Characterization of a Novel Murine Model to Study Zika Virus
Open accessAbstract
The mosquito-borne Zika virus (ZIKV) is responsible for an explosive ongoing outbreak of febrile illness across the Americas. ZIKV was previously thought to cause only a mild, flu-like illness, but during the current outbreak, an association with Guillain-Barré syndrome and microcephaly in neonates has been detected. A previous study showed that ZIKV requires murine adaptation to generate reproducible murine disease. In our study, a low-passage Cambodian isolate caused disease and mortality in mice lacking the interferon (IFN) alpha receptor (A129 mice) in an age-dependent manner, but not in similarly aged immunocompetent mice. In A129 mice, viremia peaked at ∼10(7) plaque-forming units/mL by day 2 postinfection (PI) and reached high titers in the spleen by day 1. ZIKV was detected in the brain on day 3 PI and caused signs of neurologic disease, including tremors, by day 6. Robust replication was also noted in the testis. In this model, all mice infected at the youngest age (3 weeks) succumbed to illness by day 7 PI. Older mice (11 weeks) showed signs of illness, viremia, and weight loss but recovered starting on day 8. In addition, AG129 mice, which lack both type I and II IFN responses, supported similar infection kinetics to A129 mice, but with exaggerated disease signs. This characterization of an Asian lineage ZIKV strain in a murine model, and one of the few studies reporting a model of Zika disease and demonstrating age-dependent morbidity and mortality, could provide a platform for testing the efficacy of antivirals and vaccines.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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 [30]
The Introduction identifies AG129 mice as immunocompromised, and the Results section on partial paralysis reports ZIKV infection, neurological disease, and death in infected three-week-old AG129 mice. The paper does not study Irf3/5/7 TKO mice, and its AG129 findings concern one Cambodian ZIKV isolate rather than different strains. (LLM, conf=0.90)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Mackenzie, J. S., Gubler, D. J., & Petersen, L. R. (2004) · Nature Medicine · doi:10.1038/nm1144 · Cited by 1,314 · see citing works
Biology of Zika Virus Infection in Human Skin Cells
Hamel, R., Dejarnac, O., Wichit, S., Ekchariyawat, P., Neyret, A., Luplertlop, N., Perera-Lecoin, M., Surasombatpattana, P., Talignani, L., Frédéric Thomas, A., et al. (2015) · Journal of Virology · doi:10.1128/jvi.00354-15 · Cited by 1,199 · see citing works
Potential Sexual Transmission of Zika Virus
Musso, D., Roche, C., Robin, E., Nhan, T., Teissier, A., & Cao‐Lormeau, V. (2015) · Emerging infectious diseases · doi:10.3201/eid2102.141363 · Cited by 1,174 · see citing works
Probable Non–Vector-borne Transmission of Zika Virus, Colorado, USA
Foy, B. D., Kobylinski, K. C., Foy, J. C., Blitvich, B. J., da Rosa, A. T., Haddow, A. D., Lanciotti, R. S., & Tesh, R. B. (2011) · Emerging infectious diseases · doi:10.3201/eid1705.101939 · Cited by 1,157 · see citing works
Self-citationPossible Association Between Zika Virus Infection and Microcephaly — Brazil, 2015
Schüler‐Faccini, L., Ribeiro, E. M., Feitosa, I. M. L., Horovitz, D. D. G., Cavalcanti, D. P., Pessoa, A. L. S., Doriqui, M. J. R., Neri, J. I., Neto, J. M. D. P., Wanderley, H. Y. C., et al. (2016) · MMWR Morbidity and Mortality Weekly Report · doi:10.15585/mmwr.mm6503e2 · Cited by 1,076 · see citing works
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 1,015 · see citing works
Hayes, E. B. (2009) · Emerging infectious diseases · doi:10.3201/eid1509.090442 · Cited by 889 · see citing works
