Zika virus infects pericytes in the choroid plexus and enters the central nervous system through the blood-cerebrospinal fluid barrier

Kim, Jihye; Alejandro, Brian; Hetman, Michał; Hattab, Eyas M.; Joiner, Joshua; Schroten, Horst; Ishikawa, Hiroshi; Chung, Donghoon

doi:10.1371/journal.ppat.1008204

Cited by 48 publications

(46 citation statements)

References 75 publications

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“… 52 Interestingly, the latest research on a murine model of ZIKV infection suggests that the ZIKV may invade the CNS by crossing the blood-CSF barrier rather than the BBB by infecting pericytes in the choroid plexus. 53 This puts forward new opportunities for us to study the mechanism of flavivirus invasion of the CNS.…”

Section: Pericytes Of the Bbbmentioning

confidence: 99%

Immune response and blood–brain barrier dysfunction during viral neuroinvasion

Chen

2020

Innate Immun

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The blood-brain barrier (BBB), which protects the CNS from pathogens, is composed of specialized brain microvascular endothelial cells (BMECs) joined by tight junctions and ensheathed by pericytes and astrocyte endfeet. The stability of the BBB structure and function is of great significance for the maintenance of brain homeostasis. When a neurotropic virus invades the CNS via a hematogenous or non-hematogenous route, it may cause structural and functional disorders of the BBB, and also activate the BBB anti-inflammatory or pro-inflammatory innate immune response. This article focuses on the structural and functional changes that occur in the three main components of the BBB (endothelial cells, astrocytes, and pericytes) in response to infection with neurotropic viruses transmitted by hematogenous routes, and also briefly describes the supportive effect of three cells on the BBB under normal physiological conditions. For example, all three types of cells express several PRRs, which can quickly sense the virus and make corresponding immune responses. The pro-inflammatory immune response will exacerbate the destruction of the BBB, while the anti-inflammatory immune response, based on type I IFN, consolidates the stability of the BBB. Exploring the details of the interaction between the host and the pathogen at the BBB during neurotropic virus infection will help to propose new treatments for viral encephalitis. Enhancing the defense function of the BBB, maintaining the integrity of the BBB, and suppressing the pro-inflammatory immune response of the BBB provide more ideas for limiting the neuroinvasion of neurotropic viruses. In the future, these new treatments are expected to cooperate with traditional antiviral methods to improve the therapeutic effect of viral encephalitis.

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Section: Pericytes Of the Bbbmentioning

confidence: 99%

Immune response and blood–brain barrier dysfunction during viral neuroinvasion

Chen

2020

Innate Immun

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“…Alternatively, pericytes could also take a role during the CNS entry of SARS-CoV-2 in a similar manner shown for another neurotropic virus recently. 61 The key role of the angiotensin system in cephalic nociception and the migraine has also been implicated previously. 3,62,63 The expression of Ang II in the neurons of human and rat trigeminal system infers its function in the regulation of cephalic nociception.…”

Section: -The Diagram Summarizing the Hypothetical Mechanisms Of The mentioning

confidence: 85%

Are Migraine Patients at Increased Risk for Symptomatic Coronavirus Disease 2019 Due to Shared Comorbidities?

et al. 2020

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The coronavirus disease 2019 (COVID-19) pandemic has rapidly transformed the whole world and forced us to look through comorbid diseases and risk factors from a different perspective. COVID-19 shows some inherent risk factors like cardiovascular comorbidities independent from age, gender, and geographic location. One of the most peculiar features of the COVID-19 pandemic is that severe acute respiratory syndrome coronavirus 2 respiratory infections disproportionately impact patients with hypertension, diabetes, and other cardiovascular comorbidities rather than those with allergic respiratory diseases and immunecompromised conditions. Migraine is a complex neuro-vasculo-inflammatory disorder that is also packed frequently with certain medical conditions including vascular disorders, hypertension, allergic diseases such as asthma and systemic inflammatory disorders. Accordingly, 2 different questions arise during the pandemic: (1) Do share comorbidities of cardiovascular diseases and hypertension increase the risk of symptomatic COVID-19 for migraine patients? (2) Do comorbid allergic and atopic diseases, including asthma act as opposite influencers alongside with female gender? This paper focuses on the coexistence of comorbidities of COVID-19, in comparison with migraine, based on a wide clinical dataset and available reports. Discussed mechanisms include potential strategic roles of angiotensin-converting enzyme 2, angiotensin-II, and nucleotide oligomerization domain-like receptor family, pyrin domain containing 3 inflammasome, playing remarkable parts in the pathogenesis of COVID-19 and migraine. There are also some clues about the importance of endothelial and pericyte dysfunction and neuroinflammation in COVID-19 infection, related to complications and survival of the patients. The large epidemiological studies as well as basic research, focusing on migraine patients with COVID-19 will clarify these vital questions during the upcoming periods.

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“…ChP acts as a barrier separating the blood from the CSF (Lun et al, 2015;Javed et al, 2020). This barrier is also a site of virus entry and spread into CNS, as demonstrated by the infection of ChP's pericytes with ZIKV that invades the CNS (Kim et al, 2020). The ChP epithelial cells infected with human polyomavirus (JCPyV) produce extracellular vesicles that spreads towards glial cells (O'Hara et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Non-permissive SARS-CoV-2 infection in human neurospheres

Pedrosa

Goto‐Silva

Temerozo

et al. 2020

Preprint

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Coronavirus disease 2019 (COVID-19) was initially described as a viral infection of the respiratory tract. It is now known, however, that many other biological systems are affected, including the central nervous system (CNS). Neurological manifestations such as stroke, encephalitis, and psychiatric conditions have been reported in COVID-19 patients, but its neurotropic potential is still debated. Here, we investigate the presence of SARS-CoV-2 in the brain from an infant patient deceased from COVID-19. The susceptibility to virus infection was compatible with the expression levels of viral receptor ACE2, which is increased in the ChP in comparison to other brain areas. To better comprehend the dynamics of the viral infection in neural cells, we exposed human neurospheres to SARS-CoV-2. Similarly to the human tissue, we found viral RNA in neurospheres, although viral particles in the culture supernatant were not infective. Based on our observations in vivo and in vitro, we hypothesize that SARS-CoV-2 does not generate productive infection in developing neural cells and that infection of ChP weakens the blood-cerebrospinal fluid barrier allowing viruses, immune cells, and cytokines to access the CNS, causing neural damage in the young brain.

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Zika virus infects pericytes in the choroid plexus and enters the central nervous system through the blood-cerebrospinal fluid barrier

Cited by 48 publications

References 75 publications

Immune response and blood–brain barrier dysfunction during viral neuroinvasion

Immune response and blood–brain barrier dysfunction during viral neuroinvasion

Are Migraine Patients at Increased Risk for Symptomatic Coronavirus Disease 2019 Due to Shared Comorbidities?

Non-permissive SARS-CoV-2 infection in human neurospheres

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