scholarly journals Perisynaptic Schwann cells phagocytose nerve terminal debris in a mouse model of Guillain‐Barré syndrome

2020 ◽  
Vol 25 (2) ◽  
pp. 143-151 ◽  
Author(s):  
Madeleine E. Cunningham ◽  
Gavin R. Meehan ◽  
Sophie Robinson ◽  
Denggao Yao ◽  
Rhona McGonigal ◽  
...  
Keyword(s):  
Mouse Model ◽  
Schwann Cells ◽  
Nerve Terminal ◽  
Guillain Barre Syndrome ◽  
Guillain Barré Syndrome ◽  
Perisynaptic Schwann Cells ◽  
Guillain Barré

scholarly journals Zika Virus Encoding Nonglycosylated Envelope Protein Is Attenuated and Defective in Neuroinvasion

2017 ◽  
Vol 91 (23) ◽  
Author(s):  
Arun S. Annamalai ◽  
Aryamav Pattnaik ◽  
Bikash R. Sahoo ◽  
Ezhumalai Muthukrishnan ◽  
Sathish Kumar Natarajan ◽  
...  
Keyword(s):  
Mouse Model ◽  
Zika Virus ◽  
Glycosylation Site ◽  
Human Diseases ◽  
Guillain Barre Syndrome ◽  
Sequence Motif ◽  
Genetic Changes ◽  
E Protein ◽  
Guillain Barré Syndrome ◽  
Guillain Barré

ABSTRACT Zika virus (ZIKV), a mosquito-transmitted flavivirus responsible for sporadic outbreaks of mild and febrile illness in Africa and Asia, reemerged in the last decade causing serious human diseases, including microcephaly, congenital malformations, and Guillain-Barré syndrome. Although genomic and phylogenetic analyses suggest that genetic evolution may have led to the enhanced virulence of ZIKV, experimental evidence supporting the role of specific genetic changes in virulence is currently lacking. One sequence motif, VNDT, containing an N-linked glycosylation site in the envelope (E) protein, is polymorphic; it is absent in many of the African isolates but present in all isolates from the recent outbreaks. In the present study, we investigated the roles of this sequence motif and glycosylation of the E protein in the pathogenicity of ZIKV. We first constructed a stable full-length cDNA clone of ZIKV in a novel linear vector from which infectious virus was recovered. The recombinant ZIKV generated from the infectious clone, which contains the VNDT motif, is highly pathogenic and causes lethality in a mouse model. In contrast, recombinant viruses from which the VNDT motif is deleted or in which the N-linked glycosylation site is mutated by single-amino-acid substitution are highly attenuated and nonlethal. The mutant viruses replicate poorly in the brains of infected mice when inoculated subcutaneously but replicate well following intracranial inoculation. Our findings provide the first evidence that N-linked glycosylation of the E protein is an important determinant of ZIKV virulence and neuroinvasion. IMPORTANCE The recent emergence of Zika virus (ZIKV) in the Americas has caused major worldwide public health concern. The virus appears to have gained significant pathogenicity, causing serious human diseases, including microcephaly and Guillain-Barré syndrome. The factors responsible for the emergence of pathogenic ZIKV are not understood at this time, although genetic changes have been shown to facilitate virus transmission. All isolates from the recent outbreaks contain an N-linked glycosylation site within the viral envelope (E) protein, whereas many isolates of the African lineage virus lack this site. To elucidate the functional significance of glycosylation in ZIKV pathogenicity, recombinant ZIKVs from infectious clones with or without the glycan on the E protein were generated. ZIKVs lacking the glycan were highly attenuated for the ability to cause mortality in a mouse model and were severely compromised for neuroinvasion. Our studies suggest glycosylation of the E protein is an important factor contributing to ZIKV pathogenicity.

