Zika: Assocation studies with Guillain-Barre syndrome and neurotropism.
Lead Research Organisation:
University of Glasgow
Department Name: UNLISTED
Abstract
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Technical Summary
The recent global outbreak of Zika virus infection has been linked to severe neurological
phenotypes affecting the peripheral and central nervous systems. While these relationships
are currently undergoing epidemiological monitoring, it seems prudent to assume that these
associations will be confirmed (Cao-Lormeau VM et al., Lancet 2016, in press). In
anticipation, this study will investigate the underlying causation of neurological deficits,
focusing on Guillan-Barré syndrome (GBS); generally considered an autoantibody-mediated
disorder. What is not clear in the current epidemic is whether Zika-GBS is due to direct
infection of neural cells or a post-infectious autoimmune syndrome. We are poised to begin
work to examine the effects immediately of (i) direct viral infection, and shortly of (ii)
humoral factors in serum from Zika-associated GBS and control cases (currently being
obtained with consent from Recife, Brazil by Willison/Kohl), on neural cell viability and
function, using physiologically intact murine living peripheral nerve preparations and cultured
neurons and Schwann cells. Comparative cultures of murine CNS cells will be examined in
parallel to gain insights into the CNS/PNS distinctions in neurological complications. Further,
human sera will be screened to idenitfy autoantibodies to antigens associated with
conventional GBS, to facilitate diagnosis. Once Catergory 3 permissions are granted, we will
substantiate relevant findings in vivo. These studies will lead to a deeper understanding of
the nature of Zika-associated GBS and allow treatment and diagnostic strategies to be
developed.
phenotypes affecting the peripheral and central nervous systems. While these relationships
are currently undergoing epidemiological monitoring, it seems prudent to assume that these
associations will be confirmed (Cao-Lormeau VM et al., Lancet 2016, in press). In
anticipation, this study will investigate the underlying causation of neurological deficits,
focusing on Guillan-Barré syndrome (GBS); generally considered an autoantibody-mediated
disorder. What is not clear in the current epidemic is whether Zika-GBS is due to direct
infection of neural cells or a post-infectious autoimmune syndrome. We are poised to begin
work to examine the effects immediately of (i) direct viral infection, and shortly of (ii)
humoral factors in serum from Zika-associated GBS and control cases (currently being
obtained with consent from Recife, Brazil by Willison/Kohl), on neural cell viability and
function, using physiologically intact murine living peripheral nerve preparations and cultured
neurons and Schwann cells. Comparative cultures of murine CNS cells will be examined in
parallel to gain insights into the CNS/PNS distinctions in neurological complications. Further,
human sera will be screened to idenitfy autoantibodies to antigens associated with
conventional GBS, to facilitate diagnosis. Once Catergory 3 permissions are granted, we will
substantiate relevant findings in vivo. These studies will lead to a deeper understanding of
the nature of Zika-associated GBS and allow treatment and diagnostic strategies to be
developed.
Publications
Cumberworth SL
(2017)
Zika virus tropism and interactions in myelinating neural cell cultures: CNS cells and myelin are preferentially affected.
in Acta neuropathologica communications
Leonhard SE
(2018)
Zika virus infection in the returning traveller: what every neurologist should know.
in Practical neurology
Leonhard SE
(2021)
Guillain-Barré syndrome during the Zika virus outbreak in Northeast Brazil: An observational cohort study.
in Journal of the neurological sciences
Schultz V
(2021)
Zika Virus Infection Leads to Demyelination and Axonal Injury in Mature CNS Cultures.
in Viruses
Wilder-Smith A
(2017)
ZikaPLAN: Zika Preparedness Latin American Network.
in Global health action
Description | Repsonse mode |
Amount | £140,000 (GBP) |
Funding ID | 203680/Z/16/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2016 |
End | 12/2017 |
Title | Zika virus infection leads to demyelination and axonal injury in mature CNS cultures |
Description | These datasets contain cell, myelin, and axon quantification data used for figures and analysis. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | http://researchdata.gla.ac.uk/id/eprint/1049 |
Description | Zika-PLAN, EU funded Framework 2020 project |
Organisation | European Commission |
Country | European Union (EU) |
Sector | Public |
PI Contribution | Member |
Collaborator Contribution | Lead for WP4, member for WP2 |
Impact | Multidisciplinary |
Start Year | 2016 |