Role of microglia in the dissemination of Zika virus from mother to fetal brain

Xu, Pei; Shan, Chao; Dunn, Tiffany J.; Xie, Xuping; Xia, Hongjie; Gao, Junling; Labastida, Javier Allende; Zou, Jing; Villarreal, Paula; Schlagal, Caitlin R.; Yu, Yongjia; Vargas, Gracie; Rossi, Shannan L.; Vasilakis, Nikolaos; Shi, Pei Yong; Weaver, Scott C.; Wu, Ping

doi:10.1371/journal.pntd.0008413

Cited by 28 publications

(21 citation statements)

References 72 publications

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“…It was shown that an acute ablation of CSF1R resulting in a depletion of microglia results in a decreased viral load in the brain, supporting a "Trojan horse" model of ZIKV infection (142) (Figure 2). In vivo and in vitro data underlined that murine microglia progenitor cells from the yolk sac are indeed susceptible to ZIKV infection (142). In vitro data showed that infected human induced pluripotent stem cell (iPSC)-derived microglia-like cells co-cultured with neural spheroids leads to propagation of the virus to the neural tissue which supports the claim that microglia act as a viral reservoir for ZIKV and push ahead neural infection in the fetal brain (140).…”

Section: Zika Virus (Zikv)mentioning

confidence: 77%

“…Indeed, it was shown that the virus targets neuronal progenitor cells (NPCs), astrocytes and microglia, while only being cytotoxic in NPCs and causing their growth arrest and apoptosis ( 140 , 141 ). Especially microglia are among the main suspects to disseminate ZIKV in the brain as the particular susceptibility between E6.5-E8.5 in mice coincides with a critical window of microglia development and the beginning of their migration via the newly formed blood circulation toward the brain ( 142 ). It was shown that an acute ablation of CSF1R resulting in a depletion of microglia results in a decreased viral load in the brain, supporting a “Trojan horse” model of ZIKV infection ( 142 ) ( Figure 2 ).…”

Section: Fetal Infectionsmentioning

confidence: 99%

“…Especially microglia are among the main suspects to disseminate ZIKV in the brain as the particular susceptibility between E6.5-E8.5 in mice coincides with a critical window of microglia development and the beginning of their migration via the newly formed blood circulation toward the brain ( 142 ). It was shown that an acute ablation of CSF1R resulting in a depletion of microglia results in a decreased viral load in the brain, supporting a “Trojan horse” model of ZIKV infection ( 142 ) ( Figure 2 ). In vivo and in vitro data underlined that murine microglia progenitor cells from the yolk sac are indeed susceptible to ZIKV infection ( 142 ).…”

Section: Fetal Infectionsmentioning

confidence: 99%

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CNS Macrophages and Infant Infections

et al. 2020

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The central nervous system (CNS) harbors its own immune system composed of microglia in the parenchyma and CNS-associated macrophages (CAMs) in the perivascular space, leptomeninges, dura mater, and choroid plexus. Recent advances in understanding the CNS resident immune cells gave new insights into development, maturation and function of its immune guard. Microglia and CAMs undergo essential steps of differentiation and maturation triggered by environmental factors as well as intrinsic transcriptional programs throughout embryonic and postnatal development. These shaping steps allow the macrophages to adapt to their specific physiological function as first line of defense of the CNS and its interfaces. During infancy, the CNS might be targeted by a plethora of different pathogens which can cause severe tissue damage with potentially long reaching defects. Therefore, an efficient immune response of infant CNS macrophages is required even at these early stages to clear the infections but may also lead to detrimental consequences for the developing CNS. Here, we highlight the recent knowledge of the infant CNS immune system during embryonic and postnatal infections and the consequences for the developing CNS.

