scholarly journals Zika virus infection during development impairs the formation of corpus callosum by disturbing axon guidance and growth of callosal neurons.

2021 ◽  
Author(s):  
Raissa Rilo Christoff ◽  
Jefferson H. Quintanilha ◽  
Raiane O Ferreira ◽  
Jessica C. C. G. Ferreira ◽  
Daniel Menezes Guimaraes ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Axon Guidance ◽  
Birth Defects ◽  
Zika Virus ◽  
In Utero ◽  
Mouse Embryos ◽  
Rna Seq ◽  
Zikv Infection ◽  
Density Reduction ◽  
Congenital Zika Syndrome

Congenital Zika Syndrome (CZS) is a set of birth defects caused by Zika virus (ZIKV) infection during pregnancy. Microcephaly is its main feature, but other brain abnormalities are found in CZS patients, such as ventriculomegaly, brain calcifications, and dysgenesis of the corpus callosum. Many studies have focused on microcephaly, but it remains unknown how ZIKV infection leads to callosal malformation. To tackle this issue, we infected mouse embryos in utero with Brazilian ZIKV and found that they are born with a reduction in callosal area and density of callosal neurons. ZIKV infection also causes a density reduction of PH3+ cells, intermediate progenitor cells and SATB2+ neurons. Moreover, axonal tracing revealed that callosal axons are reduced and misrouted. Also, ZIKV infected cultures show a reduction of callosal axon length. GFAP labelling showed that in utero infection compromises glial cells responsible for midline axon guidance. The RNA-Seq data from infected brains identified downregulation of axon guidance and axonogenesis related genes. In sum, we showed that ZIKV infection impairs critical steps of corpus callosum formation by disrupting not only neurogenesis but also axon guidance and growth across the midline.

scholarly journals Association between Genetic Variants in NOS2 and TNF Genes with Congenital Zika Syndrome and Severe Microcephaly

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 325
Author(s):  
Julia A. Gomes ◽  
Eduarda Sgarioni ◽  
Juliano A. Boquett ◽  
Ana Cláudia P. Terças-Trettel ◽  
Juliana H. da Silva ◽  
...  
Keyword(s):  
Risk Factors ◽  
Zika Virus ◽  
Genetic Variants ◽  
Educational Level ◽  
Congenital Anomalies ◽  
Family Income ◽  
First Trimester ◽  
In Utero ◽  
Zikv Infection ◽  
Congenital Zika Syndrome

Zika virus (ZIKV) causes Congenital Zika Syndrome (CZS) in individuals exposed prenatally. Here, we investigated polymorphisms in VEGFA, PTGS2, NOS3, TNF, and NOS2 genes as risk factors to CZS. Forty children with CZS and forty-eight children who were in utero exposed to ZIKV infection, but born without congenital anomalies, were evaluated. Children with CZS were predominantly infected by ZIKV in the first trimester (p < 0.001) and had mothers with lower educational level (p < 0.001) and family income (p < 0.001). We found higher risk of CZS due the allele rs2297518[A] of NOS2 (OR = 2.28, CI 95% 1.17–4.50, p = 0.015). T allele and TT/CT genotypes of the TNF rs1799724 and haplotypes associated with higher expression of TNF were more prevalent in children with CZS and severe microcephaly (p = 0.029, p = 0.041 and p = 0.030, respectively). Our findings showed higher risk of CZS due ZIKV infection in the first trimester and suggested that polymorphisms in NOS2 and TNF genes affect the risk of CZS and severe microcephaly.

scholarly journals Zika viruses of both African and Asian lineages cause fetal harm in a vertical transmission model

2018 ◽  
Author(s):  
Anna S. Jaeger ◽  
Reyes A. Murreita ◽  
Lea R. Goren ◽  
Chelsea M. Crooks ◽  
Ryan V. Moriarty ◽  
...  
Keyword(s):  
Mouse Model ◽  
Vertical Transmission ◽  
Birth Defects ◽  
Asian American ◽  
Zika Virus ◽  
French Polynesia ◽  
Transmission Model ◽  
Foreseeable Future ◽  
Zikv Infection ◽  
Congenital Zika Syndrome

AbstractCongenital Zika virus (ZIKV) infection was first linked to birth defects during the American outbreak 1–3. It has been proposed that mutations unique to the Asian/American-genotype explain, at least in part, the ability of Asian/American ZIKV to cause congenital Zika syndrome (CZS) 4,5. Recent studies identified mutations in ZIKV infecting humans that arose coincident with the outbreak in French Polynesia and were stably maintained during subsequent spread to the Americas 5. Here we show that African ZIKV can infect and harm fetuses and that the S139N mutation that has been associated with the American outbreak is not essential for fetal harm. Our findings, in a vertical transmission mouse model, suggest that ZIKV will remain a threat to pregnant women for the foreseeable future, including in Africa, southeast Asia, and the Americas. Additional research is needed to better understand the risks associated with ZIKV infection during pregnancy, both in areas where the virus is newly endemic and where it has been circulating for decades.

