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A Susceptible Mouse Model for Zika Virus Infection
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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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“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]
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“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].”
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Citations
Cites
Smithburn, K. C. (1952) · The Journal of Immunology · doi:10.4049/jimmunol.69.2.223 · Cited by 3,553
Zika Virus Outbreak on Yap Island, Federated States of Micronesia
Duffy, M. R., Chen, T.-H., Hancock, W. T., Powers, A. M., Kool, J. L., Lanciotti, R. S., Pretrick, M., Marfel, M., Holzbauer, S., Dubray, C. L., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0805715 · Cited by 3,130
Zika Virus Associated with Microcephaly
Mlakar, J., Korva, M., Tul, N., Popović, M., Poljšak-Prijatelj, M., Mraz, J., Kolenc, M., Resman Rus, K., Vesnaver Vipotnik, T., Fabjan Vodušek, V., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1600651 · Cited by 2,884
Zika Virus (I). Isolations and serological specificity
Dick, G. W. A., Kitchen, S. F., & Haddow, A. J. (1952) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/0035-9203(52)90042-4 · Cited by 2,698
Self-citationFunctional Role of Type I and Type II Interferons in Antiviral Defense
Müller, U., Steinhoff, U., Reis, L. F. L., Hemmi, S., Pavlovic, J., Zinkernagel, R. M., & Aguet, M. (1994) · Science · doi:10.1126/science.8009221 · Cited by 2,453
Lanciotti, R. S., Kosoy, O. L., Laven, J. J., Velez, J. O., Lambert, A. J., Johnson, A. J., Stanfield, S. M., & Duffy, M. R. (2008) · Emerging infectious diseases · doi:10.3201/eid1408.080287 · Cited by 2,173
Hughes, R. A., & Cornblath, D. R. (2005) · The Lancet · doi:10.1016/s0140-6736(05)67665-9 · Cited by 1,679
First report of autochthonous transmission of Zika virus in Brazil
Zanluca, C., Melo, V. C. A. D., Mosimann, A. L. P., Santos, G. I. V. D., Santos, C. N. D. D., & Luz, K. (2015) · Memórias do Instituto Oswaldo Cruz · doi:10.1590/0074-02760150192 · Cited by 1,320
Melo, A. S. O., Malinger, G., Ximenes, R., Szejnfeld, P. O., Sampaio, S. A., & de Filippis, A. M. B. (2016) · Ultrasound in Obstetrics and Gynecology · doi:10.1002/uog.15831 · Cited by 1,180
Zika Virus Outbreak, Bahia, Brazil
Campos, G. S., Bandeira, A. C., & Sardi, S. I. (2015) · Emerging infectious diseases · doi:10.3201/eid2110.150847 · Cited by 1,150
Oehler, E., Watrin, L., Larre, P., Leparc-Goffart, I., Lastère, S., Valour, F., Baudouin, L., Mallet, H., Musso, D., & Ghawche, F. (2014) · Eurosurveillance · doi:10.2807/1560-7917.es2014.19.9.20720 · Cited by 1,046
Population Incidence of Guillain-Barré Syndrome: A Systematic Review and Meta-Analysis
Sejvar, J. J., Baughman, A. L., Wise, M. P., & Morgan, O. W. (2011) · Neuroepidemiology · doi:10.1159/000324710 · Cited by 959
Zika Virus, French Polynesia, South Pacific, 2013
Cao‐Lormeau, V., Roche, C., Teissier, A., Robin, E., Berry, A.-L., Mallet, H., Sall, A. A., & Musso, D. (2014) · Emerging infectious diseases · doi:10.3201/eid2006.140138 · Cited by 876
Zika virus : A report on three cases of human infection during an epidemic of jaundice in Nigeria