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Section: Zika Virus (Zikv)mentioning

confidence: 77%

Section: Fetal Infectionsmentioning

confidence: 99%

Section: Fetal Infectionsmentioning

confidence: 99%

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CNS Macrophages and Infant Infections

et al. 2020

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“…Several neurotropic viruses have been shown to induce microglia activation in the CNS following infection, including Japanese encephalitis virus [ 43 , 44 ], Dengue Virus [ 45 ], Zika virus [ 46 ], Tick-borne encephalitis virus [ 47 ], reovirus [ 48 ], and mouse hepatitis virus [ 49 , 50 ]. Evidence that microglia are activated during WNV-induced CNS disease in humans includes the presence of microglial nodules and increased proliferation [ 51 , 52 ].…”

Section: Microglia Become Activated During Wnv Infectionmentioning

confidence: 99%

The Role of Microglia during West Nile Virus Infection of the Central Nervous System

2020

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Encephalitis resulting from viral infections is a major cause of hospitalization and death worldwide. West Nile Virus (WNV) is a substantial health concern as it is one of the leading causes of viral encephalitis in the United States today. WNV infiltrates the central nervous system (CNS), where it directly infects neurons and induces neuronal cell death, in part, via activation of caspase 3-mediated apoptosis. WNV infection also induces neuroinflammation characterized by activation of innate immune cells, including microglia and astrocytes, production of inflammatory cytokines, breakdown of the blood-brain barrier, and infiltration of peripheral leukocytes. Microglia are the resident immune cells of the brain and monitor the CNS for signs of injury or pathogens. Following infection with WNV, microglia exhibit a change in morphology consistent with activation and are associated with increased expression of proinflammatory cytokines. Recent research has focused on deciphering the role of microglia during WNV encephalitis. Microglia play a protective role during infections by limiting viral growth and reducing mortality in mice. However, it also appears that activated microglia are triggered by T cells to mediate synaptic elimination at late times during infection, which may contribute to long-term neurological deficits following a neuroinvasive WNV infection. This review will discuss the important role of microglia in the pathogenesis of a neuroinvasive WNV infection. Knowledge of the precise role of microglia during a WNV infection may lead to a greater ability to treat and manage WNV encephalitis.

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“…Moreover, they may play a role in ZIKV transmission from mother to fetal brain [17] and affect the proliferation and differentiation of neuronal progenitor cells [18]. In order to comprehend the molecular bases behind the efficacy of the IFN response to ZIKV replication, we set up a high throughput assay to identify genes that are modulating viral replication in human microglial cells (HMC3) stimulated with IFN.…”

Section: Introductionmentioning

confidence: 99%

Discovery of genes that modulate flavivirus replication in an interferon-dependent manner

Lesage

Chazal

Beauclair

et al. 2021

Preprint

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Establishment of the interferon (IFN)-mediated antiviral state provides a crucial initial line of defense against viral infection. Numerous genes that contribute to this antiviral state remain to be identified. Using a loss-of-function strategy, we screened an original library of 1156 siRNAs targeting 386 individual curated human genes in stimulated microglial cells infected with Zika virus (ZIKV), an emerging RNA virus that belongs to the flavivirus genus. The screen recovered twenty-one potential host proteins that modulate ZIKV replication in an IFN-dependent manner, including the previously known IFITM3 and LY6E. Further characterization contributed to delineate the spectrum of action of these genes towards other pathogenic RNA viruses, including Hepatitis C virus and SARS-CoV-2. Our data revealed that APOL3 acts as a proviral factor for ZIKV and several other related and unrelated RNA viruses. In addition, we showed that MTA2, a chromatin remodeling factor, possesses potent flavivirus-specific antiviral functions. Our work identified previously unrecognized genes that modulate the replication of RNA viruses in an IFN-dependent way, opening new perspectives to target weakness points in the life cycle of these viruses.

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Role of microglia in the dissemination of Zika virus from mother to fetal brain

Cited by 28 publications

References 72 publications

CNS Macrophages and Infant Infections

CNS Macrophages and Infant Infections

The Role of Microglia during West Nile Virus Infection of the Central Nervous System

Discovery of genes that modulate flavivirus replication in an interferon-dependent manner

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