A Susceptible Mouse Model for Zika Virus Infection
Publication Date
May 05, 2016
Journal
PLOS Neglected Tropical Diseases
Authors
Stuart D. Dowall, Victoria A. Graham, Emma Rayner, Barry Atkinson, et al
Volume
10
Issue
5
Pages
e0004658
DOI
https://dx.plos.org/10.1371/journal.pntd.0004658
Publisher URL
http://journals.plos.org/plosntds/article?id=10.1371%2Fjournal.pntd.0004658
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/27149521
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4858159
Europe PMC
http://europepmc.org/abstract/MED/27149521
Web of Science
000377769300025
Scopus
84971641427
Mendeley
http://www.mendeley.com/research/susceptible-mouse-model-zika-virus-infection
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Mendeley | Further Information

{"title"=>"A Susceptible Mouse Model for Zika Virus Infection", "type"=>"journal", "authors"=>[{"first_name"=>"Stuart D.", "last_name"=>"Dowall", "scopus_author_id"=>"6507446703"}, {"first_name"=>"Victoria A.", "last_name"=>"Graham", "scopus_author_id"=>"36797937700"}, {"first_name"=>"Emma", "last_name"=>"Rayner", "scopus_author_id"=>"36818015900"}, {"first_name"=>"Barry", "last_name"=>"Atkinson", "scopus_author_id"=>"36196253100"}, {"first_name"=>"Graham", "last_name"=>"Hall", "scopus_author_id"=>"7402065364"}, {"first_name"=>"Robert J.", "last_name"=>"Watson", "scopus_author_id"=>"57077622400"}, {"first_name"=>"Andrew", "last_name"=>"Bosworth", "scopus_author_id"=>"56517958100"}, {"first_name"=>"Laura C.", "last_name"=>"Bonney", "scopus_author_id"=>"57200536897"}, {"first_name"=>"Samantha", "last_name"=>"Kitchen", "scopus_author_id"=>"57189518679"}, {"first_name"=>"Roger", "last_name"=>"Hewson", "scopus_author_id"=>"36776805700"}], "year"=>2016, "source"=>"PLoS Neglected Tropical Diseases", "identifiers"=>{"doi"=>"10.1371/journal.pntd.0004658", "issn"=>"19352735", "pmid"=>"27149521", "isbn"=>"1935-2735 (Electronic)\\r1935-2727 (Linking)", "scopus"=>"2-s2.0-84971641427", "pui"=>"610558126", "arxiv"=>"arXiv:1011.1669v3", "sgr"=>"84971641427"}, "id"=>"6be5db3e-9c6f-3347-96d9-3435bb717d46", "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.", "link"=>"http://www.mendeley.com/research/susceptible-mouse-model-zika-virus-infection", "reader_count"=>157, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Professor > Associate Professor"=>8, "Librarian"=>4, "Researcher"=>25, "Student > Doctoral Student"=>12, "Student > Ph. D. Student"=>29, "Student > Postgraduate"=>5, "Student > Master"=>24, "Other"=>9, "Student > Bachelor"=>31, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>2, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Professor > Associate Professor"=>8, "Librarian"=>4, "Researcher"=>25, "Student > Doctoral Student"=>12, "Student > Ph. D. Student"=>29, "Student > Postgraduate"=>5, "Student > Master"=>24, "Other"=>9, "Student > Bachelor"=>31, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>2, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>11, "Agricultural and Biological Sciences"=>53, "Veterinary Science and Veterinary Medicine"=>4, "Chemistry"=>4, "Engineering"=>2, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>16, "Nursing and Health Professions"=>5, "Materials Science"=>1, "Medicine and Dentistry"=>30, "Neuroscience"=>7, "Pharmacology, Toxicology and Pharmaceutical Science"=>3, "Psychology"=>1, "Social Sciences"=>2, "Immunology and Microbiology"=>17}, "reader_count_by_subdiscipline"=>{"Materials Science"=>{"Materials Science"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>30}, "Social Sciences"=>{"Social Sciences"=>2}, "Psychology"=>{"Psychology"=>1}, "Unspecified"=>{"Unspecified"=>11}, "Environmental Science"=>{"Environmental Science"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>3}, "Engineering"=>{"Engineering"=>2}, "Chemistry"=>{"Chemistry"=>4}, "Neuroscience"=>{"Neuroscience"=>7}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>17}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>53}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>5}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>16}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>4}}, "reader_count_by_country"=>{"Netherlands"=>1, "Czech Republic"=>1, "United States"=>2, "Brazil"=>3, "France"=>1, "Portugal"=>1, "Germany"=>1}, "group_count"=>13}

