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How Zika virus induces congenital microcephaly

Press release | 11 Dec 2017 - 17h00 | By INSERM PRESS OFFICE
Immunology, inflammation, infectiology and microbiology

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A team of researchers from ZIKAlliance discovers a specific mechanism of the infection

(Liège-Paris, December 11, 2017) –  Epidemiological studies show that in utero fetal infection with the Zika virus (ZIKV) may lead to microcephaly, an irreversible congenital malformation of the brain characterized by an incomplete development of the cerebral cortex. However, the mecha- nism of Zika virus-associated microcephaly remains unclear. An international team of researchers within the European consortium ZIKAlliance (coordinated by Inserm in France) has identified a specific mechanism leading to this microcephaly. Their findings are published this week in Nature Neuroscience.

To understand this mechanism, the scientific team led by Dr. Laurent Nguyen (frs-F.N.R.S., GIGA Neuroscience, University of Liège) and Prof. Marc Lecuit (Institut Pasteur, Inserm, University Paris Descartes, Necker Children’s Hospital, AP-HP) combined analysis of human fetuses infected with Zika virus, cultures of human neuronal stem cells and mice embryos. They showed that ZIKV infec- tion of cortical progenitors (stem cells for cortical neurons) controlling neurogenesis triggers a stress in the endoplasmic reticulum (where some of the cellular proteins and lipids are synthe- tized) in the embryonic brain, inducing signals in response to incorrect protein conformation (re- ferred to as “unfolded protein response”).

When it reaches the brain, Zika virus infects neuronal stem cells, which will generate fewer neu- rons, and by inducing chronic stress in the endoplasmic reticulum, it promotes apoptosis, i.e. the early death of these neuronal cells. These two combined mechanisms explain why the cerebral cortex of infected fetuses becomes deficient in neurons and is therefore smaller in size.

“These discoveries demonstrate a hypothesis that we had made following a basic research study we had just carried out in our laboratory, and thus confirm the physiological importance of the unfolded protein response in the control of neurogenesis,”  says Laurent Nguyen.

Researchers continued their studies on mice by administering inhibitors  of protein-folding  re- sponse in cortical progenitors and found that this inhibited the development of microcephaly in mice embryos infected with Zika virus.

Furthermore, the defects observed are specific to an infection by ZIKV, as other neurotropical vi- ruses of the flavivirus family (West Nile virus, yellow fever,…) did not cause microcephaly, in con- trast to Zika virus.

According to Prof. Marc Lecuit, “these results illustrate how studying fundamental biological pro- cesses is an essential step in understanding the mechanisms of infections, and lead to novel thera- peutic strategies.”

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Press release – Inserm press room How Zika virus induces congenital microcephaly Link : https://presse.inserm.fr/en/francais-comment-le-virus-zika-induit-la-microcephalie-congenitale/30192/
Medias
Press Contact

ULiège

Dr. Laurent Nguyen, Laboratory for Molecular Regulation  of Neurogenesis,  GIGA Neuroscience, University of Liège, Phone +32 4 366 59 87, lnguyen@uliege.be

Via Press Office, +32 4 366 52 17, press@uliege.be

 

Institut Pasteur / Inserm / Paris Descartes/AP-HP

Prof. Marc Lecuit, Institut Pasteur, Infection Biology Unit, Inserm U1117

Department of Infectious and Tropical Diseases, Necker Children’s Hospital, AP-HP Via Press Offices, presse@pasteur.fr / service.presse@aphp.fr

Sources

Stress-induced unfolded protein response contributes to Zika virus-associated microcephaly, Nature

Neuroscience, doi 10.1038/s41593-017-0038-4 www.nature.com/natureneuroscience

 

A propos du virus Zika

L’infection par virus Zika est une maladie transmise par les moustiques, similaire à la dengue, la fièvre jaune ou la maladie du Nil occidental. Bien que l’infection entraîne souvent chez l’adulte des symptômes bénins, y compris de la fièvre et une éruption cutanée, il a été démontré ces derniers mois que le virus Zika peut être transmis de la mère à son fœtus, et provoquer des microcéphalies. Il peut également être la cause de paralysies graves pouvant atteindre les muscles respiratoires et entraîner la mort chez l’adulte (syndrome de Guillain-Barré).

 

UE : 45 millions d’euros pour la recherche et la prévention du virus Zika

L’UE soutient la recherche afin de développer des traitements, des diagnostics et des vaccins ainsi qu’une meilleure évaluation des risques pour le virus Zika. La majorité du financement (30 millions

€) est consacré à trois consortiums de recherche : ZikaPLAN (11 M €), coordonné par l’Université

d’Umeå en Suède, ZIKAction (7 M €), coordonné par la Fondation PENTA en Italie, et ZIKAlliance (12 M €), coordonné par l’Inserm  en France. Des chercheurs européens mais aussi du Brésil, d’autres pays d’Amérique latine et des Caraïbes collaborent dans ces consortiums pour mieux connaître l’infection par le virus Zika et ses conséquences pour les femmes enceintes, les nouveau- nés et les adultes, ainsi que pour développer des tests de diagnostic améliorés et déterminer les meilleures options pour le traitement et la prévention.

 

Plus d’infos : www.zikalliance.tghn.org

@ZIKAlliance

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