scholarly journals Persistence of Zika virus RNA in the epididymis of the male reproductive tract

2020 ◽  
Author(s):  
Megan B. Vogt ◽  
Francesca Frere ◽  
Seth A. Hawks ◽  
Claudia E. Perez ◽  
Sheryl Coutermarsh-Ott ◽  
...  
Keyword(s):  
Birth Defects ◽  
Persistent Infection ◽  
Zika Virus ◽  
Reproductive Tract ◽  
Infectious Virus ◽  
Sexual Transmission ◽  
In Utero ◽  
Zikv Infection ◽  
Male Reproductive Tract ◽  
Health Decisions

ABSTRACTZika virus (ZIKV) can infect developing fetuses in utero and cause severe congenital defects. This in utero transmission can occurs following ZIKV infection during pregnancy via sexual transmission or mosquito bite. Infected men may shed ZIKV RNA in semen for over six months post symptom onset, indicating that ZIKV may persistently infect the male reproductive tract (MRT). However, the site of persistent infection in the MRT and whether ZIKV can recrudesce in the MRT is unknown. We hypothesized that if ZIKV establishes a persistent infection in the MRT, then immunosuppressant treatment should stimulate ZIKV replication. We tested this hypothesis in a wild-type mouse model of ZIKV sexual transmission. Male mice were infected with ZIKV and immunosuppressed when they no longer shed infectious virus in their ejaculates. After immunosuppression, ejaculates and MRT tissues were monitored for infectious virus and ZIKV RNA. Our results show that ZIKV recrudescence did not occur following immunosuppression, as we did not detect significant levels of infectious virus in ejaculates or MRT tissues following immunosuppression. We did detect ZIKV RNA in the epididymides of mice treated with the immunosuppressant cyclophosphamide. Further analysis revealed that this ZIKV RNA was contained within the lumen of the epididymis. Our findings suggest that ZIKV persistently infects the epididymis within the male reproductive tract. This study provides insight into the mechanisms behind ZIKV sexual transmission, which may inform public health decisions regarding ZIKV risks.ImportanceZika virus (ZIKV) is an emerging mosquito-transmitted virus that typically causes mild and self-limiting febrile illness in humans; however, during the recent epidemic of ZIKV in the Americas, severe birth defects, such as microcephaly and club foot, were reported in infants born to ZIKV infected mothers. Additionally, sexual transmission has been identified as a secondary method of ZIKV transmission. Since ZIKV can be isolated from semen of infected men long after initial infection, it is imperative to understand the mechanism(s) of ZIKV infection of the male reproductive tract to prevent sexual transmission and ZIKV-associated birth defects. The significance of our research is in identifying a site of persistent ZIKV infection in the male reproductive tract and in assessing the likelihood that a persistently infected individual will begin shedding infectious virus in semen again. This information will enhance our understanding of ZIKV sexual transmission and inform health decisions regarding ZIKV risks.

scholarly journals 1874. Comparison of the Risk of Birth Defects in Live Births From Pregnant Women Infected and Not Infected by Zika Virus in Guadeloupe, 2016–2017

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S47-S47
Author(s):  
Anna Louise Funk ◽  
Bruno Hoen ◽  
Benoit Tressières ◽  
Ingrid Vingadassalom ◽  
Eustase Janky ◽  
...  
Keyword(s):  
Cohort Study ◽  
Pregnant Women ◽  
Birth Defects ◽  
Zika Virus ◽  
Growth Curves ◽  
Neurological Complications ◽  
In Utero ◽  
Control Group ◽  
Zikv Infection ◽  
Neurological Abnormalities