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 · see citing works
Genetic Characterization of Zika Virus Strains: Geographic Expansion of the Asian Lineage
Haddow, A. D., Schuh, A. J., Yasuda, C. Y., Kasper, M. R., Heang, V., Huy, R., Guzmán, H., Tesh, R. B., & Weaver, S. C. (2012) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0001477 · Cited by 773 · see citing works
Self-citationDetection 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 · see citing works
Musso, D., Nhan, T., Robin, E., Roche, C., Bierlaire, D., Zisou, K., Yan, A. S., Cao‐Lormeau, V., & Broult, J. (2014) · Eurosurveillance · doi:10.2807/1560-7917.es2014.19.14.20761 · Cited by 699 · see citing works
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 · see citing works
Detection of Zika virus in saliva
Musso, D., Roche, C., Nhan, T., Robin, E., Teissier, A., & Cao‐Lormeau, V. (2015) · Journal of Clinical Virology · doi:10.1016/j.jcv.2015.04.021 · Cited by 522 · see citing works
Zika Virus, French Polynesia, South Pacific, 2013
Cao‐Lormeau, V. (2014) · Emerging infectious diseases · doi:10.3201/eid2011.141380 · Cited by 455 · see citing works
An adenosine nucleoside inhibitor of dengue virus
Yin, Z. Q., Chen, Y., Schul, W., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0907010106 · Cited by 390 · see citing works
Shresta, S., Kyle, J. L., Snider, H. M., Basavapatna, M., Beatty, P. R., & Harris, E. (2004) · Journal of Virology · doi:10.1128/jvi.78.6.2701-2710.2004 · Cited by 320 · see citing works
Zika Virus Infection, Cambodia, 2010
Heang, V., Yasuda, C. Y., Sovann, L., et al. (2012) · Emerging infectious diseases · doi:10.3201/eid1802.111224 · Cited by 255 · see citing works
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 · see citing works
Interim Guidelines for Prevention of Sexual Transmission of Zika Virus — United States, 2016
Oster, A. M., Brooks, J. T., Stryker, J. E., et al. (2016) · MMWR Morbidity and Mortality Weekly Report · doi:10.15585/mmwr.mm6505e1 · Cited by 209 · see citing works
Plante, K. S., Wang, E., Partidos, C. D., et al. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002142 · Cited by 178 · see citing works
Cytokine kinetics of Zika virus-infected patients from acute to reconvalescent phase
Tappe, D., Pérez-Girón, J. V., Zammarchi, L., Rissland, J., Ferreira, D. F., Jaenisch, T., Gómez‐Medina, S., Günther, S., Bartoloni, A., Muñoz‐Fontela, C., et al. (2015) · Medical Microbiology and Immunology · doi:10.1007/s00430-015-0445-7 · Cited by 160 · see citing works
A Mouse Model for Studying Viscerotropic Disease Caused by Yellow Fever Virus Infection
Meier, K. C., Gardner, C. L., Khoretonenko, M. V., Klimstra, W. B., & Ryman, K. D. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000614 · Cited by 157 · see citing works
Concern over Zika virus grips the world
Samarasekera, U., & Triunfol, M. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00257-9 · Cited by 144 · see citing works
Shirley, D.-A. T., & Nataro, J. P. (2017) · Pediatric Clinics of North America · doi:10.1016/j.pcl.2017.03.012 · Cited by 116 · see citing works
Fatal Sickle Cell Disease and Zika Virus Infection in Girl from Colombia
Arzuza-Ortega, L., Polo, A., Pérez-Tatis, G., López-García, H., Parra, E., Pardo-Herrera, L. C., Rico-Turca, A. M., Villamil-Gómez, W., & Rodríguez-Morales, A. J. (2016) · Emerging infectious diseases · doi:10.3201/eid2205.151934 · Cited by 113 · see citing works
Prestwood, T. R., Morar, M. M., Zellweger, R. M., et al. (2012) · Journal of Virology · doi:10.1128/jvi.06743-11 · Cited by 111 · see citing works
