Answer – Abortion and Zika Virus Congenital Infection

Zika virus (ZIKV) infection during pregnancy causes a wide spectrum of congenital abnormalities and postnatal developmental sequelae such as fetal loss, intrauterine growth restriction (IUGR), microcephaly, or motor and neurodevelopmental disorders. Here, we investigated whether a mouse pregnancy model recapitulated a wide range of symptoms after congenital ZIKV infection, and whether the embryonic age of congenital infection changed the fetal or postnatal outcomes. Infection with ZIKV strain PRVABC59 from embryonic day 6.5 (E6.5) to E8.5, corresponding to the mid-first trimester in humans, caused fetal death, fetal resorption, or severe IUGR, whereas infection from E9.5 to E14.5, corresponding to the late-first to second trimester in humans, caused stillbirth, neonatal death, microcephaly, and postnatal growth deficiency. Furthermore, 4-week-old offspring born to dams infected at E12.5 showed abnormalities in neuropsychiatric state, motor behavior, autonomic function, or reflex and sensory function. Thus, our model recapitulated the multiple symptoms seen in human cases, and the embryonic age of congenital infection was one of the determinant factors of offspring outcomes in mice. Furthermore, maternal neutralizing antibodies protected the offspring from neonatal death after congenital infection at E9.5, suggesting that neonatal death in our model could serve as criteria for screening of vaccine candidates.

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Clinical findings in congenital infection by Zika virus: a retrospective study in a reference hospital in Central-West Brazil

BMC Pediatrics ◽

10.1186/s12887-019-1762-6 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Cláudia de Paula Guimarães ◽

Myrella Silveira Macedo ◽

Maria Alves Barbosa ◽

Solomar Martins Marques ◽

Paulo Sucasas Costa ◽

...

Keyword(s):

Zika Virus ◽

Congenital Infection ◽

Signs And Symptoms ◽

Clinical Findings ◽

Virus Infections ◽

Health Care Teams ◽

Reference Hospital ◽

Congenital Zika Syndrome ◽

The Central Nervous System ◽

Eye Damage

Background An increased number of congenital Zika virus infections with neurological and musculoskeletal malformations have been diagnosed worldwide, however, there are still several gaps in the knowledge about this infection, its associated mechanism, timing of transmission, and description of throughout findings of signs and symptoms, which is described in this paper. The purpose of this study is to describe aspects of congenital Zika syndrome (CZS) beyond the central nervous system comprising detailed delineation of all the other clinical findings. Methods A retrospective research developed using electronic medical records. We analyzed the files of 69 children with an initial diagnosis of microcephaly by Zika vírus who were born in 2015, 2016 and 2017, treated during the period from 2016 to 2017. Results The newborns presented several neurological and musculoskeletal malformations, eye damage, hearing impairment and other malformations. Conclusions The present study has significant impact for health care teams following lactents with Congenital Zika Syndrome.

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Presumed congenital infection by Zika virus: findings on psychomotor development - a case report

Revista Brasileira de Saúde Materno Infantil ◽

10.1590/1806-9304201600s100004 ◽

2016 ◽

Vol 16 (suppl 1) ◽

pp. 39-44 ◽

Cited By ~ 11

Author(s):

Ana Carla Gomes Botelho ◽

Luana Valeriano Neri ◽

Marina Queiroz Ferreira da Silva ◽

Thaisa Teixeira de Lima ◽

Karla Gonçalves dos Santos ◽

...

Keyword(s):

Zika Virus ◽

Motor Performance ◽

Muscle Tone ◽

Congenital Infection ◽

Lower Limbs ◽

Psychomotor Development ◽

Vision Assessment ◽

Motion Range ◽

Functional Vision ◽

Functional Vision Assessment

Abstract Introduction: the identification of Zika virus (ZikV) in the amniotic fluid, in the placenta and in newborns' brains suggests a neurotropism of this agent in the brain development, resulting in neuro-psycho-motor alterations. Thus, this present study reports the assessment of children diagnosed by a congenital infection, presumably by ZikV, followed-up at the Rehabilitation Center Prof. Ruy Neves Baptist at the Instituto de Medicina Integral Prof. Fernando Figueira (IMIP). Description: as proposed by the Ministry of Health, the following instruments were used to evaluate the neuro-motor functions of four children with microcephaly aged between three and four months: The Test of Infant Motor Performance (TIMP); the functional vision assessment; the manual function scale development; and the clinical evaluation protocol on pediatric dysphagia (PAD-PED). Discussion: the children evaluated presented atypical motor performance, muscle tone and spontaneous motricity which encompass the symmetry and the motion range of the upper and lower limbs proven to be altered. The functional vision showed alterations which can cause limitations in the performance of functional activities and the learning process. Regarding to the speech articulator's functions observed that the maturation and coordination of sucking, swallowing and breathing did not yet encounter the appropriate age maturity level.