The role of complement and complement regulators in mediating motor nerve terminal injury in murine models of Guillain–Barré syndrome

2008 ◽  
Vol 201-202 ◽  
pp. 172-182 ◽  
Author(s):  
Hugh J. Willison ◽  
Susan K. Halstead ◽  
Erin Beveridge ◽  
Femke M.P. Zitman ◽  
Kay N. Greenshields ◽  
...  
Keyword(s):  
Nerve Terminal ◽  
Motor Nerve ◽  
Guillain Barre Syndrome ◽  
Motor Nerve Terminal ◽  
Murine Models ◽  
Guillain Barré Syndrome ◽  
Complement Regulators ◽  
Guillain Barré

scholarly journals Memantine treatment reduces the incidence of flaccid paralysis in a zika virus mouse model of temporary paralysis with similarities to Guillain-Barré syndrome

2020 ◽  
Vol 28 ◽  
pp. 204020662095014
Author(s):  
Venkatraman Siddharthan ◽  
Hong Wang ◽  
Alexandre LR de Oliveira ◽  
Xin Dai ◽  
John D Morrey
Keyword(s):  
Mouse Model ◽  
Receptor Antagonist ◽  
Zika Virus ◽  
Clinical Evidence ◽  
Flaccid Paralysis ◽  
Guillain Barre Syndrome ◽  
Aspartate Receptor ◽  
Memantine Treatment ◽  
Guillain Barré Syndrome ◽  
Guillain Barré

Clinical evidence suggests that Zika virus contributes to Guillain-Barré syndrome that causes temporary paralysis. We utilized a recently described Zika virus mouse model of temporary flaccid paralysis to address the hypothesis that treatment with an N-methyl-D-aspartate receptor antagonist, memantine, can reduce the incidence of paralysis. Aged interferon alpha/beta-receptor knockout mice were used because of their sublethal susceptibility to Zika virus infection. Fifteen to twenty-five percent of mice infected with a Puerto Rico strain of Zika virus develop acute flaccid paralysis beginning at days 8–9 and peaked at days 10–12. Mice recover from paralysis within a week of onset. In two independent studies, twice daily oral administration of memantine at 60 mg/kg/day on days 4 through 9 after viral challenge significantly reduced the incidence of paralysis. No efficacy was observed with treatments from days 9 through 12. Memantine treatment in cell culture or mice did not affect viral titers. These data indicate that early treatment of memantine before onset of paralysis is efficacious, but treatments beyond the onset of paralysis were not efficacious. The effect of this N-methyl-D-aspartate receptor antagonist on the incidence of Zika virus-induced paralysis may provide guidance for investigations on the mechanism of paralysis.

scholarly journals The Neuroimmunology of Guillain-Barré Syndrome and the Potential Role of an Aging Immune System

2021 ◽  
Vol 12 ◽  
Author(s):  
Kathleen M. Hagen ◽  
Shalina S. Ousman
Keyword(s):  
Immune System ◽  
Schwann Cells ◽  
Potential Role ◽  
Immune Cell ◽  
Guillain Barre Syndrome ◽  
Age Related ◽  
Guillain Barré Syndrome ◽  
Autoimmune Condition ◽  
Guillain Barré

Guillain-Barré syndrome (GBS) is a paralyzing autoimmune condition affecting the peripheral nervous system (PNS). Within GBS there are several variants affecting different aspects of the peripheral nerve. In general, there appears to be a role for T cells, macrophages, B cells, and complement in initiating and perpetuating attacks on gangliosides of Schwann cells and axons. Of note, GBS has an increased prevalence and severity with increasing age. In addition, there are alterations in immune cell functioning that may play a role in differences in GBS with age alongside general age-related declines in reparative processes (e.g., delayed de-differentiation of Schwann cells and decline in phagocytic ability of macrophages). The present review will explore the immune response in GBS as well as in animal models of several variants of the disorder. In addition, the potential involvement of an aging immune system in contributing to the increased prevalence and severity of GBS with age will be theorized.

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