Zika Virus-Induced Microcephaly and Its Possible Molecular Mechanism

Faizan, Md Imam; Abdullah, Mohd; Ali, Sher; Naqvi, Irshad H.; Ahmed, Anwar; Parveen, Shama

doi:10.1159/000452950

Cited by 81 publications

(75 citation statements)

References 56 publications

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“…Although it would be naïve to discount effects due to viral strain and host species-specific effects, these observations shed new light on the pathobiology of ZIKV-associated neurological syndromes. First, as the cultures model late foetal and early postnatal stages of development in the human nervous system they are valuable for investigating the pathogenesis of neurological symptoms other than microcephaly, which is thought to result predominantly from infection in the 1st trimester [23, 86]. Second, the vulnerability of myelinating oligodendrocytes might explain the extensive white matter pathology associated with congenital ZIKV syndrome.…”

Section: Discussionmentioning

confidence: 99%

Zika virus tropism and interactions in myelinating neural cell cultures: CNS cells and myelin are preferentially affected

Cumberworth¹,

Barrie²,

Cunningham³

et al. 2017

acta neuropathol commun

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The recent global outbreak of Zika virus (ZIKV) infection has been linked to severe neurological disorders affecting the peripheral and central nervous systems (PNS and CNS, respectively). The pathobiology underlying these diverse clinical phenotypes are the subject of intense research; however, even the principal neural cell types vulnerable to productive Zika infection remain poorly characterised. Here we used CNS and PNS myelinating cultures from wild type and Ifnar1 knockout mice to examine neuronal and glial tropism and short-term consequences of direct infection with a Brazilian variant of ZIKV. Cell cultures were infected pre- or post-myelination for various intervals, then stained with cell-type and ZIKV-specific antibodies. In bypassing systemic immunity using ex vivo culture, and the type I interferon response in Ifnar1 deficient cells, we were able to evaluate the intrinsic infectivity of neural cells. Through systematic quantification of ZIKV infected cells in myelinating cultures, we found that ZIKV infection is enhanced in the absence of the type I interferon responses and that CNS cells are considerably more susceptible to infection than PNS cells. In particular, we demonstrate that CNS axons and myelinating oligodendrocytes are especially vulnerable to injury. These results have implications for understanding the pathobiology of neurological symptoms associated with ZIKV infection. Furthermore, we provide a quantifiable ex vivo infection model that can be used for fundamental and therapeutic studies on viral neuroinvasion and its consequences.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-017-0450-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Zika virus tropism and interactions in myelinating neural cell cultures: CNS cells and myelin are preferentially affected

Cumberworth¹,

Barrie²,

Cunningham³

et al. 2017

acta neuropathol commun

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“…Axl plays a role in Zika virus infection [64,65]. Zika virus is a mosquito-borne flavivirus that was first identified in monkeys in Uganda in 1947 [66].…”

Section: Axl In Zika Virusmentioning

confidence: 99%

“…Blockade of Axl expression or genetic knockdown of Axl reduced virus infection of astrocytes in vitro [65]. Axl facilitated the entry of Zika virus to human foetal neural progenitor cells (hNPCs) during the first trimester of pregnancy, which altered signalling and immune pathways in host cells [64].…”

Section: Axl In Zika Virusmentioning

confidence: 99%

The Role of the TAM Family of Receptor Tyrosine Kinases in Neural Development and Disorders

Zhang¹,

Qi²

2018

Neuropsychiatry

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Tyrosine kinase receptor 3 (Tyro3), Axl, and Mer constitute the TAM family of receptor tyrosine kinases. These receptor tyrosine kinases are characterized by a conserved sequence within the kinase domain and adhesion molecule-like extracellular domains. The TAM family and their shared ligands, growth arrest-specific gene-6 (Gas6) and protein S, are differentially expressed in the developing and adult nervous systems. The TAM family regulates normal cellular processes and plays an important role in nervous system development and diseases, including cell proliferation/survival, cell adhesion and migration, neuronal differentiation, cell apoptosis, myelination, degeneration, and immune regulation. This review summarizes the developing expression of the TAM family and ligands and their function in neural development and nervous system diseases. Further research will be necessary to fully elucidate the function of the TAM family and to evaluate the clinical implications of TAM family expression and activation in nervous system diseases.

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“…ZIKV can be transmitted by transfusion of blood from an infected donor 11,13,14,16,20,26,27,29,37,40,41,43,44,[46][47][48] .…”

Section: Clinical Manifestationsmentioning

confidence: 99%

Zika virus: - a review of the main aspects of this type of arbovirosis

Dias

Sobreira

Martins

et al. 2018

Rev. Soc. Bras. Med. Trop.

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The objective of this study was to integrate findings related to Zika virus from the scientific literature. An integrative review of Medline was conducted, and data search was performed using the Health Sciences Descriptor Zika virus and the following filters: full texts available; studies in humans; full articles; and publications in Portuguese, French, English, and Spanish. After application of the filters, followed by reading of the titles, abstracts, and full texts, 44 studies were included in the review, for which content analysis was performed. A large part of the literature comprised review articles (84%; N=37); the majority was in English (95%, N=42). In 2016, 84% (N=37) of our sample articles was published, while in 2017, 16% (N=7) was published. The main form of viral transmission was thorough the mosquito Aedes aegypti (N=30). In addition, sexual transmission (N=09), transmission through blood transfusion (N=16), vertical transmission (N=21) and transmission from occupational activities (N=03) occurred. It was possible to diagnose the disease by testing blood (N=22), urine (N=14), saliva (N=06), semen/sperm (N=03), cerebrospinal and amniotic fluid, and other tissues (N=02). Symptomatology occurred in 1-5 people (N=10) between 3 and 7 days after a mosquito bite (N=09). Complications observed were Guillain Barré syndrome (N=27); neurological Zika syndrome (N=27); meningitis, meningoencephalitis, and myelitis (N=07); deaths and/or newborns (N=03). The review provides scientific evidence that contributes to the care, planning and implementation of public policies.

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Zika Virus-Induced Microcephaly and Its Possible Molecular Mechanism

Cited by 81 publications

References 56 publications

Zika virus tropism and interactions in myelinating neural cell cultures: CNS cells and myelin are preferentially affected

Zika virus tropism and interactions in myelinating neural cell cultures: CNS cells and myelin are preferentially affected

The Role of the TAM Family of Receptor Tyrosine Kinases in Neural Development and Disorders

Zika virus: - a review of the main aspects of this type of arbovirosis

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