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Prolonged Shedding of Zika Virus Associated with Congenital Infection

New England Journal of Medicine ◽

10.1056/nejmc1607583 ◽

2016 ◽

Vol 375 (12) ◽

pp. 1202-1204 ◽

Cited By ~ 61

Author(s):

Danielle B.L. Oliveira ◽

Flávia J. Almeida ◽

Edison L. Durigon ◽

Érica A. Mendes ◽

Carla T. Braconi ◽

...

Keyword(s):

Zika Virus ◽

Congenital Infection

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Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study

BMJ ◽

10.1136/bmj.i3182 ◽

2016 ◽

pp. i3182 ◽

Cited By ~ 4

Keyword(s):

Clinical Features ◽

Zika Virus ◽

Case Series ◽

Congenital Infection ◽

Mri Findings ◽

Retrospective Case ◽

Retrospective Case Series ◽

Case Series Study ◽

Series Study ◽

Ct And Mri

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Confirmed case of Zika virus congenital infection, Spain, March 2016

Eurosurveillance ◽

10.2807/1560-7917.es.2016.21.24.30261 ◽

2016 ◽

Vol 21 (24) ◽

Cited By ~ 24

Author(s):

Sonia Perez ◽

Ruben Tato ◽

Jorge Julio Cabrera ◽

Alberto Lopez ◽

Olga Robles ◽

...

Keyword(s):

Pregnant Woman ◽

Amniotic Fluid ◽

Brain Tissue ◽

Umbilical Cord ◽

Zika Virus ◽

Congenital Infection ◽

Arthrogryposis Multiplex Congenita ◽

Ultrasound Scan ◽

Imported Case ◽

Fetal Malformations

We describe Zika virus (ZIKV) vertical transmission in an imported case in Spain, in a 17-week pregnant woman. ZIKV IgG, IgM and RNA were detected in serum in week 17. At 19 weeks, ultrasound scan revealed fetal malformations and ZIKV was detected in the amniotic fluid. Pregnancy was terminated at week 21; autopsy of the fetus revealed bilateral hydrocephalus, brain microcalcifications and arthrogryposis multiplex congenita. ZIKV was detected in the umbilical cord and brain tissue.

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Notice to Readers: Changes in the Presentation of Zika Virus Disease, Non-Congenital Infection, and Addition of Zika Virus Congenital Infection to Notifiable Diseases and Mortality Table I

MMWR Morbidity and Mortality Weekly Report ◽

10.15585/mmwr.mm6520a6 ◽

2016 ◽

Vol 65 (20) ◽

pp. 524-524

Keyword(s):

Zika Virus ◽

Virus Disease ◽

Congenital Infection ◽

Notifiable Diseases ◽

Mortality Table

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Leu-to-Phe substitution at prM146 decreases the growth ability of Zika virus and partially reduces its pathogenicity in mice

Scientific Reports ◽

10.1038/s41598-021-99086-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Takuya Inagaki ◽

Satoshi Taniguchi ◽

Yasuhiro Kawai ◽

Takahiro Maeki ◽

Eri Nakayama ◽

...

Keyword(s):

Amino Acid ◽

Zika Virus ◽

Reverse Genetics ◽

Cultured Cells ◽

Congenital Infection ◽

Febrile Illness ◽

Vero Cells ◽

Lower Growth ◽

Asian Strain ◽

Growth Ability

AbstractZika virus (ZIKV) is a mosquito-borne flavivirus that causes febrile illness. The recent spread of ZIKV from Asia to the Americas via the Pacific region has revealed unprecedented features of ZIKV, including transplacental congenital infection causing microcephaly. Amino acid changes have been hypothesized to underlie the spread and novel features of American ZIKV strains; however, the relationship between genetic changes and the epidemic remains controversial. A comparison of the characteristics of a Southeast Asian strain (NIID123) and an American strain (PRVABC59) revealed that the latter had a higher replication ability in cultured cells and higher virulence in mice. In this study, we aimed to identify the genetic region of ZIKV responsible for these different characteristics using reverse genetics. A chimeric NIID123 strain in which the E protein was replaced with that of PRVABC59 showed a lower growth ability than the recombinant wild-type strain. Adaptation of the chimeric NIID123 to Vero cells induced a Phe-to-Leu amino acid substitution at position 146 of the prM protein; PRVABC59 also has Leu at this position. Leu at this position was found to be responsible for the viral replication ability and partially, for the pathogenicity in mouse testes.

