TORCH Infections

Neu, Natalie; Duchon, Jennifer; Zachariah, Philip

doi:10.1016/j.clp.2014.11.001

Cited by 252 publications

(200 citation statements)

References 62 publications

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“…These models mimic the first trimester of brain development, indicating that ZIKV infection during this developmental time window may result in severe damage. Other studies are necessary to further characterize the consequences of ZIKV infection during different stages of fetal development.Cell death that impairs brain enlargement, calcification, and microcephaly are well described in congenital infections with TORCHS factors (3, 23,24). Our results, together with recent studies showing brain calcification in microcephalic fetuses and newborns infected with ZIKV (10, 14), reinforce the growing body of evidence connecting the ZIKV outbreak to the increased reports of congenital brain malformations in Brazil.…”

supporting

confidence: 77%

Zika virus impairs growth in human neurospheres and brain organoids

Garcez

Loiola

Costa

et al. 2016

Science

1,036

618

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Since the emergence of Zika virus (ZIKV), reports of microcephaly have increased considerably in Brazil; however, causality between the viral epidemic and malformations in fetal brains needs further confirmation. We examined the effects of ZIKV infection in human neural stem cells growing as neurospheres and brain organoids. Using immunocytochemistry and electron microscopy, we showed that ZIKV targets human brain cells, reducing their viability and growth as neurospheres and brain organoids. These results suggest that ZIKV abrogates neurogenesis during human brain development. P rimary microcephaly is a severe brain malformation characterized by the reduction of the head circumference. Patients display a heterogeneous range of brain impairments that compromise motor, visual, hearing, and cognitive functions (1).Microcephaly is associated with decreased neuronal production as a consequence of proliferative defects and death of cortical progenitor cells (2). During pregnancy, the primary etiology of microcephaly varies from genetic mutations to external insults. The so-called TORCHS factors (toxoplasmosis, rubella, cytomegalovirus, herpes virus, and syphilis) are the main congenital infections that compromise brain development in utero (3).An increase in the rate of microcephaly in Brazil has been associated with the recent outbreak of Zika virus (ZIKV) (4, 5), a flavivirus that is transmitted by mosquitoes (6) and sexually (7-9). So far, ZIKV has been described in the placenta and amniotic fluid of microcephalic fetuses (10-13) and in the blood of microcephalic newborns (11, 14). ZIKV had also been detected within the brain of a microcephalic fetus (13, 14), and recently, direct evidence has emerged that ZIKV is able to infect and cause the death of neural stem cells (15).We used human induced pluripotent stem (iPS) cells cultured as neural stem cells (NSCs), neurospheres, and brain organoids to explore the consequences of ZIKV infection during neurogenesis and growth with three-dimensional culture models. Human iPS-derived NSCs were exposed to ZIKV [multiplicity of infection (MOI), 0.25 to 0.0025]. After 24 hours, ZIKV was detected in NSCs (Fig. 1, A to D); viral envelope protein was evident in 10.10% (MOI, 0.025) and 21.7% (MOI, 0.25) of cells exposed to ZIKV (Fig. 1E). Viral RNA was also detected in the supernatant of infected NSCs (MOI, 0.0025) by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) ( Fig. 1F), providing evidence of productive infection.To investigate the effects of ZIKV during neural differentiation, mock-and ZIKV-infected NSCs were cultured as neurospheres. After 3 days in vitro (DIV), mock-infected NSCs generated round neurospheres. However, ZIKVinfected NSCs generated neurospheres with morphological abnormalities and cell detachment ( Mock-infected neurospheres presented the expected ultrastructural morphology of the nucleus and mitochondria (Fig. 3A). Viral particles were present in ZIKV-infected neurospheres, similar to those observed in murine glial and neuronal cel...

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supporting

confidence: 77%

Zika virus impairs growth in human neurospheres and brain organoids

Garcez

Loiola

Costa

et al. 2016

Science

1,036

618

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“…A large proportion of microcephaly cases remain unexplained as they have not been linked to any genetic origin. Possible explanations for some of these cases may include exposure to certain infections during pregnancy, the so called TORCHS factors, such as toxoplasmosis, rubella, cytomegalovirus, herpes virus, and syphilis; as well as severe malnutrition, exposure to harmful substances, such as alcohol, certain drugs, toxic chemicals or interruption of the blood supply during development [300,301]. Zika virus (ZIKV) carried by mosquitos, now joins the list of viral TORCH pathogens [302].…”

Section: Non-genetic Origins Of Mcds (Illustrated By Zika Virus Infecmentioning

confidence: 99%

Genetics and mechanisms leading to human cortical malformations

Romero

Bahi‐Buisson

Francis

2018

Seminars in Cell & Developmental Biology

100

109

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“…influenza, malaria, hepatitis E, measles, herpes simplex virus) and the risk of congenital anomalies for the foetuses (e.g. the "TORCH" pathogens: Toxoplasma gondii, other [syphilis, varicellazoster virus, parvovirus B19], rubella virus, cytomegalovirus and herpes simplex virus) [1,11]. These changes include modifications to the immune system driven by hormones, cytokines and immune cells as well as structural changes such as remodelling of the endometrium [1,12].…”

Section: The Immune System During Pregnancy and The Effect Of Maternamentioning

confidence: 99%

Maternal immunization: where are we now and how to move forward?

et al. 2018

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Pregnancy and the postpartum period are associated with elevated risks to both mother and infant from infectious disease. Vaccination of pregnant women, also called maternal immunization, has the potential to protect pregnant women, foetuses and infants from several vaccinepreventable diseases. Maternal immunoglobulin G antibodies are actively transferred through the placenta to provide passive immunity to new-borns during the first months of life, until the time for infant vaccinations or until the period of greatest susceptibility has passed. Currently, inactivated influenza, tetanus, and pertussis vaccines are recommended during pregnancy in many countries, but other vaccines may also be administered to pregnant women when risk factors are present. Several new vaccines with a specific indication for use during pregnancy are under development (e.g. respiratory syncytial virus and group B streptococcus vaccines). Years of experience suggest that maternal immunization against influenza, tetanus or pertussis has an acceptable safety profile, is well tolerated, effective and confers significant benefits to pregnant women and their infants. This review describes the principles of maternal immunization and provides an update of the recent evidence regarding the use and timing of maternal immunization. Finally, the barriers preventing wider vaccination coverage and the current limitations in addressing these are also described (Supplementary Material). KEY MESSAGESMaternal immunization gives pregnant women greater protection against infectious diseases; induces high levels of maternal antibodies that can be transferred to the foetus; and helps protect new-borns during their first months of life, until they are old enough to be vaccinated. Pregnant women and new-borns are more vulnerable to infectious diseases than the overall population; nevertheless, vaccination rates are often low in pregnant women. This review provides an update of the recent evidence regarding the use and timing of maternal immunization and describes the barriers preventing wider vaccination uptake and the current limitations in addressing these. ARTICLE HISTORY

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TORCH Infections

Cited by 252 publications

References 62 publications

Zika virus impairs growth in human neurospheres and brain organoids

Zika virus impairs growth in human neurospheres and brain organoids

Genetics and mechanisms leading to human cortical malformations

Maternal immunization: where are we now and how to move forward?

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