RESUMEN
Zika virus (ZIKV) is a member of Flaviviridae family that has emerged as a pathogen of significant public health importance. The rapid expansion of ZIKV in the South and Central America has recently gained medical attention emphasizing the capacity of ZIKV to spread to non-endemic regions. ZIKV infection during pregnancy has been demonstrated to cause microcephaly and other fetal developmental abnormalities. An increased incidence of Guillain-Barre syndrome, an immune mediated neuropathy of the peripheral nervous system, has also been reported in ZIKV-infected patients in French Polynesia and Brazil. No effective therapies currently exist for treating patients infected with ZIKV. Despite the relatively short time interval, an intensive effort by the global scientific community has resulted in development of animal models to study multiple aspects of ZIKV biology. Several animal models have been established to investigate pathogenesis of ZIKV in adults, pregnant mothers, and developing fetuses. Here we review the remarkable progress of newly developed small and large animal models for understanding ZIKV pathogenesis.
RESUMEN
BACKGROUND: Animal models are critical to understand disease and to develop countermeasures for the ongoing epidemic of Zika virus (ZIKV). Here we report that immunocompetent guinea pigs are susceptible to infection by a contemporary American strain of ZIKV. METHODS: Dunkin-Hartley guinea pigs were inoculated with 106 plaque-forming units of ZIKV via subcutaneous route and clinical signs were observed. Viremia, viral load in the tissues, anti-ZIKV neutralizing antibody titer, and protein levels of multiple cytokine and chemokines were analyzed using qRT-PCR, plaque assay, plaque reduction neutralization test (PRNT) and multiplex immunoassay. RESULTS: Upon subcutaneous inoculation with PRVABC59 strain of ZIKV, guinea pigs demonstrated clinical signs of infection characterized by fever, lethargy, hunched back, ruffled fur, and decrease in mobility. ZIKV was detected in the whole blood and serum using qRT-PCR and plaque assay. Anti-ZIKV neutralizing antibody was detected in the infected animals using PRNT. ZIKV infection resulted in a dramatic increase in protein levels of multiple cytokines, chemokines and growth factors in the serum. ZIKV replication was observed in spleen and brain, with the highest viral load in the brain. This data demonstrate that after subcutaneous inoculation, the contemporary ZIKV strain is neurotropic in guinea pigs. CONCLUSION: The guinea pig model described here recapitulates various clinical features and viral kinetics observed in ZIKV-infected patients, and therefore may serve as a model to study ZIKV pathogenesis, including pregnancy outcomes and for evaluation of vaccines and therapeutics.