Macnamara, F. N. (1954) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/0035-9203(54)90006-1 · Cited by 771
Detection of Zika Virus in Urine
Gourinat, A.-C., O’Connor, O., Calvez, E., Goarant, C., & Dupont‐Rouzeyrol, M. (2014) · Emerging infectious diseases · doi:10.3201/eid2101.140894 · Cited by 766
Zika virus (II). Pathogenicity and physical properties
Dick, G. W. A. (1952) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/0035-9203(52)90043-6 · Cited by 690
Rapid spread of emerging Zika virus in the Pacific area
Musso, D., Nilles, E. J., & Cao‐Lormeau, V. (2014) · Clinical Microbiology and Infection · doi:10.1111/1469-0691.12707 · Cited by 686
Isolation of Zika Virus from Aedes Aegypti Mosquitoes in Malaysia
Marchette, N. J., Garcia, R., & Rudnick, A. (1969) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.1969.18.411 · Cited by 634
Zika virus in Brazil and macular atrophy in a child with microcephaly
Ventura, C. V. O. C., Maia, M., Bravo-Filho, V., Gois, A. L., & Belfort, R. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00006-4 · Cited by 566
Simpson, D. I. H. (1964) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/0035-9203(64)90201-9 · Cited by 512
Anticipating the international spread of Zika virus from Brazil
Bogoch, I. I., Brady, O. J., Kraemer, M. U. G., German, M. L., Creatore, M., Kulkarni, M. A., Brownstein, J. S., Mekaru, S. R., Hay, S. I., Groot, E., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00080-5 · Cited by 464
Zika Virus, French Polynesia, South Pacific, 2013
Cao‐Lormeau, V. (2014) · Emerging infectious diseases · doi:10.3201/eid2011.141380 · Cited by 448
Zika virus, a cause of fever in Central Java, Indonesia
Olson, J. G., Ksiazek, T. G., Suhandiman, & Triwibowo (1981) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/0035-9203(81)90100-0 · Cited by 445
Zika virus: following the path of dengue and chikungunya?
Musso, D., Cao‐Lormeau, V., & Gubler, D. J. (2015) · The Lancet · doi:10.1016/s0140-6736(15)61273-9 · Cited by 403
Detection of Zika Virus in Semen
Atkinson, B., Hearn, P., Afrough, B., Lumley, S., Carter, D. P., Aarons, E., Simpson, A. J. H., Brooks, T. J. G., & Hewson, R. (2016) · Emerging infectious diseases · doi:10.3201/eid2205.160107 · Cited by 361
Self-citationZika virus infections in Nigeria: virological and seroepidemiological investigations in Oyo State
Fagbami, A. H. (1979) · Journal of Hygiene · doi:10.1017/s0022172400025997 · Cited by 360
Zika Virus Transmission from French Polynesia to Brazil
Musso, D. (2015) · Emerging infectious diseases · doi:10.3201/eid2110.151125 · Cited by 353
Zika virus: following the path of dengue and chikungunya?
Isl, M., States, F. M., Isl, S., Isl, F., Isl, N., & Isl, T. C. (2015) · Cited by 328
Influence of infection during pregnancy on fetal development
Adams Waldorf, K. M., & McAdams, R. M. (2013) · Reproduction · doi:10.1530/rep-13-0232 · Cited by 319
Haddow, A. J., Williams, M., Woodall, J. P., Simpson, D. I. H., & Goma, L. K. H. (1964) · Europe PMC (PubMed Central) · Cited by 300
Zika Virus: Diagnostics for an Emerging Pandemic Threat
Waggoner, J. J., & Pinsky, B. A. (2016) · Journal of Clinical Microbiology · doi:10.1128/jcm.00279-16 · Cited by 262
Mosquitoes Inoculate High Doses of West Nile Virus as They Probe and Feed on Live Hosts
