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Am J Trop Med Hyg. 2016 Jun 1;94(6):1362-9. doi: 10.4269/ajtmh.16-0111. Epub 2016 Mar 28.

Characterization of a Novel Murine Model to Study Zika Virus.

Author information

1
Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas; Department of Pathology, University of Texas Medical Branch, Galveston, Texas; Institute for Translational Science, University of Texas Medical Branch, Galveston, Texas; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas; Department of Biology, New Mexico State University, Las Cruces, New Mexico slrossi@utmb.edu.
2
Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas; Department of Pathology, University of Texas Medical Branch, Galveston, Texas; Institute for Translational Science, University of Texas Medical Branch, Galveston, Texas; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas; Department of Biology, New Mexico State University, Las Cruces, New Mexico.

Abstract

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.

PMID:
27022155
PMCID:
PMC4889758
DOI:
10.4269/ajtmh.16-0111
[Indexed for MEDLINE]
Free PMC Article

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