1, 3, 4 Before 2007, reported cases of ZIKV infection (Zika fever) have been sporadic and benign. 1, 2 Relatively little research has been conducted on ZIKV since its first isolation almost 70 years ago from the blood of a sentinel rhesus monkey in the Zika forest of Uganda. Louis encephalitis, Japanese encephalitis, West Nile encephalitis, and tick-borne encephalitis. The Flavivirus genus includes many viruses that produce disease in humans, including dengue, yellow fever, St. Zika virus (ZIKV) is an emerging mosquito-borne pathogen that is part of the Spondweni serocomplex of the genus Flavivirus, family Flaviviridae. 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. 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. Older mice (11 weeks) showed signs of illness, viremia, and weight loss but recovered starting on day 8. In this model, all mice infected at the youngest age (3 weeks) succumbed to illness by day 7 PI. Robust replication was also noted in the testis.
ZIKV was detected in the brain on day 3 PI and caused signs of neurologic disease, including tremors, by day 6. 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. 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. A previous study showed that ZIKV requires murine adaptation to generate reproducible murine disease. 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.
The mosquito-borne Zika virus (ZIKV) is responsible for an explosive ongoing outbreak of febrile illness across the Americas. Below each day, observations and viremia titers are listed. Moribund mice on day 6 were necropsied and organs were harvested, triturated, and titrated. Viral loads in individual intradermal-infected AG129 mice. # Sample not taken and * no detectable titer. BAR = bright, alert, and reactive to stimuli. Below each day, the observations, average titer for the group, and if the mouse was perfused with phosphate-buffered saline before necropsy are listed. Organs were homogenized and titrated on Vero cell monolayers. Viral loads in individual 3-week-old A129 mice. ( B) Viremia titers are shown ( N = 1 for each route for each day except ID inoculated on day 6, N = 3). infected groups on day 5 ( P = 0.0006) by one-factor analysis of variance with Tukey–Kramer post hoc test. * Significance between percent of initial weights from MOCK vs. Groups of three mice aged 3 weeks were weighed daily, and percent of initial weight is reported ( A). Error bars in all panels denote standard errors of the means.įSS13025 is lethal in AG129 by intraperitoneal (IP) or intradermal (ID) inoculation. ( C) The mortality (natural or euthanized) after infection is shown. # Sample not taken and * samples lower than the limit of detection. ( B) Levels of viremia in serum are shown. Each age has 1–2 mice MOCK infected with phosphate-buffered saline. Groups of A129 mice aged 3 weeks ( N = 5), 5 weeks ( N = 6), and 11 weeks ( N = 3) were infected with 1 × 10 5 plaque-forming units of FSS13025 IP. The percent of initial weight is shown, and bars denote standard errors of the means.Ī129 mice show disease in an age-dependent manner. Mice MOCK infected with phosphate-buffered saline ( N = 2) are shown by a dashed line, whereas FSS13025-infected mice ( N = 6) are shown by a solid line. Groups of 3-week-old CD1 mice were infected with 1 × 10 4 plaque-forming units subcutaneously and weighed daily. CD1 infected with Zika virus (ZIKV) strain FSS13025 do not show signs of disease.
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