Abstract
In 2015, ZIKV infection attracted international attention during an epidemic in the Americas, when neurological disorders were reported in infants who had their mothers exposed to ZIKV during pregnancy. World Health Organization (WHO) epidemiological data show that 5 to 15% of neonates exposed to ZIKV in the uterus have complications included in abnormalities related to Congenital Zika Syndrome (CZS). The risk of complications after birth is not well documented, however, clinical evidence shows that 6% of infants exposed to ZIKV during pregnancy have complications present at birth, and this rate rises to 14% when medical monitoring is performed in all exposed infants, regardless of birth condition. Thus, the evaluation and monitoring of all exposed infants are of foremost importance as the development of late complications has been increasingly supported by clinical evidence. The identification of changes in protein profile of infants exposed to ZIKV without CZS could provide valuable findings to better understand molecular changes in this cohort. Here, we use a shotgun-proteomics approach to investigate alterations in the serum of infants without CZS symptoms but exposed to intrauterine ZIKV (ZIKV) compared to unexposed controls (CTRL). A complex pattern of differentially expressed proteins was identified, highlighting the dysregulation of proteins involved in axon orientation, visual phototransduction, and global protease activity in children exposed to ZIKV without CZS. These data support the importance of monitoring children exposed to ZIKV during gestation and without early CZS symptoms. Our study is the first to assess molecular evidence of possible late disorders in children victims of the ZIKV outbreak in the Americas. We emphasize the importance of medical monitoring of symptomatic and asymptomatic children, as apparently unexplained late neurological and eye disorders may be due to intrauterine ZIKV exposure.
Highlights
Zika is a single-stranded RNA virus belonging to the Flaviviridae family that was first isolated in 1947 from a rhesus monkey in Kampala, Uganda (Dick et al, 1952)
The serum of infants without symptoms of congenital Zika syndrome (CZS), but with intrauterine exposure to Zika virus (ZIKV) and unexposed controls was evaluated by a proteomic approach based on mass spectrometry, with and without depletion of the 14 most abundant serum proteins (Figure 1A)
After the occurrence of isolated cases of venous thrombosis in patients who had a positive diagnosis for ZIKV, Ramacciotti et al (2019) assessed blood D-dimer levels, which are usually monitored for the diagnosis of deep venous thrombosis, of 172 patients who had ZIKV or chikungunya, without cross-infection
Summary
Zika is a single-stranded RNA virus belonging to the Flaviviridae family that was first isolated in 1947 from a rhesus monkey in Kampala, Uganda (Dick et al, 1952). The vectors of these viruses are infected mosquitoes, responsible for the spread of important diseases such as dengue fever, West Nile fever, and yellow fever (Noorbakhsh et al, 2019). In 2015, Zika virus infection attracted international attention during an epidemic in the Americas (Venancio et al, 2019), due to its association with increasing cases of microcephaly, congenital malformation and other neurological disorders in newborns who had their mothers infected during pregnancy (Kindhauser et al, 2016; Mlakar et al, 2016). Data published by the Brazilian Ministry of Health indicate 14,558 suspected cases of congenital microcephaly and others central nervous system (CNS) malformations between 2015 and 2017 (Pan American Health Organization/World Health Organization, 2017)
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