Pathophysiology and Mechanisms of Zika Virus Infection in the Nervous System

Christian, Kimberly M.; Song, Hongjun; Ming, Guo‐li

doi:10.1146/annurev-neuro-080317-062231

Cited by 49 publications

(34 citation statements)

References 126 publications

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“…It is now clear that chronic HIV infection correlates with dementia and other neurocognitive disorders ( Naghavi, 2018 ). Babies from ZIKV-infected mothers have microencephaly with consequences on their developmental and cognitive abilities into adulthood, while ZIKV causes neurodegenerative complications including myelitis, neuropathy and Guillain-Barre syndrome ( Christian et al, 2019 ). Of note, different quarters are beginning to sensitize the public about the possibility of post-COVID-19 pandemic of neurodegenerative diseases ( Serrano-Castro et al, 2020 ; Singal et al, 2020 ), given the neurological symptoms displayed during and after the infection (see section “Evidence of SARS-CoV-2 Neurotropism”).…”

Section: Perspectives: Implications Of Microglial Reactivity In Sars-cov-2 Related Neuropsychiatric Disorders and Neurodegenerative Diseamentioning

confidence: 99%

Microglial Implications in SARS-CoV-2 Infection and COVID-19: Lessons From Viral RNA Neurotropism and Possible Relevance to Parkinson’s Disease

Awogbindin

Ben-Azu

Olusola

et al. 2021

Front. Cell. Neurosci.

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Since December 2019, humankind has been experiencing a ravaging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, the second coronavirus pandemic in a decade after the Middle East respiratory syndrome coronavirus (MERS-CoV) disease in 2012. Infection with SARS-CoV-2 results in Coronavirus disease 2019 (COVID-19), which is responsible for over 3.1 million deaths worldwide. With the emergence of a second and a third wave of infection across the globe, and the rising record of multiple reinfections and relapses, SARS-CoV-2 infection shows no sign of abating. In addition, it is now evident that SARS-CoV-2 infection presents with neurological symptoms that include early hyposmia, ischemic stroke, meningitis, delirium and falls, even after viral clearance. This may suggest chronic or permanent changes to the neurons, glial cells, and/or brain vasculature in response to SARS-CoV-2 infection or COVID-19. Within the central nervous system (CNS), microglia act as the central housekeepers against altered homeostatic states, including during viral neurotropic infections. In this review, we highlight microglial responses to viral neuroinfections, especially those with a similar genetic composition and route of entry as SARS-CoV-2. As the primary sensor of viral infection in the CNS, we describe the pathogenic and neuroinvasive mechanisms of RNA viruses and SARS-CoV-2 vis-à-vis the microglial means of viral recognition. Responses of microglia which may culminate in viral clearance or immunopathology are also covered. Lastly, we further discuss the implication of SARS-CoV-2 CNS invasion on microglial plasticity and associated long-term neurodegeneration. As such, this review provides insight into some of the mechanisms by which microglia could contribute to the pathophysiology of post-COVID-19 neurological sequelae and disorders, including Parkinson’s disease, which could be pervasive in the coming years given the growing numbers of infected and re-infected individuals globally.

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Section: Perspectives: Implications Of Microglial Reactivity In Sars-cov-2 Related Neuropsychiatric Disorders and Neurodegenerative Diseamentioning

confidence: 99%

Microglial Implications in SARS-CoV-2 Infection and COVID-19: Lessons From Viral RNA Neurotropism and Possible Relevance to Parkinson’s Disease

Awogbindin

Ben-Azu

Olusola

et al. 2021

Front. Cell. Neurosci.

