Zika virus crosses an in vitro human blood brain barrier model

Alimonti, Judie B.; Ribecco-Lutkiewicz, Maria; Sodja, Caroline; Jezierski, Anna; Stanimirovic, Danica; Liu, Qing; Haqqani, Arsalan S.; Conlan, Wayne; Bani‐Yaghoub, Mahmud

doi:10.1186/s12987-018-0100-y

Cited by 65 publications

(57 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the current study, the ZIKV can cross brain endothelial cells and release of infectious virus particles, without an increase of endothelial monolayer permeability and no significant cytotoxicity in vitro (Figures 1, 2, 7). This is in agreement with previous studies showing the ZIKV crosses the BBB monolayer without the BBB barrier disruption (Papa et al, 2017;Alimonti et al, 2018). However, our studies showed that there were infectious atto647N-labeled virus particles that crossed the monolayer of BBB barrier cells in the presence of the treatment of endocytic inhibitors (Figures 7C,D), suggesting that we still cannot exclude the possibility that some viral particles selectively modulate tight junctions and cross the bottom chamber via paracellular diapedesis without overtly disrupting the BBB permeability.…”

Section: Discussionsupporting

confidence: 93%

“…Disruption of the BBB enhances permeability of endothelial cell and is a hallmark of CNS infection (Daniels and Klein, 2015). However, recent studies reported that no barrier disruption was observed when ZIKV gained access to the CNS (Papa et al, 2017;Alimonti et al, 2018), suggesting that the endocytic transport system is required for the ZIKV to cross the BBB barrier. Given the existence of endosomal sorting pathways in different cell types, it is possible for the BBB cells to employ a similar process of endosomal transportation (Ayloo and Gu, 2019).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Mechanism of the Zika Virus Crossing the Placental Barrier and the Blood-Brain Barrier

Chiu¹,

Chu²,

Liao³

et al. 2020

Front. Microbiol.

View full text Add to dashboard Cite

Zika virus (ZIKV) infection causes severe neurological symptoms in adults and fetal microcephaly and the virus is detected in the brain of microcephaly and meningoencephalitis patient. However, the mechanism of ZIKV crossing the physiological barrier to the central nervous systems (CNS) remains elusive. The placental barrier and the blood brain barrier (BBB) protect the fetus from pathogens and ensure healthy brain development during pregnancy. In this study, we used human placenta trophoblasts cells (JEG-3) and human brain-derived endothelial cells (hCMEC/D3) as in vitro models of the physiological barriers. Results showed that ZIKV could infect JEG-3 cells effectively and reduce the amounts of ZO-1 and occludin between adjacent cells by the proteasomal degradation pathway, suggesting that the permeability of the barrier differentially changed in response to ZIKV infection, allowing the virus particle to cross the host barrier. In contrast, ZIKV could infect hCMEC/D3 cells without disrupting the BBB barrier permeability and tight junction protein expression. Although no disruption to the BBB was observed during ZIKV infection, ZIKV particles were released on the basal side of the BBB model and infected underlying cells. In addition, we observed that fluorescence-labeled ZIKV particles could cross the in vitro placenta barrier and BBB model by transcytosis and the action of transcytosis could be blocked by either low temperature or pharmacological inhibitors of endocytosis. In summary, the ZIKV uses a cell-type specific paracellular pathway to cross the placenta monolayer barrier by disrupting cellular tight junction. In addition, the ZIKV can also cross both the placenta barrier and the BBB by transcytosis. Our study provided new insights into on the mechanism of the cellular barrier penetration of ZIKV particles.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

The Mechanism of the Zika Virus Crossing the Placental Barrier and the Blood-Brain Barrier

Chiu¹,

Chu²,

Liao³

et al. 2020

Front. Microbiol.

View full text Add to dashboard Cite

show abstract

“…Surprisingly, barrier disruption in this model occurred independent of changes to tight junctions and rather by a previously unknown mechanism of impairment in cellmatrix interactions [52]. iBMECs have also been used for revealing how Zika virus crosses the BBB through paracellular diapedesis to infect the CNS without compromising BBB integrity [53]. These studies highlight that iBMECs can be used to elucidate how human-specific pathogens traverse the BBB to colonize the CNS and could guide the development of new therapeutics to combat infection.…”

Section: Infectious Diseasementioning

confidence: 88%

Recent advances in human iPSC-derived models of the blood–brain barrier

Workman

Svendsen

2020

Fluids Barriers CNS

View full text Add to dashboard Cite

The blood-brain barrier (BBB) is a critical component of the central nervous system that protects neurons and other cells of the brain parenchyma from potentially harmful substances found in peripheral circulation. Gaining a thorough understanding of the development and function of the human BBB has been hindered by a lack of relevant models given significant species differences and limited access to in vivo tissue. However, advances in induced pluripotent stem cell (iPSC) and organ-chip technologies now allow us to improve our knowledge of the human BBB in both health and disease. This review focuses on the recent progress in modeling the BBB in vitro using human iPSCs.