Styer, L. M., Kent, K. A., Albright, R. G., Bennett, C. J., Kramer, L. D., & Bernard, K. A. (2007) · PLoS Pathogens · doi:10.1371/journal.ppat.0030132 · Cited by 240
A sero-epidemiological survey for certain arboviruses (Togaviridae) in Pakistan
Darwish, M. A., Hoogstraal, H., Roberts, T. J., Ahmed, I. P., & Omar, F. (1983) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/0035-9203(83)90106-2 · Cited by 237
Zika virus infection experimentally induced in a human volunteer
Bearcroft, W. G. C. (1956) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/0035-9203(56)90090-6 · Cited by 224
Zika virus infection of the central nervous system of mice
Bell, T., Field, E. J., & Narang, H. K. (1971) · Archives of Virology · doi:10.1007/bf01249709 · Cited by 213
Birth Outcomes Following West Nile Virus Infection of Pregnant Women in the United States: 2003-2004
O’Leary, D. R., Kuhn, S., Kniss, K. L., Hinckley, A. F., Rasmussen, S. A., Pape, W. J., Kightlinger, L. K., Beecham, B. D., Miller, T. K., Neitzel, D. F., et al. (2006) · PEDIATRICS · doi:10.1542/peds.2005-2024 · Cited by 213
Yellow fever and Zika virus epizootics and enzootics in Uganda
McCrae, A. W. R., & Kirya, B. G. (1982) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/0035-9203(82)90161-4 · Cited by 201
Bonthius, D. J. (2012) · Seminars in Pediatric Neurology · doi:10.1016/j.spen.2012.02.002 · Cited by 193
Bereczky, S., Lindegren, G., Karlberg, H., Åkerström, S., Klingström, J., & Mirazimi, A. (2010) · Journal of General Virology · doi:10.1099/vir.0.019034-0 · Cited by 169
Feeding behaviour and sporozoite ejection by infected Anopheles stephensi
Ponnudurai, T., Lensen, A. H. W., van Gemert, G. J. A., Bolmer, M., & Meuwissen, J. H. E. T. (1991) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/0035-9203(91)90012-n · Cited by 166
Intrauterine West Nile Virus Infection—New York, 2002
(2003) · JAMA · doi:10.1001/jama.289.3.295 · Cited by 164
Zika virus: Further isolations in the zika area, and some studies on the strains isolated
Weinbren, M. P., & Williams, M. (1958) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/0035-9203(58)90085-3 · Cited by 154
Buttigieg, K. R., Dowall, S., Findlay‐Wilson, S., Aleksandra, M., Rayner, E. L., Hewson, R., & Carroll, M. W. (2014) · PLoS ONE · doi:10.1371/journal.pone.0091516 · Cited by 146
Self-citationCongenital cytomegalovirus infection: patterns of fetal brain damage
Gabrielli, L., Bonasoni, M. P., Santini, D., Piccirilli, G., Chiereghin, A., Petrisli, E., Dolcetti, R., Guerra, B., Piccioli, M., Lanari, M., et al. (2012) · Clinical Microbiology and Infection · doi:10.1111/j.1469-0691.2012.03983.x · Cited by 124
Guillain–Barré Syndrome—A Classical Autoimmune Disease Triggered by Infection or Vaccination
Israeli, E., Agmon‐Levin, N., Blank, M., Chapman, J., & Shoenfeld, Y. (2010) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-010-8213-3 · Cited by 117
Zika virus spreads across Americas as concerns mount over birth defects
Dyer, O. (2015) · BMJ · doi:10.1136/bmj.h6983 · Cited by 103
Partidos, C. D., Paykel, J., Weger‐Lucarelli, J., Borland, E. M., Powers, A. M., Seymour, R. L., Weaver, S. C., Stinchcomb, D. T., & Osorio, J. E. (2012) · Vaccine · doi:10.1016/j.vaccine.2012.04.099 · Cited by 102
Zika and microcephaly: causation, correlation, or coincidence?
