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Cited by 323Mosquito-borne diseases and controlViral Infections and VectorsViral Infections and Outbreaks Research

A Susceptible Mouse Model for Zika Virus Infection

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Dowall, Stuart D., Graham, Victoria A., Rayner, Emma, Atkinson, Barry, Hall, Graham, Watson, Robert J., Bosworth, Andrew, Bonney, Laura C. +2 more·2016·PLoS neglected tropical diseases
DOI 10.1371/journal.pntd.0004658PMC PMC4858159

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Abstract

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 viral RNA being detected widespread 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 to those seen in A129 mice. Our results identify A129 mice as being highly susceptible to ZIKV and thus a suitable small animal model for the testing of vaccines and antivirals which are urgently required. Author summary Since first being recognised in 1947, Zika virus (ZIKV) has mainly been a mild illness with symptoms including a limited fever and rash. In 2007 the virus spread from Africa into French Polynesia and then onwards across Pacific regions and into South America. In these new regions, ZIKV has been associated with more severe clinical conditions including Gullain-Barre syndrome and microcephaly. There are no currently approved antivirals or vaccines available with proven activity against ZIKV, and the World Health Organisation declared the spread of ZIKV as a Public Health Emergency of International Concern. Here, we have used a mouse strain with a deficiency in the type-I interferon receptor (A129) and shown that they are susceptible to ZIKV infection after inoculation that closely resembles the natural route via mosquito bite. Although A129 mice are deficient in the innate interferon response, they retain their adaptive immunity and thus have successfully been used as suitable models for the testing of vaccinations and antivirals. Our study provides details on a suitable model for the testing of future interventions against ZIKV.

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  • Small animal models are a better choice for studying ZIKV.

    “In this regard, small animal models are a better choice for studying ZIKV [10, 21].”

    From ICR suckling mouse model of Zika virus infection for disease modeling and drug validation (2018) · cites this paper as [10]

  • AG129 and Irf3/5/7 TKO mice are immunocompromised, permissive to different ZIKV strains, and vulnerable to ZIKV-related pathology and lethality.

    “AG129 and Irf3/5/7 TKO mice are the immunocompromised mice which were permissive to different strain ZIKV infection and vulnerable to ZIKV-relative pathology and lethality [10, 21, 30, 31].”

    From ICR suckling mouse model of Zika virus infection for disease modeling and drug validation (2018) · cites this paper as [10]

    The Methods and Results study A129 mice, not the named AG129 or Irf3/5/7 TKO mice. The Discussion says the A129 model was tested with one ZIKV strain, MP1751, and that comparisons across strains were future work. Our copy therefore does not establish the attributed susceptibility, pathology, or lethality for either named mouse model. (LLM, conf=0.78)

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Authors
Dowall, S. D., Graham, V. A., Rayner, E., Atkinson, B., Hall, G., Watson, R. J., Bosworth, A., Bonney, L. C., Kitchen, S., & Hewson, R.
Affiliations
Public Health England (GB)
Corresponding author
  • Dowall, Stuart D.
  • Graham, Victoria A.
  • Rayner, Emma
  • Atkinson, Barry
  • Hall, Graham
  • Watson, Robert J.
  • Bosworth, Andrew
  • Bonney, Laura C.
  • Kitchen, Samantha
  • Hewson, Roger
ORCID
Venue
PLoS neglected tropical diseases
Publisher
Public Library of Science (PLoS)
Published
2016-05-05
Volume
10
Issue
5
Pages
e0004658
ISSN
  • 1935-2727 (ISSN-L)
  • 1935-2735
DOI
10.1371/journal.pntd.0004658
PMC
PMC4858159
OpenAlex
W2345638947
Cited by
323
References
65
Citations by year
2026: 7 · 2025: 10 · 2024: 9 · 2023: 10 · 2022: 13 · 2021: 44 · 2020: 31 · 2019: 42 · 2018: 50 · 2017: 70 · 2016: 36
FWCI
65.45
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS neglected tropical diseases (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Public Health England (Not applicable)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
  • Health Sciences › Medicine › Infectious Diseases › Viral Infections and Vectors
  • Health Sciences › Medicine › Infectious Diseases › Viral Infections and Outbreaks Research
Keywords
Zika virus, mouse infection model, subcutaneous challenge, mosquito bites, vaccine testing, microcephaly, Guillain-Barré syndrome, histopathology
MeSH terms
Zika Virus Infection, Zika Virus, Animals, Brain, Disease Models, Animal, Disease Susceptibility, Female, RNA, Viral, Mice, Knockout, Mice, Receptor, Interferon alpha-beta

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