Japanese Encephalitis Virus Infection in the Natural Amplifying Host During Pregnancy: Implications for the Emergence of More Pathogenic Virus Variants
Abstract
Emerging viruses—newly discovered viruses or viruses with increasing disease incidence—pose a constant threat to public health. The most recent examples of devastating outbreaks of emerging viruses are Ebola virus, new coronavirus, and Zika virus epidemics. Japanese encephalitis virus (JEV) is the emerging pathogen closely related to Zika virus; it is the most important cause of brain infections in Asia that often leads to death and severe neurological sequela in patients and particularly in children. Almost half of the world’s population lives in territories where JEV is permanently circulating. Like Zika virus, JEV is transmitted via mosquito bite; however, to survive in nature, in addition to humans, JEV requires an animal reservoir that can amplify the virus population. Pigs are natural amplifying hosts for JEV that maintain a transmission cycle from mosquitoes to humans and the existence of the virus. While the proximity of human settlements to pig farms and human contacts with pigs are known as major risks of infection in people, JEV infection in pigs is not well-studied. JEV infection in pregnant pigs is of particular importance. In addition to infection in pregnant adult animals, the virus can infect the placenta—the vital pregnancy organ that supports the life of the developing fetuses—and subsequently fetuses. Pregnancy in animals and humans is a complex process that is associated with maternal immunity adaptation; the physiological goal of this adaptation is to downregulate maternal immune responses and prevent rejection and abortion of fetuses that bear foreign paternal genetic material. Also, placenta and fetuses have modulated and immature immunity that is designed to avoid overreaction against semi-foreign maternal tissues. Altogether, the pregnancy with modulated immunity is an extremely favorable state for viruses, particularly for viruses like JEV with inherited nature to thrive and genetically diversify in the biological environment with underdeveloped and suppressed immune responses. Limited studies on viral infections, e.g., influenza virus infection, in humans and mouse models, showed pregnancy as a risk factor for more severe infection and the emergence of new virus mutants. Thus, maternal immune adaptation during pig pregnancy may also result in less efficient responses to JEV infection, and the emergence of virus mutants with more aggressive infection phenotypes. Also, JEV persistence in the placenta and fetuses with modulated and weak immunity may promote the emergence of more aggressive viruses, increasing chances for the virus spillovers from pigs to humans. In this project, within the frames of Emerging Viral Diseases FY20 PRMRP Topic Area, we will compare immunity against JEV in pregnant and non-pregnant pigs. We will also study how pregnancy and infection in the placenta and fetuses affect JEV evolution and whether it leads to the emergence of more aggressive mutants with a higher potential for transmission from pigs to humans. The project will be the first comparative study addressing whether concurrent JEV infection in three connected but immunologically distinct biological systems—mother, placenta, and fetus—leads to different viral evolution and emergence of mutants with more aggressive characteristics. We will also, for the first time, question whether pregnancy in pigs is a risk factor for JEV spillovers to human populations. We expect that our project will deliver new knowledge that can mobilize scientific efforts to develop a safe vaccine that will be efficient in pregnant pigs benefiting both animal and public health. Also, it may shape public health policies and pig husbandry practices to reduce exposure of pregnant animals to insect vectors and more efficiently plan human contacts with pregnant animals. It will be highly rewarding for patients, families, and food security in developing countries and will decrease the social and economic burden associated with JEV infe
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110014
Entities
People
- Uladzimir Karniychuk
Organizations
- United States Army
- University of Saskatchewan