Abstract Background In the French Territories in the Americas (FTA), the risk of birth defects possibly associated with Zika virus (ZIKV) infection was estimated at 7% among fetuses/infants in a cohort of 546 women who developed a symptomatic RT-PCR confirmed ZIKV infection during pregnancy (NEJM 2018;378:985–94). There was no concomitant prospective cohort of pregnant women without ZIKV infection to use as a control group. Methods In Guadeloupe, one of the 3 FTAs that participated in the FTA cohort study, pregnant women were recruited at the time of delivery and tested for ZIKV infection. Women who had a confirmed negative IgG serology test for ZIKV at delivery and no other positive ZIKV test during pregnancy were considered to be ZIKV noninfected. Information on the course of the pregnancy was collected retrospectively and outcomes of live born infants of ZIKV noninfected women were analyzed, using the same definition criteria as those used for the FTA cohort study. Pregnancy outcomes were compared with those of the 241 ZIKV-exposed live born infants in Guadeloupe, extracted from the FTA cohort. Results Of the 490 live born infants without in-utero exposure to ZIKV, 42 infants (8.6%) had neurological abnormalities that were described as “potentially linked to ZIKV infection”; all but one of these were microcephaly without any other brain or clinical abnormalities. The proportion of such abnormalities was not statistically different from that observed in the 241 live born infants with ZIKV exposure (6.6%, P = 0.36). When re-considering the combined 8 fetuses and 241 infants of women with confirmed ZIKV infection in Guadeloupe from the FTA cohort, only two (0.8%) live born infants and three (1.2%) medically aborted fetuses had birth defects that could still be linked to ZIKV infection. Conclusion Isolated anthropometric and other mild neurological abnormalities had the same prevalence among live born infants with and without in utero ZIKV exposure. The high prevalence of isolated microcephaly among ZIKV noninfected women in our study population suggests that the sensitive definition for microcephaly, using a −2 SD cut-off with international growth curves, may lead to an overestimate of the rate of neurological complications of ZIKV infection during pregnancy. Disclosures All Authors: No reported Disclosures.

scholarly journals Asymptomatic Prenatal Zika Virus Infection and Congenital Zika Syndrome

2018 ◽  
Vol 5 (4) ◽  
Author(s):  
Enny S Paixao ◽  
Wei-Yee Leong ◽  
Laura C Rodrigues ◽  
Annelies Wilder-Smith
Keyword(s):  
Virus Infection ◽  
Birth Defects ◽  
Prospective Studies ◽  
Zika Virus ◽  
Retrospective Studies ◽  
Recall Bias ◽  
Virus Infections ◽  
Fetal Outcomes ◽  
Zika Virus Infection ◽  
Congenital Zika Syndrome

Abstract To investigate to what extent asymptomatic vs symptomatic prenatal Zika virus infections contribute to birth defects, we identified 3 prospective and 8 retrospective studies. The ratio varied greatly in the retrospective studies, most likely due to recruitment and recall bias. The prospective studies revealed a ratio of 1:1 for asymptomatic vs symptomatic maternal Zika infections resulting in adverse fetal outcomes.

scholarly journals Zika Virus Pathogenesis: From Early Case Reports to Epidemics

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 886 ◽  
Author(s):  
Ryan D. Pardy ◽  
Martin J. Richer
Keyword(s):  
Risk Factors ◽  
Zika Virus ◽  
Case Reports ◽  
Viral Persistence ◽  
The Body ◽  
Therapeutic Approaches ◽  
Zikv Infection ◽  
Congenital Zika Syndrome ◽  
Early Case ◽  
The Impact

For the first 60 years following its isolation, Zika virus (ZIKV) remained a relatively poorly described member of the Flaviviridae family. However, since 2007, it has caused a series of increasingly severe outbreaks and is now associated with neurological symptoms such as Guillain-Barré syndrome and congenital Zika syndrome (CZS). A number of reports have improved our understanding of rare complications that may be associated with ZIKV infection in adults, the areas of the body to which it spreads, and viral persistence in various tissues. Likewise, studies on the effect of ZIKV infection during pregnancy have identified risk factors for CZS and the impact this syndrome has on early childhood. Understanding these outcomes and the factors that drive ZIKV pathogenesis are key to developing vaccination and therapeutic approaches to avoid these severe and potentially debilitating symptoms.

scholarly journals Congenital Zika syndrome is associated with maternal protein malnutrition

2020 ◽  
Vol 6 (2) ◽  
pp. eaaw6284 ◽  
Author(s):  
J. Barbeito-Andrés ◽  
P. Pezzuto ◽  
L. M. Higa ◽  
A. A. Dias ◽  
J. M. Vasconcelos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brain Size ◽  
Epidemiological Data ◽  
Protein Malnutrition ◽  
Rna Seq ◽  
Zikv Infection ◽  
Postnatal Brain ◽  
Low Protein ◽  
Congenital Zika Syndrome ◽  
Pregnant Mice

Zika virus (ZIKV) infection during pregnancy is associated with a spectrum of developmental impairments known as congenital Zika syndrome (CZS). The prevalence of this syndrome varies across ZIKV endemic regions, suggesting that its occurrence could depend on cofactors. Here, we evaluate the relevance of protein malnutrition for the emergence of CZS. Epidemiological data from the ZIKV outbreak in the Americas suggest a relationship between undernutrition and cases of microcephaly. To experimentally examine this relationship, we use immunocompetent pregnant mice, which were subjected to protein malnutrition and infected with a Brazilian ZIKV strain. We found that the combination of protein restriction and ZIKV infection leads to severe alterations of placental structure and embryonic body growth, with offspring displaying a reduction in neurogenesis and postnatal brain size. RNA-seq analysis reveals gene expression deregulation required for brain development in infected low-protein progeny. These results suggest that maternal protein malnutrition increases susceptibility to CZS.

