Q000821:virology; D002044:Bunyaviridae Infections / Q000209:etiology* / Q000276:immunology* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007267:Injections; D007274:Injections, Intraperitoneal; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D064547:Myxovirus Resistance Proteins; D016855:Nairovirus / Q000276:immunology / Q000472:pathogenicity*; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000172:deficiency* / Q000235:genetics; D014774:Virulence; D019892:eIF-2 Kinase / Q000172:deficiency / Q000235:genetics
C579071:MX1 protein, human; D008565:Membrane Proteins; D064547:Myxovirus Resistance Proteins; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta; D019892:eIF-2 Kinase; D019204:GTP-Binding Proteins