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Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/5146180"], "description"=>"<p>A129 (closed circle) and 129Sv/Ev (closed triangle) mice were subcutaneously inoculated in the lower leg with 10<sup>6</sup> pfu ZIKV and compared to PBS mock-infected A129 (open circle) and 129Sv/Ev (open triangle) groups. <b>(A)</b> Survival analysis of groups presented as Kaplan-Meier survival curves. <b>(B)</b> Weight changes compared to the day of challenge. <b>(C)</b> Temperature changes compared to the day of challenge. <b>(D)</b> Clinical scores of animals. Graphs B-D show the mean values with errors bars denoting standard error. Group sizes were: n = 8 (A129, ZIKV-challenged); n = 8 to day 7 and n = 4 from days 8–14 (129Sv/Ev, ZIKV-challenged); and n = 3 (A129 and 129Sv/Ev, PBS mock-challenged).</p>", "links"=>[], "tags"=>["129 mice", "Susceptible Mouse Model", "RNA", "South American regions", "Zika Virus Infection Zika virus", "ZIKV infection", "model"], "article_id"=>3307939, "categories"=>["Medicine", "Biotechnology", "Science Policy", "Immunology", "Biological Sciences not elsewhere classified", "Mathematical Sciences not elsewhere classified", "Cancer", "Science Policy", "Infectious Diseases", "Virology"], "users"=>["Stuart D. Dowall", "Victoria A. Graham", "Emma Rayner", "Barry Atkinson", "Graham Hall", "Robert J. Watson", "Andrew Bosworth", "Laura C. Bonney", "Samantha Kitchen", "Roger Hewson"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0004658.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/ZIKV_is_virulent_to_IFN-_receptor_deficient_mice_A129_whilst_wild-type_mice_129Sv_Ev_do_not_exhibit_signs_of_disease_/3307939", "title"=>"ZIKV is virulent to IFN-α/β receptor deficient mice (A129) whilst wild-type mice (129Sv/Ev) do not exhibit signs of disease.", "pos_in_sequence"=>1, "defined_type"=>1, "published_date"=>"2016-05-05 07:53:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/5146258"], "description"=>"<p>Histology changes observed in IFN-α/β receptor deficient (A129) and wild-type mice (129Sv/Ev) challenged with ZIKV or mock-challenged with PBS.</p>", "links"=>[], "tags"=>["129 mice", "Susceptible Mouse Model", "RNA", "South American regions", "Zika Virus Infection Zika virus", "ZIKV infection", "model"], "article_id"=>3307996, "categories"=>["Medicine", "Biotechnology", "Science Policy", "Immunology", "Biological Sciences not elsewhere classified", "Mathematical Sciences not elsewhere classified", "Cancer", "Science Policy", "Infectious Diseases", "Virology"], "users"=>["Stuart D. Dowall", "Victoria A. Graham", "Emma Rayner", "Barry Atkinson", "Graham Hall", "Robert J. Watson", "Andrew Bosworth", "Laura C. Bonney", "Samantha Kitchen", "Roger Hewson"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0004658.t001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Histology_changes_observed_in_IFN-_receptor_deficient_A129_and_wild-type_mice_129Sv_Ev_challenged_with_ZIKV_or_mock-challenged_with_PBS_/3307996", "title"=>"Histology changes observed in IFN-α/β receptor deficient (A129) and wild-type mice (129Sv/Ev) challenged with ZIKV or mock-challenged with PBS.", "pos_in_sequence"=>4, "defined_type"=>3, "published_date"=>"2016-05-05 07:53:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/5146207"], "description"=>"<p>Mice were subcutaneously challenged in the lower leg with 10<sup>6</sup> pfu ZIKV. At day 3 and day 6 (A129) or 7 (129Sv/Ev) mice were culled to assess viral load within the circulation and at local sites. Results are denoted as the genome equivalent per ml of blood or per g of tissue. Bars show mean viral RNA levels with error bars denoting standard error. Group sizes were: n = 4 (A129 and 129Sv/Ev, day 3 post-challenge); n = 8 (A129, day 6 post-challenge); and n = 4 (129Sv/Ev, day 7 post-challenge).