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Cited by 322Mosquito-borne diseases and controlViral Infections and VectorsViral Infections and Outbreaks Research

Characterization of Lethal Zika Virus Infection in AG129 Mice

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Aliota, Matthew T., Caine, Elizabeth A., Walker, Emma C., Larkin, Katrina E., Camacho, Erwin, Osorio, Jorge E.·2016·PLoS neglected tropical diseases
DOI 10.1371/journal.pntd.0004682PMC PMC4836712
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Abstract

BACKGROUND: Mosquito-borne Zika virus (ZIKV) typically causes a mild and self-limiting illness known as Zika fever, which often is accompanied by maculopapular rash, headache, and myalgia. During the current outbreak in South America, ZIKV infection during pregnancy has been hypothesized to cause microcephaly and other diseases. The detection of ZIKV in fetal brain tissue supports this hypothesis. Because human infections with ZIKV historically have remained sporadic and, until recently, have been limited to small-scale epidemics, neither the disease caused by ZIKV nor the molecular determinants of virulence and/or pathogenicity have been well characterized. Here, we describe a small animal model for wild-type ZIKV of the Asian lineage. METHODOLOGY/PRINCIPAL FINDINGS: Using mice deficient in interferon α/β and Ɣ receptors (AG129 mice), we report that these animals were highly susceptible to ZIKV infection and disease, succumbing within seven to eight days. Rapid viremic dissemination was observed in visceral organs and brain; but only was associated with severe pathologies in the brain and muscle. Finally, these results were consistent across challenge routes, age of mice, and inoculum doses. These data represent a mouse model for ZIKV that is not dependent on adapting ZIKV to intracerebral passage in mice. CONCLUSIONS/SIGNIFICANCE: Foot pad injection of AG129 mice with ZIKV represents a biologically relevant model for studying ZIKV infection and disease development following wild-type virus inoculation without the requirement for adaptation of the virus or intracerebral delivery of the virus. This newly developed Zika disease model can be exploited to identify determinants of ZIKV virulence and reveal molecular mechanisms that control the virus-host interaction, providing a framework for rational design of acute phase therapeutics and for vaccine efficacy testing.

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Crossref · 10.1371/journal.pntd.0004682

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  • Nonhuman primates are suitable for studying ZIKV pathogenesis and therapeutics/vaccine development but are expensive.

    “Although NHPs are suitable for studying ZIKV pathogenesis and therapeutics/vaccine development, they are expensive [21].”

    From ICR suckling mouse model of Zika virus infection for disease modeling and drug validation (2018) · cites this paper as [21]

    The Introduction says nonhuman primate models may be sufficient for ZIKV vaccine and therapeutic testing, and that they are prohibitively expensive for studies of pathogenesis and vaccinology. The citing sentence accurately conveys the expense but states their suitability as certain where the source hedges it. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • 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 [21]

    The Methods (Mice; page not provided) identify AG129 mice as deficient in interferon receptors, and the Results and Discussion (ZIKV infection is fatal for AG129 mice; page not provided) report illness and mortality after ZIKV infection. The copy does not establish susceptibility to different ZIKV strains or address Irf3/5/7 TKO mice. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • 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 [21]

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Authors
Aliota, M. T., Caine, E. A., Walker, E. C., Larkin, K. E., Camacho, E., & Osorio, J. E.
Affiliations
University of Wisconsin–Madison (US)
Corresponding author
Osorio, Jorge E.
ORCID
Venue
PLoS neglected tropical diseases
Publisher
Public Library of Science (PLoS)
Published
2016-04-19
Volume
10
Issue
4
Pages
e0004682
ISSN
  • 1935-2727 (ISSN-L)
  • 1935-2735
DOI
10.1371/journal.pntd.0004682
PMC
PMC4836712
OpenAlex
W2338703441
Cited by
322
References
45
Citations by year
2026: 10 · 2025: 12 · 2024: 16 · 2023: 19 · 2022: 19 · 2021: 25 · 2020: 28 · 2019: 37 · 2018: 50 · 2017: 63 · 2016: 42
FWCI
63.46
Type
journal article
Language
en
Update notices
correction (2016-05-23)
Open access
Licence
Locations
  • PLoS neglected tropical diseases (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Repositorio Institucional Universidad de Sucre (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institute of Allergy and Infectious Diseases (R21 AI117413-01, T32AI055397)
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, AG129 mice, virulence factors, viremia, neuropathology, muscle pathology, mosquito-borne arboviruses, vaccine efficacy evaluation, microcephaly
MeSH terms
Zika Virus Infection, Interferon gamma Receptor, Animals, Brain, Death, Disease Models, Animal, Muscles, Viremia, Receptors, Interferon, Mice, Knockout, Mice, Receptor, Interferon alpha-beta

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