title: Hazara virus infection is lethal for adult type I interferon receptor-knockout mice and may act as a surrogate for infection with the human-pathogenic Crimean-Congo hemorrhagic fever virus.
abstract: Hazara virus (HAZV) is closely related to the Crimean-Congo hemorrhagic fever virus (CCHFV). HAZV has not been reported to cause human disease; work with infectious material can be carried out at containment level (CL)-2. By contrast, CCHFV causes a haemorrhagic fever in humans and requires CL-4 facilities. A disease model of HAZV infection in mice deficient in the type I interferon receptor is reported in this study. Dose-response effects were seen with higher doses, resulting in a shorter time to death and earlier detection of viral loads in organs. The lowest dose of 10 p.f.u. was still lethal in over 50 % of the mice. Histopathological findings were identified in the liver, spleen and lymph nodes, with changes similar to a recent mouse model of CCHFV infection. The findings demonstrate that inoculation of mice with HAZV may act as a useful surrogate model for the testing of antiviral agents against CCHFV.
authors.affiliation: Health Protection Agency, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Dowall
authors.affiliation: Health Protection Agency, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Findlay-Wilson
authors.affiliation: Health Protection Agency, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Rayner
authors.affiliation: Health Protection Agency, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
authors.forename: Geoff
authors.initials: G
authors.lastname: Pearson
authors.affiliation: Health Protection Agency, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
authors.forename: Janice
authors.initials: J
authors.lastname: Pickersgill
authors.affiliation: Health Protection Agency, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
authors.forename: Antony
authors.initials: A
authors.lastname: Rule
authors.affiliation: Health Protection Agency, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
authors.forename: Natasha
authors.initials: N
authors.lastname: Merredew
authors.affiliation: Health Protection Agency, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
authors.forename: Hazel
authors.initials: H
authors.lastname: Smith
authors.affiliation: Health Protection Agency, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
authors.forename: John
authors.initials: J
authors.lastname: Chamberlain
authors.affiliation: Health Protection Agency, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
authors.forename: Roger
authors.initials: R
authors.lastname: Hewson
mesh_terms: D000825:Animal Structures / Q000473:pathology / Q000821:virology; D000818:Animals; D004195:Disease Models, Animal; D017353:Gene Deletion; D003225:Hemorrhagic Fever Virus, Crimean-Congo / Q000276:immunology* / Q000472:pathogenicity*; D006479:Hemorrhagic Fever, Crimean / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D006651:Histocytochemistry; D006801:Humans; D008099:Liver / Q000473:pathology / Q000821:virology; D008198:Lymph Nodes / Q000473:pathology / Q000821:virology; D051379:Mice; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000276:immunology*; D013154:Spleen / Q000473:pathology / Q000821:virology; D016019:Survival Analysis; D019562:Viral Load
chemical_list: D053633:Receptor, Interferon alpha-beta