</p>", "links"=>[], "tags"=>["129 mice", "Susceptible Mouse Model", "RNA", "South American regions", "Zika Virus Infection Zika virus", "ZIKV infection", "model"], "article_id"=>3307957, "categories"=>["Medicine", "Biotechnology", "Science Policy", "Immunology", "Biological Sciences not elsewhere classified", "Mathematical Sciences not elsewhere classified", "Cancer", "Science Policy", "Infectious Diseases", "Virology"], "users"=>["Stuart D. Dowall", "Victoria A. Graham", "Emma Rayner", "Barry Atkinson", "Graham Hall", "Robert J. Watson", "Andrew Bosworth", "Laura C. Bonney", "Samantha Kitchen", "Roger Hewson"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0004658.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Levels_of_ZIKV_viral_RNA_in_blood_brain_ovary_spleen_and_liver_samples_in_IFN-_receptor-deficient_A129_and_wild-type_129Sv_Ev_mice_post-challenge_/3307957", "title"=>"Levels of ZIKV viral RNA in blood, brain, ovary, spleen and liver samples in IFN-α/β receptor-deficient (A129) and wild-type (129Sv/Ev) mice post-challenge.", "pos_in_sequence"=>2, "defined_type"=>1, "published_date"=>"2016-05-05 07:53:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/5146231"], "description"=>"<p>(A) Brain. Animal 23842 (A129, ZIKV-challenged, day 6). Scattered, nuclear fragment in the neuropil of the cerebral cortex (circled). Inset, higher magnification of nuclear debris. (B) Brain. Animal 23811 (A129, ZIKV-challenged, day 6). Lymphocyte infiltration of meninges and perivascular cuffing of meningeal vessels surrounding the cerebral cortex. Inset, degenerate and fragmented nuclei. (C) Brain. Animal 23962 (A129, ZIKV-challenged, day 6). Prominent, perivascular cuffing of small vessels in the neuropil, with infiltration of polymorphonuclear leukocytes (arrows) and presence of scattered, nuclear fragments (arrowheads). H&E. (D) Brain. Animal 23842 (A129, ZIKV-challenged, day 6). Scattered, shrunken, hyper-eosinophilic cells (arrows) amongst the neurons of the hippocampus. Inset, Animal 23798 (129Sv/Ev, PBS, day 14). Normal neurons. (E) Spleen. Animal 23800 (A129, ZIKV-challenged, day 6). Poorly defined white pulp with large, irregular germinal centres. Inset, Animal 23798 (129Sv/Ev, PBS, day 14). Well defined germinal centres within the white pulp (F) Spleen, red pulp. Animal 23800 (A129, ZIKV-challenged, day 6). Numerous, mature neutrophils within the red pulp (circled). (F) Liver. Animal 23836 (A129, ZIKV-challenged, day 6). Small foci of extra-medullary haematopoiesis scattered randomly throughout the parenchyma.</p>", "links"=>[], "tags"=>["129 mice", "Susceptible Mouse Model", "RNA", "South American regions", "Zika Virus Infection Zika virus", "ZIKV infection", "model"], "article_id"=>3307975, "categories"=>["Medicine", "Biotechnology", "Science Policy", "Immunology", "Biological Sciences not elsewhere classified", "Mathematical Sciences not elsewhere classified", "Cancer", "Science Policy", "Infectious Diseases", "Virology"], "users"=>["Stuart D. Dowall", "Victoria A. Graham", "Emma Rayner", "Barry Atkinson", "Graham Hall", "Robert J. Watson", "Andrew Bosworth", "Laura C. Bonney", "Samantha Kitchen", "Roger Hewson"], "doi"=>"https://dx.doi.org/10.1371/journal.pntd.0004658.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Pathological_findings_in_ZIKV_challenged_A129_mice_/3307975", "title"=>"Pathological findings in ZIKV challenged A129 mice.", "pos_in_sequence"=>3, "defined_type"=>1, "published_date"=>"2016-05-05 07:53:47"}

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Relative Metric

{"start_date"=>"2016-01-01T00:00:00Z", "end_date"=>"2016-12-31T00:00:00Z", "subject_areas"=>[]}
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