Microencephaly in fetal piglets following in utero inoculation of Zika virus

Autor: D. Anjema, Jet Kant, L.J.M. van Keulen, P.J. Wichgers Schreur, Jeroen Kortekaas
Rok vydání: 2018
Předmět:
0301 basic medicine
Microcephaly
Swine
Epidemiology
Placenta
Physiology
Zika virus
Pregnancy
Drug Discovery
biology
Zika Virus Infection
Bacteriologie
Brain
Bacteriology
Host Pathogen Interaction & Diagnostics

General Medicine
PE&RC
Virology & Molecular Biology
Flavivirus
Infectious Diseases
medicine.anatomical_structure
In utero
Cerebral cortex
Brain size
RNA
Viral

Female
Immunology
Neuropathology
Microbiology
Article
03 medical and health sciences
Fetus
Virology
medicine
Life Science
Animals
Humans
Host Pathogen Interaction & Diagnostics
Bacteriology
Zika Virus
biology.organism_classification
medicine.disease
Host Pathogen Interactie & Diagnostiek
Virologie & Moleculaire Biologie
Department Experimenteel Dieronderzoek
Disease Models
Animal

030104 developmental biology
Department Experimental Animal Research
Bacteriologie
Host Pathogen Interactie & Diagnostiek

Parasitology
Zdroj: Emerging Microbes & Infections
Emerging Microbes and Infections, 7
Emerging Microbes and Infections 7 (2018)
ISSN: 2222-1751
DOI: 10.1038/s41426-018-0044-y
Popis: Zika virus (ZIKV) is a mosquito-borne flavivirus that became associated with microcephaly in newborns and Guillain-Barré syndrome in adults after its emergence in the Pacific and the Americas in 2015. Newly developed rodent and nonhuman primate models have already revealed important insights into ZIKV-induced neuropathology. Nonhuman primates are phylogenetically closely related to humans and are therefore preferred human surrogates in ZIKV research. However, the use of nonhuman primates, particularly during gestation, raises ethical issues. Considering that pigs also share many anatomical and physiological features with humans, this species may be an attractive alternative human surrogate for ZIKV research. Here, we inoculated 20 porcine fetuses in utero and assessed the effect of ZIKV on brain development 4 weeks later. All inoculated fetuses presented mild to severe neuropathology, characterized by a depletion of neurons in the cerebral cortex. In most cases, neuronal depletion was confined to specific cerebral lobes without affecting brain size, whereas in severe cases a more generalized depletion resulted in microencephaly. Although the virus was widespread in the sows' placenta at the time of necropsy only low levels of viral RNA were detected in fetal brain samples, thereby preventing the identification of primary target cells. Our findings suggest that pigs can be used to study ZIKV-induced neurodevelopmental defects as currently observed in human neonates, varying from stunted brain growth to localized cortical neuronal depletion in the absence of major macroscopic abnormalities.
Databáze: OpenAIRE