Tetro, J. A. (2016) · Microbes and Infection · doi:10.1016/j.micinf.2015.12.010 · Cited by 95
Cerebral injury in perinatally HIV-infected children compared to matched healthy controls
Cohen, S., Caan, M. W. A., Mutsaerts, H. J. M. M., Scherpbier, H. J., Kuijpers, T. W., Reiss, P., Majoie, C. B. L. M., & Pajkrt, D. (2015) · Neurology · doi:10.1212/wnl.0000000000002209 · Cited by 74
Dowall, S., Findlay‐Wilson, S., Rayner, E. L., Pearson, G., Pickersgill, J., Rule, A., Merredew, N., Smith, H., Chamberlain, J., & Hewson, R. (2011) · Journal of General Virology · doi:10.1099/vir.0.038455-0 · Cited by 69
Self-citationChristofferson, R. C. (2016) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.15-0866 · Cited by 68
Developments in Varicella Zoster Virus Vasculopathy
Nagel, M. A., & Gilden, D. (2016) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-015-0614-5 · Cited by 67
Entry routes for Zika virus in Brazil after 2014 world cup: New possibilities
Salvador, F. S., & Fujita, D. M. (2015) · Travel Medicine and Infectious Disease · doi:10.1016/j.tmaid.2015.10.004 · Cited by 66
Comparative Studies of some African Arboviruses in Cell Culture and in Mice
Way, H. J., Bowen, E. T. W., & Platt, G. S. (1976) · Journal of General Virology · doi:10.1099/0022-1317-30-1-123 · Cited by 64
Milatović, D., Zhang, Y., Olson, S. J., Montine, K. S., Roberts, L. J., Morrow, J. D., Montine, T. J., Dermody, T. S., & Vályi-Nagy, T. (2002) · Journal of NeuroVirology · doi:10.1080/13550280290100743 · Cited by 52
First US case of Zika virus infection is identified in Texas
McCarthy, M. C. (2016) · BMJ · doi:10.1136/bmj.i212 · Cited by 48
Seymour, R. L., Rossi, S. L., Bergren, N. A., Plante, K. S., & Weaver, S. C. (2013) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.12-0674 · Cited by 47
Plante, K. S., Rossi, S. L., Bergren, N. A., Seymour, R. L., & Weaver, S. C. (2015) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0004007 · Cited by 45
Holzer, G. W., Coulibaly, S., Aichinger, G., Savidis-Dacho, H., Mayrhofer, J., Brunner, S., Schmid, K., Kistner, O., Aaskov, J., Falkner, F. G., et al. (2011) · Vaccine · doi:10.1016/j.vaccine.2011.03.089 · Cited by 35
Transmission of Schistosoma haematobium by Bulinus sp. in the KE district of the Gold Coast
McCullough, F. S. (1956) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/0035-9203(56)90091-8 · Cited by 35
Aoki, K., Shimada, S., Simantini, D. S., Tun, M. M. N., Buerano, C. C., Morita, K., & Hayasaka, D. (2014) · Virology Journal · doi:10.1186/1743-422x-11-105 · Cited by 26
Electron micrographs of erythrocytes from Swiss albino mice infected with Zika virus.
Rl, R., Sc, C., & BRUECKNER, A. L. (1955) · PubMed · Cited by 9
Jayasundara, V. K., & Pathiratne, A. (2008) · Bulletin of Environmental Contamination and Toxicology · doi:10.1007/s00128-008-9392-y · Cited by 8
A case of suspected congenital rubella encephalopathy
Inomata, K., Yoshioka, T., Nakamura, K., Ohyama, M., Ohyama, I., Izumi, K., Hirabayashi, K., & Tokito, S. (1980) · Brain and Development · doi:10.1016/s0387-7604(80)80053-2 · Cited by 1
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Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection
Stettler, K., Beltramello, M., Espinosa, D. A., Graham, V., Cassotta, A., Bianchi, S., Zatta, F., Minola, A., Jaconi, S., Mele, F., et al. (2016) · Science · doi:10.1126/science.aaf8505 · Cited by 750
Self-citationKrauer, F., Riesen, M., Revéiz, L., Oladapo, O. T., Martínez-Vega, R. A., Porgo, T. V., Haefliger, A., Broutet, N. J. N., Low, N. N., & WHO Zika Causality Working Group (2017) · PLoS Medicine · doi:10.1371/journal.pmed.1002203 · Cited by 517
A single mutation in the prM protein of Zika virus contributes to fetal microcephaly
Yuan, L., Huang, X., Liu, Z., Zhang, F., Zhu, X., Yu, J.-Y., Ji, X., Xu, Y., Li, G., Li, C., et al. (2017) · Science · doi:10.1126/science.aam7120 · Cited by 482
Vaginal Exposure to Zika Virus during Pregnancy Leads to Fetal Brain Infection
Yockey, L. J., Varela, L., Rakib, T., Khoury-Hanold, W., Fink, S. L., Stutz, B., Szigeti‐Buck, K., van den Pol, A. N., Lindenbach, B. D., Horváth, T. L., et al. (2016) · Cell · doi:10.1016/j.cell.2016.08.004 · Cited by 358
Zika virus — reigniting the TORCH
Coyne, C. B., & Lazear, H. M. (2016) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2016.125 · Cited by 355
Metadata
- 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
- 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
- gold
- doi.org
- 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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