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Combined proteome and transcriptome analyses reveal that Zika virus circulating in Brazil alters cell cycle and neurogenic programmes in human neurospheres

10.7287/peerj.preprints.2033 ◽

2016 ◽

Cited By ~ 1

Author(s):

Patricia P Garcez ◽

Juliana Minardi Nascimento ◽

Janaina Mota de Vasconcelos ◽

Rodrigo Madeiro da Costa ◽

Rodrigo Delvecchio ◽

...

Keyword(s):

Cell Cycle ◽

Stem Cells ◽

Cell Death ◽

Zika Virus ◽

Congenital Infection ◽

Protein Translation ◽

Biological Mechanisms ◽

Induce Cell Death ◽

Human Brain Development ◽

Brain Malformations

Zika virus (ZIKV) has been associated with microcephaly and other brain abnormalities; however, the molecular and cellular consequences of Zika virus circulating in Brazil to the human brain development have not been studied yet. Here we describe alterations in human neurospheres derived from neural stem cells infected with Brazilian ZIKV. Combined proteomics and mRNA transcriptional profile analyses showed that Brazilian ZIKV, prior to induce cell death, alters cell cycle and halts neurogenic programmes, in addition to regulate transcription and protein translation due to viral replication. These results point to biological mechanisms potentially implicated in brain malformations as a result of ZIKV congenital infection.

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Immune Profile of the Normal Maternal-Fetal Interface in Rhesus Macaques and Its Alteration Following Zika Virus Infection

Frontiers in Immunology ◽

10.3389/fimmu.2021.719810 ◽

2021 ◽

Vol 12 ◽

Author(s):

Matilda J. Moström ◽

Elizabeth A. Scheef ◽

Lesli M. Sprehe ◽

Dawn Szeltner ◽

Dollnovan Tran ◽

...

Keyword(s):

T Lymphocytes ◽

Nk Cells ◽

B Lymphocytes ◽

Vertical Transmission ◽

Zika Virus ◽

Peripheral Blood ◽

Congenital Infection ◽

Effector Memory ◽

Cd8 T Lymphocytes ◽

Maternal Fetal Interface

The maternal decidua is an immunologically complex environment that balances maintenance of immune tolerance to fetal paternal antigens with protection of the fetus against vertical transmission of maternal pathogens. To better understand host immune determinants of congenital infection at the maternal-fetal tissue interface, we performed a comparative analysis of innate and adaptive immune cell subsets in the peripheral blood and decidua of healthy rhesus macaque pregnancies across all trimesters of gestation and determined changes after Zika virus (ZIKV) infection. Using one 28-color and one 18-color polychromatic flow cytometry panel we simultaneously analyzed the frequency, phenotype, activation status and trafficking properties of αβ T, γδ T, iNKT, regulatory T (Treg), NK cells, B lymphocytes, monocytes, macrophages, and dendritic cells (DC). Decidual leukocytes showed a striking enrichment of activated effector memory and tissue-resident memory CD4+ and CD8+ T lymphocytes, CD4+ Tregs, CD56+ NK cells, CD14+CD16+ monocytes, CD206+ tissue-resident macrophages, and a paucity of B lymphocytes when compared to peripheral blood. t-distributed stochastic neighbor embedding (tSNE) revealed unique populations of decidual NK, T, DC and monocyte/macrophage subsets. Principal component analysis showed distinct spatial localization of decidual and circulating leukocytes contributed by NK and CD8+ T lymphocytes, and separation of decidua based on gestational age contributed by memory CD4+ and CD8+ T lymphocytes. Decidua from 10 ZIKV-infected dams obtained 16-56 days post infection at third (n=9) or second (n=1) trimester showed a significant reduction in frequency of activated, CXCR3+, and/or Granzyme B+ memory CD4+ and CD8+ T lymphocytes and γδ T compared to normal decidua. These data suggest that ZIKV induces local immunosuppression with reduced immune recruitment and impaired cytotoxicity. Our study adds to the immune characterization of the maternal-fetal interface in a translational nonhuman primate model of congenital infection and provides novel insight in to putative mechanisms of vertical transmission.

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