show abstract

“…These viruses can replicate in the CNS, cause encephalitis, and measurably affect BBB integrity (44–49). In contrast, results from an in vitro BBB reconstitution model using a primary virus isolate from Thailand, and an interferon receptor-deficient murine model using Ugandan and Brazilian isolates suggests that a primary isolate of ZIKV doesn’t significantly disrupt the BBB to gain access to the CNS and that long-term damage to the BBB is minimal (50, 51). Similarly, productive ZIKV infection of human MECs in vitro does not result in cytopathic effects (44).…”

Section: Discussionmentioning

confidence: 99%

A Zika Virus Primary Isolate Induces Neuroinflammation, Compromises the Blood-Brain Barrier, and Upregulates CXCL12 in Adult Macaques

Panganiban

Blair

Hattler

et al. 2019

Preprint

View full text Add to dashboard Cite

22Zika virus (ZIKV) is a neurotropic virus that can cause neuropathy in adults and fetal 23 neurologic malformation following infection of pregnant women. We used a nonhuman primate 24 model, the Indian-origin Rhesus macaque (IRM), to gain insight into virus-associated hallmarks 25 42 chemokine may be involved in virus-induced inflammation and/or in repair of virus-induced brain 43 damage. Our data are significant since they help in understanding the mechanism of brain 44 damage caused by ZIKV in adults. 45 3 46 Introduction 47 Zika virus (ZIKV), is a neurotropic flavivirus associated with Guillain-Barre' syndrome 48 (GBS) in adults and is also well-known for causing fetal neurologic malformation following 49 infection of pregnant women (1, 2). In addition to causing GBS, which features damage to the 50 protective myelin sheath surrounding axons, ZIKV can cause neuropathy in adults in the form of 51 meningioencephalitis and myelitis (3, 4). The pathogenesis of ZIKV and the host-pathogen 52 interactions important for the development of these lesions still need to be elucidated. 53The blood-brain barrier (BBB), the boundary between circulatory and CNS tissues, is 54 composed of brain microvascular endothelial cells (BMECs) and supporting associated pericytes 55 and astrocytes. Intercellular tight junction (TJ) and adherens junction (AJ) integrity is important 56 for maintenance of the intracellular network of MECs that comprises the vascular endothelium. 57 Disruption of the BBB occurs during the pathogenesis of a wide range of infectious, autoimmune, 58 and neurodegenerative diseases. Neurotropic flaviviruses, including Japanese Encephalitis virus 59 (JEV) and West Nile virus (WNV), disturb the BBB in adults through disruption of the BMEC 60 network (5, 6). 61The chemokine CXCL12 is a key regulator of both myelin formation during embryogenesis 62 and remyelination following neural damage in the CNS and peripheral nervous system (PNS) in 63 adults (7, 8). CXCL12 facilitates the migration and maturation of oligodendrocyte precursor cells 64 (OPCs) during CNS remyelination (7, 8). In the PNS, CXCL12 may similarly function in Schwann 65 cell migration (9), as CXCL12 is expressed by perisynaptic Schwann cells during recovery of 66 neuromuscular junctions following damage (10). In addition to serving as a key regulator of neural 67 repair, CXCL12 plays an important function in regulating lymphocyte migration through the BBB. 68During homeostasis CXCL12 is expressed by BMECs resulting in spatial restriction of 69 lymphocytes to the microvascular perivascular space, and changes in chemokine expression and 70 distribution can lead to neuroinflammation (11, 12). The role of CXCL12 in neural repair, 4 71 lymphocyte migration into the CNS parenchyma, and in multifarious functions during development 72 and immunity, are mediated through interaction of this chemokine with its primary receptor, 73 CXCR4 (13). Stimulation of CXCR4 by CXCL12 results in activation of an interwoven set of 74 downstream effector pathways (14, 15)....

show abstract

Zika virus crosses an in vitro human blood brain barrier model

Cited by 65 publications

References 40 publications

The Mechanism of the Zika Virus Crossing the Placental Barrier and the Blood-Brain Barrier

The Mechanism of the Zika Virus Crossing the Placental Barrier and the Blood-Brain Barrier

Recent advances in human iPSC-derived models of the blood–brain barrier

A Zika Virus Primary Isolate Induces Neuroinflammation, Compromises the Blood-Brain Barrier, and Upregulates CXCL12 in Adult Macaques

Contact Info

Product

Resources

About