In 2015 the news spread quickly of a devastating epidemic in Brazil, caused by the Zika virus (ZIKV). The virus then spread to other parts of South and North America, as well as some Pacific islands and Southeast Asia. ZIKV is spread by a bite from an infected mosquito, and can also be spread via sexual activity and blood transfusion.
ZIKV is particularly distressing because it can be transmitted from an infected pregnant woman to her fetus and can cause severe brain anomalies including microcephaly. There are currently no approved vaccines or therapeutics.
Fortunately, The Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac) at the University of Saskatchewan in Saskatoon has some of the largest and most advanced infrastructure in the world to work with infectious agents, including biosafety level 3 pathogens (level 4 is the highest level).
Genome Prairie – through Genome Canada’s emerging issues program – was able to respond quickly with scientific research funding for Dr. Uladzimir (Vladi) Karniychuk and his team at VIDO-InterVac to develop a swine model of ZIKV infection to investigate how the virus causes disease. Support for the project was also provided by Innovation Saskatchewan, the Public Health Agency of Canada and VIDO-InterVac.
Karniychuk is a veterinarian, with a focus on virology, originally from Belarus in eastern Europe. He has completed a PhD from Ghent University in Belgium, as well as postdoctoral work with McMaster University in Hamilton and the University Health Network in Toronto.
“For our research, the benefit of working with the porcine animal model is that the gestation period in pigs is 115 days, which approximates human pregnancy better than small animal models. Also, each pig carries 12 to 15 fetuses. Importantly for ZIKV research, the porcine fetal and neonatal brain development is very similar to brain development in humans,” says Karniychuk.
In humans, ZIKV outcomes vary from the birth of an asymptomatic infant to very abnormal development and severe brain lesions. There are concerns that fetuses infected with ZIKV in utero and born without any apparent symptoms can still develop health consequences later in life (for example mental illnesses such as schizophrenia).
“The cases of microcephalic infants with ZIKV that appeared in the media presented the most extreme cases of microcephaly. For this reason, visible signs of congenital Zika syndrome may be just the tip of the iceberg. Babies can appear healthy but suffer as time passes and remain impaired forever.”
“Therefore, animal models are important to understand health sequelae in symptomatic and likely more widespread asymptomatic offspring and to develop interventions against in utero infections and long-term health problems,” explains Karniychuk.
In collaboration with the University of Toronto, Karniychuk’s team profiled the whole genome expression in the brains of neonatal piglets affected with subclinical in utero ZIKV infection and control animals that were not infected. This important work was done using next generation sequencing (NGS) technology.
After ZIKV infection, the researchers found many genes and biological processes were affected in the brains of deceptively healthy neonates. This means that while some of the animals did not visibly have issues at birth, their brains were still abnormal.
“As an emerging issue, we were able to work intensely on this study for two years. I was grateful for the help of Genome Prairie during the grant writing process, especially the organization’s internal and external review process,” says Karniychuk.
The project was a team effort that included 12 animal care technicians, four veterinarians and core laboratory technicians from VIDO-InterVac. With the necessary containment infrastructure, VIDO-InterVac has the expertise to safely and humanely study infectious diseases using animal models.
ZIKV continues to be a concern in parts of the globe such as India and, potentially, Africa. In addition, different strains of the virus have begun to appear in humans and the impact of this work is ongoing.
The findings of Karniychuk and his team have been published in the journals Virulence, EBioMedicine, and Emerging Microbes and Infections. Karniychuk looks forward to continuing his research in the areas of viruses, vaccines and in utero interventions.