Characterization of a novel murine model to study zika virus

Shannan Rossi, Robert B. Tesh, Sasha R. Azar, Antonio E. Muruato, Kathryn A. Hanley, Albert J. Auguste, Rose Langsjoen, Slobodan Paessler, Nikos Vasilakis, Scott Weaver

Research output: Contribution to journalArticle

253 Citations (Scopus)

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 107 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.

Original languageEnglish (US)
Pages (from-to)1362-1369
Number of pages8
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume94
Issue number6
DOIs
StatePublished - Jun 1 2016

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Viremia
Disease Outbreaks
Interferon alpha-beta Receptor
Microcephaly
Interferon Type I
Sick Leave
Mortality
Zika Virus
Tremor
Nervous System Diseases
Culicidae
Interferon-gamma
Antiviral Agents
Testis
Weight Loss
Fever
Vaccines
Spleen
Newborn Infant
Morbidity

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases
  • Virology

Cite this

Characterization of a novel murine model to study zika virus. / Rossi, Shannan; Tesh, Robert B.; Azar, Sasha R.; Muruato, Antonio E.; Hanley, Kathryn A.; Auguste, Albert J.; Langsjoen, Rose; Paessler, Slobodan; Vasilakis, Nikos; Weaver, Scott.

In: American Journal of Tropical Medicine and Hygiene, Vol. 94, No. 6, 01.06.2016, p. 1362-1369.

Research output: Contribution to journalArticle

Rossi, Shannan ; Tesh, Robert B. ; Azar, Sasha R. ; Muruato, Antonio E. ; Hanley, Kathryn A. ; Auguste, Albert J. ; Langsjoen, Rose ; Paessler, Slobodan ; Vasilakis, Nikos ; Weaver, Scott. / Characterization of a novel murine model to study zika virus. In: American Journal of Tropical Medicine and Hygiene. 2016 ; Vol. 94, No. 6. pp. 1362-1369.
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