PERSISTENT SHEDDING OF WEST NILE VIRUS IN URINE OF EXPERIMENTALLY INFECTED HAMSTERS
Tonry, J. H., XIAO, S.-Y., Siirin, M., et al. (2005) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.2005.72.320 · Cited by 107 · see citing works
Lobigs, M., Müllbacher, A., Wang, Y., Pavy, M., & Lee, E. (2003) · Journal of General Virology · doi:10.1099/vir.0.18654-0 · Cited by 95 · see citing works
West Nile Virus Detection in Urine
Tonry, J. H., Brown, C. B., Cropp, C. B., et al. (2005) · Emerging infectious diseases · doi:10.3201/eid1108.050238 · Cited by 66 · see citing works
Paessler, S., Yun, N., Judy, B., Dziuba, N., Zacks, M., Grund, A. H., Frolov, I., Campbell, G., Weaver, S., & Estes, D. M. (2007) · Virology · doi:10.1016/j.virol.2007.05.041 · Cited by 66 · see citing works
Self-citationLever, M. S., Piercy, T. J., Steward, J. A., et al. (2011) · Journal of Medical Microbiology · doi:10.1099/jmm.0.036210-0 · Cited by 59 · see citing works
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 · see citing works
Self-citationInfectious Chikungunya Virus in the Saliva of Mice, Monkeys and Humans
Gardner, J., Rudd, P. A., Prow, N. A., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0139481 · Cited by 45 · see citing works
Ryman, K. D., Meier, K. C., Gardner, C. L., Adegboyega, P. A., & Klimstra, W. B. (2007) · Virology · doi:10.1016/j.virol.2007.06.039 · Cited by 44 · see citing works
Thibodeaux, B. A., Garbino, N. C., Liss, N. M., et al. (2012) · Vaccine · doi:10.1016/j.vaccine.2012.03.003 · Cited by 43 · see citing works
Seymour, R. L., Adams, A. P., Leal, G., et al. (2015) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0003800 · Cited by 42 · see citing works
IRES-based Venezuelan equine encephalitis vaccine candidate elicits protective immunity in mice
Rossi, S. L., Guerbois, M., Gorchakov, R. V., et al. (2013) · Virology · doi:10.1016/j.virol.2012.11.013 · Cited by 39 · see citing works
Self-citationKondo, M., Akachi, S., Ando, K., et al. (2016) · The Journal of Dermatology · doi:10.1111/1346-8138.13253 · Cited by 8 · see citing works
Vestergaard, B. F., & SCHERER, W. F. (1971) · PubMed · Cited by 5 · see citing works
Zika Virus- A Global Health Emergency
Rabindran, R., & Gedam, D. D. S. (2016) · Tropical Journal of Pathology and Microbiology · doi:10.17511/jopm.2016.i01.01 · Cited by 1 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The Brazilian Zika virus strain causes birth defects in experimental models
Cugola, F. R., Fernandes, I. R., Russo, F. B., Freitas, B. C., Dias, J. L. M., Guimarães, K. P., Benazzato, C., Almeida, N., Pignatari, G. C., Romero, S., et al. (2016) · Nature · doi:10.1038/nature18296 · Cited by 1,326 · see citing works
A Mouse Model of Zika Virus Pathogenesis
Lazear, H. M., Govero, J., Smith, A. M., Platt, D. J., Fernandez, E., Miner, J. J., & Diamond, M. S. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.03.010 · Cited by 909 · see citing works
Dang, J., Tiwari, S. K., Lichinchi, G., Qin, Y., Patil, V. S., Eroshkin, A. M., & Rana, T. M. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.04.014 · Cited by 731 · see citing works
Wu, K.-Y., Zuo, G.-L., Li, X.-F., Ye, Q., Deng, Y.-Q., Huang, X.-Y., Cao, W.-C., Qin, C.-F., & Luo, Z.-G. (2016) · Cell Research · doi:10.1038/cr.2016.58 · Cited by 283 · see citing works
Animal Models of Zika Virus Infection, Pathogenesis, and Immunity
Morrison, T. E., & Diamond, M. S. (2017) · Journal of Virology · doi:10.1128/jvi.00009-17 · Cited by 275 · see citing works
Vaccine Mediated Protection Against Zika Virus-Induced Congenital Disease
Richner, J. M., Jagger, B. W., Shan, C., Fontes, C. R., Dowd, K. A., Cao, B., Himansu, S., Caine, E. A., Nunes, B. T. D., Medeiros, D. B. A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.06.040 · Cited by 267 · see citing works
