Congenital Zika syndrome: Pitfalls in the placental barrier

Robinson, Nia; Galvan, Evangelina E. Mayorquin; Trujillo, Isidro G. Zavala; Zavala-Cerna, María Guadalupe

doi:10.1002/rmv.1985

Cited by 19 publications

(23 citation statements)

References 53 publications

(118 reference statements)

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“…The pathophysiology of ZIKV infection and the mechanism of the virus' passage across the placental barrier are still under investigation [48]. The exact timing of placental and fetal infection in relation to maternal viremia is also still unclear, as is the correlation between prolonged viremia and the development of congenital Zika syndrome [48].…”

Section: Plos Onementioning

confidence: 99%

“…Microcephaly is only one of the possible complications found in neonates exposed to ZIKV during pregnancy and comprising the congenital Zika syndrome (CZS) [28,[38][39][40][41]. There is sufficient evidence to support a causal link between ZIKV and congenital anomalies, at both the population and individual levels [38,[42][43][44][45][46][47][48][49].…”

Section: Introductionmentioning

confidence: 99%

“…The systematic reviews published to date have addressed causality, transplacental transmission of ZIKV, the effect of sexual transmission, and antibody-dependent enhancement of viral teratogenicity, a different approach from that of the present review [38,[42][43][44][45][46][47][48][49]. This review aimed to determine the signs and symptoms that characterize the congenital Zika syndrome and contribute to a more accurate and timely diagnosis.…”

Section: Introductionmentioning

confidence: 99%

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Congenital Zika syndrome: A systematic review

et al. 2020

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Background The signs and symptoms of Zika virus infection are usually mild and self-limited. However, the disease has been linked to neurological complications such as Guillain-Barré syndrome and peripheral nerve involvement, and also to abortion and fetal deaths due to vertical transmission, resulting in various congenital malformations in newborns, including microcephaly. This review aimed to describe the o signs and symptoms that characterize the congenital Zika syndrome. Methods and findings A systematic review was performed with a protocol and described according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The search strategy yielded 2,048 studies. After the exclusion of duplicates and application of inclusion criteria, 46 studies were included. The main signs and symptoms associated with the congenital Zika syndrome were microcephaly, parenchymal or cerebellar calcifications, ventriculomegaly, central nervous system hypoplasia or atrophy, arthrogryposis, ocular findings in the posterior and anterior segments, abnormal visual function and low birthweight for gestational age. Conclusions Zika virus infection during pregnancy can cause a series of changes in the growth and development of children, while impacting the healthcare system due to the severity of cases. Our findings outline the disease profile in newborns and infants and may contribute to the development and updating of more specific clinical protocols.

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Section: Plos Onementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Congenital Zika syndrome: A systematic review

et al. 2020

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“…For the majority of the aforementioned teratogenic viruses, an essential determinant of the clinical symptoms of the newborn is the gestational age at which infection occurs, e.g., [35,36,38]. Hereafter, we will outline the similarities and differences of the congenital infections caused by HCMV and ZIKV as opposed to RV.…”

Section: Characteristics Of Congenital Virus Infections In Reference mentioning

confidence: 99%

Pluripotent Stem Cell-Based Models: A Peephole into Virus Infections during Early Pregnancy

Claus

Jung

Hübschen

2020

Cells

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The rubella virus (RV) was the first virus shown to be teratogenic in humans. The wealth of data on the clinical symptoms associated with congenital rubella syndrome is in stark contrast to an incomplete understanding of the forces leading to the teratogenic alterations in humans. This applies not only to RV, but also to congenital viral infections in general and includes (1) the mode of vertical transmission, even at early gestation, (2) the possible involvement of inflammation as a consequence of an activated innate immune response, and (3) the underlying molecular and cellular alterations. With the progress made in the development of pluripotent stem cell-based models including organoids and embryoids, it is now possible to assess congenital virus infections on a mechanistic level. Moreover, antiviral treatment options can be validated, and newly emerging viruses with a potential impact on human embryonal development, such as that recently reflected by the Zika virus (ZIKV), can be characterized. Here, we discuss human cytomegalovirus (HCMV) and ZIKV in comparison to RV as viruses with well-known congenital pathologies and highlight their analysis on current models for the early phase of human development. This includes the implications of their genetic variability and, as such, virus strain-specific properties for their use as archetype models for congenital virus infections. In this review, we will discuss the use of induced pluripotent stem cells (iPSC) and derived organoid systems for the study of congenital virus infections with a focus on their prominent aetiologies, HCMV, ZIKV, and RV. Their assessment on these models will provide valuable information on how human development is impaired by virus infections; it will also add new insights into the normal progression of human development through the analysis of developmental pathways in the context of virus-induced alterations. These are exciting perspectives for both developmental biology and congenital virology.

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“…Within the genus, ZIKV is closely related to other clinically important mosquito-borne flaviviruses, such as dengue (DENV), Japanese encephalitis (JEV), West Nile (WNV), and yellow fever (YFV) viruses, as well as several medically significant tick-borne flaviviruses, including tick-borne encephalitis and Powassan viruses [2]. In humans, ZIKV is spread horizontally by blood-sucking mosquitoes of the genus Aedes (e.g., A. aegypti and A. albopictus) and through sexual contact, but it can also be passed vertically from a pregnant woman to her fetus in utero [3][4][5][6][7][8]. While uncommon, ZIKV transmission can also occur via blood transfusion and breastfeeding [9,10].…”

Section: Introductionmentioning

confidence: 99%

Development, Characterization, and Application of Two Reporter-Expressing Recombinant Zika Viruses

Yun

Song

Woolley

et al. 2020

Viruses

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Zika virus (ZIKV), a mosquito-borne transplacentally transmissible flavivirus, is an enveloped virus with an ~10.8 kb plus-strand RNA genome that can cause neurological disease. To facilitate the identification of potential antivirals, we developed two reporter-expressing ZIKVs, each capable of expressing an enhanced green fluorescent protein or an improved luminescent NanoLuc luciferase. First, a full-length functional ZIKV cDNA clone was engineered as a bacterial artificial chromosome, with each reporter gene under the cap-independent translational control of a cardiovirus-derived internal ribosome entry site inserted downstream of the single open reading frame of the viral genome. Two reporter-expressing ZIKVs were then generated by transfection of ZIKV-susceptible BHK-21 cells with infectious RNAs derived by in vitro run-off transcription from the respective cDNAs. As compared to the parental virus, the two reporter-expressing ZIKVs grew to lower titers with slower growth kinetics and formed smaller foci; however, they displayed a genome-wide viral protein expression profile identical to that of the parental virus, except for two previously unrecognized larger forms of the C and NS1 proteins. We then used the NanoLuc-expressing ZIKV to assess the in vitro antiviral activity of three inhibitors (T-705, NITD-008, and ribavirin). Altogether, our reporter-expressing ZIKVs represent an excellent molecular tool for the discovery of novel antivirals.

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Congenital Zika syndrome: Pitfalls in the placental barrier

Cited by 19 publications

References 53 publications

Congenital Zika syndrome: A systematic review

Congenital Zika syndrome: A systematic review

Pluripotent Stem Cell-Based Models: A Peephole into Virus Infections during Early Pregnancy

Development, Characterization, and Application of Two Reporter-Expressing Recombinant Zika Viruses

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