title: A Susceptible Mouse Model for Zika Virus Infection.
abstract: Zika virus (ZIKV) is a mosquito-borne pathogen which has recently spread beyond Africa and into Pacific and South American regions. Despite first being detected in 1947, very little information is known about the virus, and its spread has been associated with increases in Guillain-Barre syndrome and microcephaly. There are currently no known vaccines or antivirals against ZIKV infection. Progress in assessing interventions will require the development of animal models to test efficacies; however, there are only limited reports on in vivo studies. The only susceptible murine models have involved intracerebral inoculations or juvenile animals, which do not replicate natural infection. Our report has studied the effect of ZIKV infection in type-I interferon receptor deficient (A129) mice and the parent strain (129Sv/Ev) after subcutaneous challenge in the lower leg to mimic a mosquito bite. A129 mice developed severe symptoms with widespread viral RNA detection in the blood, brain, spleen, liver and ovaries. Histological changes were also striking in these animals. 129Sv/Ev mice developed no clinical symptoms or histological changes, despite viral RNA being detectable in the blood, spleen and ovaries, albeit at lower levels than those seen in A129 mice. Our results identify A129 mice as being highly susceptible to ZIKV and thus A129 mice represent a suitable, and urgently required, small animal model for the testing of vaccines and antivirals.
authors.affiliation: National Infection Service, Public Health England, Porton Down, Salisbury, Wiltshire, United Kingdom.
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Dowall
authors.affiliation: National Infection Service, Public Health England, Porton Down, Salisbury, Wiltshire, United Kingdom.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Graham
authors.affiliation: National Infection Service, Public Health England, Porton Down, Salisbury, Wiltshire, United Kingdom.
authors.forename: Emma
authors.initials: E
authors.lastname: Rayner
authors.affiliation: National Infection Service, Public Health England, Porton Down, Salisbury, Wiltshire, United Kingdom.
authors.forename: Barry
authors.initials: B
authors.lastname: Atkinson
authors.affiliation: National Infection Service, Public Health England, Porton Down, Salisbury, Wiltshire, United Kingdom.
authors.forename: Graham
authors.initials: G
authors.lastname: Hall
authors.affiliation: National Infection Service, Public Health England, Porton Down, Salisbury, Wiltshire, United Kingdom.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Watson
authors.affiliation: National Infection Service, Public Health England, Porton Down, Salisbury, Wiltshire, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bosworth
authors.affiliation: National Infection Service, Public Health England, Porton Down, Salisbury, Wiltshire, United Kingdom.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Bonney
authors.affiliation: National Infection Service, Public Health England, Porton Down, Salisbury, Wiltshire, United Kingdom.
authors.forename: Samantha
authors.initials: S
authors.lastname: Kitchen
authors.affiliation: National Infection Service, Public Health England, Porton Down, Salisbury, Wiltshire, United Kingdom.
authors.forename: Roger
authors.initials: R
authors.lastname: Hewson
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000071244:Zika Virus / Q000145:classification* / Q000472:pathogenicity; D000071243:Zika Virus Infection / Q000276:immunology* / Q000473:pathology / Q000821:virology*
chemical_list: C508032:Ifnar1 protein, mouse; D012367:RNA, Viral; D053633:Receptor, Interferon alpha-beta