scholarly journals Clinical Outcomes of a Zika Virus Mother–Child Pair Cohort in Spain

Pathogens ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 352 ◽  
Author(s):  
Antoni Soriano-Arandes ◽  
Marie Antoinette Frick ◽  
Milagros García López-Hortelano ◽  
Elena Sulleiro ◽  
Carlota Rodó ◽  
...  
Keyword(s):  
Zika Virus ◽  
Adverse Outcomes ◽  
Zikv Infection ◽  
Child Pair ◽  
Referral Hospitals ◽  
Congenital Zika Syndrome ◽  
Endemic Areas ◽  
Neurodevelopmental Abnormalities ◽  
Congenital Microcephaly

Background: Zika virus (ZIKV) infection has been associated with congenital microcephaly and other neurodevelopmental abnormalities. There is little published research on the effect of maternal ZIKV infection in a non-endemic European region. We aimed to describe the outcomes of pregnant travelers diagnosed as ZIKV-infected in Spain, and their exposed children. Methods: This prospective observational cohort study of nine referral hospitals enrolled pregnant women (PW) who travelled to endemic areas during their pregnancy or the two previous months, or those whose sexual partners visited endemic areas in the previous 6 months. Infants of ZIKV-infected mothers were followed for about two years. Results: ZIKV infection was diagnosed in 163 PW; 112 (70%) were asymptomatic and 24 (14.7%) were confirmed cases. Among 143 infants, 14 (9.8%) had adverse outcomes during follow-up; three had a congenital Zika syndrome (CZS), and 11 other potential Zika-related outcomes. The overall incidence of CZS was 2.1% (95%CI: 0.4–6.0%), but among infants born to ZIKV-confirmed mothers, this increased to 15.8% (95%CI: 3.4–39.6%). Conclusions: A nearly 10% overall risk of neurologic and hearing adverse outcomes was found in ZIKV-exposed children born to a ZIKV-infected traveler PW. Longer-term follow-up of these children is needed to assess whether there are any later-onset manifestations.

scholarly journals Prevalence of individual brain and eye defects potentially related to Zika virus in pregnancy in 22 U.S. states and territories, January 2016 - June 2017

2022 ◽  
Author(s):  
Augustina Delaney ◽  
Samantha M. Olson ◽  
Nicole M. Roth ◽  
Janet D. Cragan ◽  
Shana Godfred-Cato ◽  
...  
Keyword(s):  
Birth Defects ◽  
Zika Virus ◽  
Cortical Atrophy ◽  
Zikv Infection ◽  
Live Births ◽  
Prevalence Estimates ◽  
Surveillance Programs ◽  
Prevalence Ratios ◽  
Cerebral Cortical Atrophy ◽  
In Pregnancy

Abstract During the Centers for Disease Control and Prevention’s Zika Virus Response, birth defects surveillance programs adapted to monitor birth defects potentially related to Zika virus (ZIKV) infection during pregnancy. Pregnancy outcomes occurring during January 2016-June 2017 in 22 U.S. states and territories were used to estimate the prevalence of those brain and eye defects potentially related to ZIKV. Jurisdictions were divided into three groups: areas with widespread ZIKV transmission, areas with limited local ZIKV transmission, and areas without local ZIKV transmission. Prevalence estimates for selected brain and eye defects and microcephaly per 10,000 live births were estimated. Prevalence ratios (PRs) and 95% confidence intervals (CIs) were estimated using Poisson regression for areas with widespread and limited ZIKV transmission compared to areas without local ZIKV transmission. Defects with significantly higher prevalence in areas of widespread transmission were pooled, and PRs were calculated by quarter, comparing subsequent quarters to the first quarter (January – March 2016). Nine defects had significantly higher prevalence in areas of widespread transmission. The highest PRs were seen in intracranial calcifications (PR=12.6, 95% CI [7.4, 21.3]), chorioretinal abnormalities (12.5 [7.1, 22.3]), brainstem abnormalities (9.3, [4.7, 18.4]), and cerebral/cortical atrophy (6.7, [4.2, 10.8]). The PR of the nine pooled defects was significantly higher in three quarters in areas with widespread transmission. The largest difference in prevalence was observed for defects consistently reported in infants with congenital ZIKV infection. Birth defects surveillance programs could consider monitoring a subset of birth defects potentially related to ZIKV in pregnancy.

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