Cytomegalovirus Initiates Infection Selectively from High-Level β1 Integrin–Expressing Cells in the Brain

Kawasaki, Hideya; Kosugi, Isao; Sakao-Suzuki, Makiko; Meguro, Shiori; Arai, Yoshifumi; Tsutsui, Yoshihiro; Iwashita, Toshihide

doi:10.1016/j.ajpath.2015.01.032

Cited by 22 publications

(23 citation statements)

References 66 publications

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“…We previously evaluated the differences in intraventricular and intravascular infection mouse models to investigate the relationship between distributions of MCMV particles and receptors in the neonatal mouse brain during the first viremic phase . Development in the neonatal mouse CNS is comparable to that in human fetuses at 17–20 weeks of gestation, and congenital HCMV infection is most often acquired during the early second trimester .…”

Section: Mcmv‐induced Brain Defects Are Caused By Disturbances In Neumentioning

confidence: 99%

“…h) at 12 hpi. CD31‐ cells and PDGFRβ‐positive cells express high levels of β1 integrin, which can trap MCMV particles during initial infection. A previous report confirmed that inhibition of β1 integrin by short hairpin RNA and functional blocking antibody significantly reduced MCMV infection.…”

Section: Mcmv‐induced Brain Defects Are Caused By Disturbances In Neumentioning

confidence: 99%

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Pathogenesis of developmental anomalies of the central nervous system induced by congenital cytomegalovirus infection

Kawasaki

Kosugi

Meguro

et al. 2017

Pathology International

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In humans, the herpes virus family member cytomegalovirus (CMV) is the most prevalent mediator of intrauterine infection-induced congenital defect. Central nervous system (CNS) dysfunction is a distinguishing symptom of CMV infection, and characterized by ventriculoencephalitis and microglial nodular encephalitis. Reports on the initial distribution of CMV particles and its receptors on the blood brain barrier (BBB) are rare. Nevertheless, several factors are suggested to affect CMV etiology. Viral particle size is the primary factor in determining the pattern of CNS infections, followed by the expression of integrin β1 in endothelial cells, pericytes, meninges, choroid plexus, and neural stem progenitor cells (NSPCs), which are the primary targets of CMV infection. After initial infection, CMV disrupts BBB structural integrity to facilitate the spread of viral particles into parenchyma. Then, the initial meningitis and vasculitis eventually reaches NSPC-dense areas such as ventricular zone and subventricular zone, where viral infection inhibits NSPC proliferation and differentiation and results in neuronal cell loss. These cellular events clinically manifest as brain malformations such as a microcephaly. The purpose of this review is to clearly delineate the pathophysiological basis of congenital CNS anomalies caused by CMV.

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Section: Mcmv‐induced Brain Defects Are Caused By Disturbances In Neumentioning

confidence: 99%

Section: Mcmv‐induced Brain Defects Are Caused By Disturbances In Neumentioning

confidence: 99%

Pathogenesis of developmental anomalies of the central nervous system induced by congenital cytomegalovirus infection

Kawasaki

Kosugi

Meguro

et al. 2017

Pathology International

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“…CMV neuroinvasiveness is mediated by a variety of entry factors, including integrins and EGFR, which are highly expressed by radial glia. Higher expression of these entry proteins determines the initial susceptible cell population (Kawasaki et al, 2015). …”

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confidence: 99%

Expression Analysis Highlights AXL as a Candidate Zika Virus Entry Receptor in Neural Stem Cells

et al. 2016

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Summary The recent outbreak of Zika virus (ZIKV) in Brazil has been linked to substantial increases in fetal abnormalities and microcephaly. However, information about the underlying molecular and cellular mechanisms connecting viral infection to these defects remains limited. In this study we have examined the expression of receptors implicated in cell entry of several enveloped viruses including ZIKV across diverse cell types in the developing brain. Using single cell RNA-Seq and immunohistochemistry, we found that the candidate viral entry receptor AXL is highly expressed by human radial glial cells, astrocytes, endothelial cells, and microglia in developing human cortex, and by progenitor cells in developing retina. We also show that AXL expression in radial glia is conserved in developing mouse and ferret cortex, and in human stem cell-derived cerebral organoids, highlighting multiple experimental systems that could be applied to study mechanisms of ZIKV infectivity and effects on brain development.

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“…Although unrelated to ZIKV, infection with CMV causes similar neurodevelopmental brain abnormalities [67,120]. The neuroinvasiveness of CMV is mediated by various entry factors, such as EGFR and integrins, which are particularly highly expressed in radial glia and neural stem/progenitor cells [121]. Higher expression of these entry proteins, particularly of β1 integrin in this case, determines the initial susceptible cell population in the brain.…”

Section: Vertical Transmission: Crossing the Placental Barriermentioning

confidence: 99%

The journey of Zika to the developing brain

et al. 2020

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Zika virus is a mosquito-borne Flavivirus originally isolated from humans in 1952. Following its re-emergence in Brazil in 2015, an increase in the number of babies born with microcephaly to infected mothers was observed. Microcephaly is a neurodevelopmental disorder, characterised phenotypically by a smaller than average head size, and is usually developed in utero. The 2015 outbreak in the Americas led to the World Health Organisation declaring Zika a Public Health Emergency of International Concern. Since then, much research into the effects of Zika has been carried out. Studies have investigated the structure of the virus, its effects on and evasion of the immune response, cellular entry including target receptors, its transmission from infected mother to foetus and its cellular targets. This review discusses current knowledge and novel research into these areas, in hope of developing a further understanding of how exposure of pregnant women to the Zika virus can lead to impaired brain development of their foetus. Although no longer considered an epidemic in the Americas, the mechanism by which Zika acts is still not comprehensively and wholly understood, and this understanding will be crucial in developing effective vaccines and treatments.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Cytomegalovirus Initiates Infection Selectively from High-Level β1 Integrin–Expressing Cells in the Brain

Cited by 22 publications

References 66 publications

Pathogenesis of developmental anomalies of the central nervous system induced by congenital cytomegalovirus infection

Pathogenesis of developmental anomalies of the central nervous system induced by congenital cytomegalovirus infection

Expression Analysis Highlights AXL as a Candidate Zika Virus Entry Receptor in Neural Stem Cells

The journey of Zika to the developing brain

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