Abstract
Human infants with congenital Zika virus (ZIKV) infection exhibit a range of symptoms including microcephaly, intracranial calcifications, macular atrophy and arthrogryposis. More importantly, prognosis data have lagged far behind the recent outbreak of ZIKV in 2015. In this work, we allow congenitally ZIKV-infected mice to grow into puberty. These mice exhibited motor incoordination and visual dysfunctions, which can be accounted by anatomical defects in the retina and cerebellar cortex. In contrary, anxiety level of the ZIKV-infected mice is normal. The spectrum of anatomical and behavioral deficits is consistent across different mice. Our data provided evidence that may help predict the public health burden in terms of prognosis of ZIKV-related congenital brain malformations in an animal model. Our study provided behavioral evaluation for the prognosis of congenital ZIKV infection and provides a platform for screening and evaluation of drugs candidates and treatment aiming at improving regeneration of infected neurons to prevent sequelae caused by ZIKV infection of fetus.
Highlights
The first human case of Zika virus (ZIKV) infection was published in 1952 (Dick, 1952)
Observations from earlier studies of congenital ZIKV infection show that embryos that were intra-ventricle infected at E13.5 do not survive after birth (Li et al, 2016b)
We showed that brains of ZIKV-infected mice were smaller than those of mock-infected mice at P0 (Fig. 1b and c) (Cugola et al, 2016; Miner et al, 2016a), suggesting growth restriction of ZIKV-infected mice at infant
Summary
The first human case of Zika virus (ZIKV) infection was published in 1952 (Dick, 1952). Up to 2007, only 14 human cases of ZIKV infection had been confirmed (Fagbami, 1979; Moore et al, 1975; Olson et al, 1981). Since late 2015, ZIKV infection has swept across N35 countries and territories in Caribbean and South America (Fauci and Morens, 2016) after originating from an outbreak in Brazil (Campos et al, 2015). Of greater concern is an upsurge of cases and studies indicating a causal role between the ZIKV outbreak and an increased number of neonates in Brazil with birth defects, such as microcephaly and intrauterine growth restriction (IUGR) (Rasmussen et al, 2016; Heymann et al, 2016; Mlakar et al, 2016). Up to now, we have gained very little knowledge about the prognosis of these children with congenital abnormalities due to the very recent outbreak of Zika
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