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“…The C protein and nonstructural proteins localize to various organelles in the neuron including nucleus and its nucleoli, Golgi apparatus, and lipid droplet in cytoplasm, causing cell cycle arrest, apoptosis, and cell death. 65,68 Nonstructural proteins NS4A and NS4B play a role in virus replication and assembly. 65 Zika virus has been demonstrated to cause host cell DNA damage by causing double-strand breaks and halt the host cell in its S phase, thus preventing its replication.…”

Section: Pathophysiology Of Zikv In Czsmentioning

confidence: 99%

A to Z of Zika Virus: A Comprehensive Review for Clinicians

Arora

2020

Global Pediatric Health

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Since its first outbreak in 2007 in the Pacific (Yap islands and Federal States of Micronesia), Zika virus has gradually and recently spread to the Americas in 2015. The neurotropic character of the virus was first noted during this outbreak in Brazil in 2015. Increasing number of infants born with microcephaly and other congenital deformities were identified through studies that have highlighted the importance of prevention of transmission of Zika virus in pregnant women. Long-term outcomes in infants born with this infection are now better understood than at the time of onset of this outbreak. Topics covered in this review include the history, modes of transmission, diagnosis of suspected cases, pathophysiology, complications, and prevention of Zika virus infection.

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“…Although infection of neural progenitors, neurons and glial cells have been described (Cugola et al, 2016;Gabriel et al, 2017;Büttner et al, 2019;Ferraris et al, 2019), a recent study based on in vitro research suggests that the primary targets of ZikV are astrocyte cells (Ledur et al, 2020). Such infection also affects cell migration, neurogenesis, differentiation and cell death, leading to microcephaly in neonates (Russo et al, 2017;Wen et al, 2017;Christian et al, 2019).…”

Section: Congenital Zika Virus Infectionmentioning

confidence: 99%

Implications of TORCH Diseases in Retinal Development—Special Focus on Congenital Toxoplasmosis

Campos

Calaza

Adesse

2020

Front. Cell. Infect. Microbiol.

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There are certain critical periods during pregnancy when the fetus is at high risk for exposure to teratogens. Some microorganisms, including Toxoplasma gondii, are known to exhibit teratogenic effects, interfering with fetal development and causing irreversible disturbances. T. gondii is an obligate intracellular parasite and the etiological agent of Toxoplasmosis, a zoonosis that affects one third of the world's population. Although congenital infection can cause severe fetal damage, the injury extension depends on the gestational period of infection, among other factors, like parasite genotype and host immunity. This parasite invades the Central Nervous System (CNS), forming tissue cysts, and can interfere with neurodevelopment, leading to frequent neurological abnormalities associated with T. gondii infection. Therefore, T. gondii is included in the TORCH complex of infectious diseases that may lead to neurological malformations (Toxoplasmosis, Others, Rubella, Cytomegalovirus, and Herpes). The retina is part of CNS, as it is derived from the diencephalon. Except for astrocytes and microglia, retinal cells originate from multipotent neural progenitors. After cell cycle exit, cells migrate to specific layers, undergo morphological and neurochemical differentiation, form synapses and establish their circuits. The retina is organized in nuclear layers intercalated by plexus, responsible for translating and preprocessing light stimuli and for sending this information to the brain visual nuclei for image perception. Ocular toxoplasmosis (OT) is a very debilitating condition and may present high severity in areas in which virulent strains are found. However, little is known about the effect of congenital infection on the biology of retinal progenitors/ immature cells and how this infection may affect the development of this tissue. In this context, this study reviews the effects that congenital infections may cause to the developing retina and the cellular and molecular aspects of these diseases, with special focus on congenital OT.

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Pathophysiology and Mechanisms of Zika Virus Infection in the Nervous System

Cited by 49 publications

References 126 publications

Microglial Implications in SARS-CoV-2 Infection and COVID-19: Lessons From Viral RNA Neurotropism and Possible Relevance to Parkinson’s Disease

Microglial Implications in SARS-CoV-2 Infection and COVID-19: Lessons From Viral RNA Neurotropism and Possible Relevance to Parkinson’s Disease

A to Z of Zika Virus: A Comprehensive Review for Clinicians

Implications of TORCH Diseases in Retinal Development—Special Focus on Congenital Toxoplasmosis

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