Self-citationBroadly Neutralizing Activity of Zika Virus-Immune Sera Identifies a Single Viral Serotype
Dowd, K. A., DeMaso, C. R., Pelc, R. S., Speer, S. D., Smith, A. R. Y., Goo, L., Platt, D. J., Mascola, J. R., Graham, B. S., Mulligan, M. J., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.07.049 · Cited by 206 · see citing works
Emerging Role of Zika Virus in Adverse Fetal and Neonatal Outcomes
Panchaud, A., Stojanov, M., Ammerdorffer, A., Vouga, M., & Baud, D. (2016) · Clinical Microbiology Reviews · doi:10.1128/cmr.00014-16 · Cited by 171 · see citing works
Erasmus, J. H., Khandhar, A. P., Guderian, J., Granger, B., Archer, J., Archer, M., Gage, E., Fuerte-Stone, J., Larson, E., Lin, S., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2018.07.010 · Cited by 161 · see citing works
Szaba, F. M., Tighe, M., Kummer, L. W., Lanzer, K. G., Ward, J. M., Lanthier, P., Kim, I.-J., Kuki, A., Blackman, M. A., Thomas, S. J., et al. (2018) · PLoS Pathogens · doi:10.1371/journal.ppat.1006994 · Cited by 97 · see citing works
Duggal, N. K., Ritter, J. M., McDonald, E. M., Romo, H., Guirakhoo, F., Davis, B. S., Chang, G.-J. J., & Brault, A. C. (2017) · The American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.17-0263 · Cited by 52 · see citing works
ICR suckling mouse model of Zika virus infection for disease modeling and drug validation
Wu, Y.-H., Tseng, C.-K., Lin, C.-K., Wei, C.-K., Lee, J.-C., & Young, K.-C. (2018) · PLoS Neglected Tropical Diseases · doi:10.1371/journal.pntd.0006848 · Cited by 35 · see citing works
Overview on the Current Status of Zika Virus Pathogenesis and Animal Related Research
Pawitwar, S. S., Dhar, S., Tiwari, S., Ojha, C. R., Lapierre, J., Martins, K., Rodzinski, A., Parira, T., Paudel, I., Li, J., et al. (2017) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-017-9743-8 · Cited by 30 · see citing works
- Authors
- Rossi, S. L., Tesh, R. B., Azar, S. R., Muruato, A. E., Hanley, K. A., Auguste, A. J., Langsjoen, R. M., Paessler, S., Vasilakis, N., & Weaver, S. C.
- Affiliations
- New Mexico State University (US)
- Corresponding author
- Rossi, Shannan L.
- ORCID
- Venue
- The American Society of Tropical Medicine and Hygiene
- Published
- 2016-06-01
- Volume
- 94
- Issue
- 6
- Pages
- 1362-1369
- ISSN
- 0002-9637 (ISSN-L)
- 1476-1645
- PMC
- PMC4889758
- OpenAlex
- W2321791060
- Cited by
- 458
- References
- 44
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 18 · 2023: 14 · 2022: 18 · 2021: 28 · 2020: 51 · 2019: 60 · 2018: 73 · 2017: 102 · 2016: 78
- FWCI
- 103.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Tropical Medicine and Hygiene (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Homeland Security
- New Mexico State University
- Georgia Clinical and Translational Science Alliance
- National Institutes of Health (GM103451, TR001439, UL1TR001439)
- National Institute of General Medical Sciences (P20GM103451)
- National Institute of Allergy and Infectious Diseases (R24AI120942)
- National Center for Research Resources (P20RR016480)
- National Center for Advancing Translational Sciences (CTSA – UL1TR001439, TR001439)
- 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 model, interferon alpha receptor, AG129 mice, age-related diseases, viremia, neurological disorders, microcephaly, Guillain-Barré syndrome
- MeSH terms
- Zika Virus Infection, Zika Virus, Animals, Disease Models, Animal, Disease Susceptibility, Immunohistochemistry, Mice, Inbred Strains, Vero Cells, Virus Replication, Viral Load, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
