Mild Zika infection in fetuses may cause brain abnormalities in young despite no symptoms

Using a relevant animal model (pigs), University of Saskatchewan researchers have shown that mild Zika virus infection in fetuses can cause abnormal brain development in apparently healthy young animals.

The study, published Nov. 14 in PLOS Pathogens, provides new insights into the potential outcomes of Zika virus infection and could point to new prevention and treatment strategies to alleviate the long-term effects of Zika virus infection.

Spread by the bite of an infected Aedes species mosquito, Zika infection of pregnant mothers can lead to death and decreased brain size (microcephaly) in fetuses, leading to life-long developmental and cognitive impairment.

However, there is growing concern that sub-clinical infections (showing no symptoms) in pregnant mothers can result in brain disorders and delayed neurodevelopmental abnormalities in offspring after birth.

Using the pig as a model, new research at USask’s Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac) has provided direct evidence to support this concern.

“We have demonstrated in a relevant animal model that mild infection in fetuses results in abnormal brain development and impaired immunity in young pigs,” said VIDO-InterVac Director Dr. Volker Gerdts who also participated in the study.

Some of the affected offspring also showed altered behaviour during stress.

“For the first time, we have shown that mild fetal infection can lead to sex-specific brain disease in offspring: male piglets showed more molecular brain abnormalities than female piglets,” said Dr. Uladzimir Karniychuk, senior author of the study, who with colleagues developed the novel animal model.

“We are now able to better understand the disease in fetuses and how it affects health in offspring.”

In 2016, the World Health Organization declared Zika virus a public health emergency. While this emergency declaration has been lifted, Zika infection remains a public health concern. There is currently no approved vaccine or therapy available to combat the infection.

Karniychuk said a next step is to develop an animal model for the study of how to treat and cure infections such as Zika virus in utero. There are currently no in utero therapies for congenital viral infections. Earlier this year, Karniychuk was awarded $250,000 over two years by the federal New Frontiers in Research Fund to undertake this work aimed at reducing the long-term consequences of abnormalities in developing fetuses and the treatment required after birth.

For almost 45 years, VIDO-InterVac has used large animal models to help understand how pathogens cause disease.

“This is another example of how models can improve our understanding of the health consequences of infection, and aid in the development of policy and medical interventions to reduce the long-term impact of infectious diseases,” said Gerdts.

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First author on the study was USask post-doctoral fellow Ivan Trus. The study also involved colleagues from the University of Toronto, Utrecht University in Netherlands, Laval University, and the Canada Microbiology Laboratory in Winnipeg.

Funding was provided by Genome Canada’s Emerging Issues Program through Genome Prairie, the Public Health Agency of Canada, and the Government of Saskatchewan through Innovation Saskatchewan. VIDO-InterVac receives operational funding from the Canada Foundation for Innovation through the Major Science Initiatives funding program and Innovation Saskatchewan.

The paper published in PLOS Pathogens is available here: http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008038

The University of Saskatchewan’s VIDO-InterVac was created in 1975 and has commercialized eight vaccines against infectious disease. The 150-member organization operates using a ISO:9001 certified management system in over $200-million of state-of-the-art containment level 2 and 3 facilities. VIDO-InterVac receives financial support from the Government of Canada, Government of Saskatchewan, industry, foundations and producer groups. http://www.vido.org