Non-human Primate Models to Investigate Mechanisms of Infection-Associated Fetal and Pediatric Injury, Teratogenesis and Stillbirth
Year: 2021
Type: review
Abstract: A wide array of pathogens has the potential to injure the fetus and induce teratogenesis, the process by which mutations in fetal somatic cells lead to congenital malformations. Rubella virus was the first infectious disease to be linked to congenital malformations due to an infection in pregnancy, which can include congenital cataracts, microcephaly, hearing impairment and congenital heart disease. Currently, human cytomegalovirus (HCMV) is the leading infectious cause of congenital malformations globally, affecting 1 in every 200 infants. However, our knowledge of teratogenic viruses and pathogens is far from complete. New emerging infectious diseases may induce teratogenesis, similar to Zika virus (ZIKV) that caused a global pandemic in 2016–2017; thousands of neonates were born with congenital microcephaly due to ZIKV exposurein utero, which also included a spectrum of injuries to the brain, eyes and spinal cord. In addition to congenital anomalies, permanent injury to fetal and neonatal organs, preterm birth, stillbirth and spontaneous abortion are known consequences of a broader group of infectious diseases including group B streptococcus (GBS),Listeria monocytogenes, Influenza A virus (IAV), and Human Immunodeficiency Virus (HIV). Animal models are crucial for determining the mechanism of how these various infectious diseases induce teratogenesis or organ injury, as well as testing novel therapeutics for fetal or neonatal protection. Other mammalian models differ in many respects from human pregnancy including placentation, labor physiology, reproductive tract anatomy, timeline of fetal development and reproductive toxicology. In contrast, non-human primates (NHP) most closely resemble human pregnancy and exhibit key similarities that make them ideal for research to discover the mechanisms of injury and for testing vaccines and therapeutics to prevent teratogenesis, fetal and neonatal injury and adverse pregnancy outcomes (e.g., stillbirth or spontaneous abortion). In this review, we emphasize key contributions of the NHP model pre-clinical research for ZIKV, HCMV, HIV, IAV,L. monocytogenes, Ureaplasma species, and GBS. This work represents the foundation for development and testing of preventative and therapeutic strategies to inhibit infectious injury of human fetuses and neonates.
Source: Frontiers in Genetics
Institutions: University of Washington, Columbia University, Washington State University Spokane, Emory University, Children's Healthcare of Atlanta, Emory National Primate Research Center, Weill Cornell Medicine, University of Wisconsin–Madison, Seattle Children's Research Institute, University of Gothenburg
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,950
Funders: Seattle Children's Research Institute, Children’s Hospital of Wisconsin Research Institute, National Institutes of Health, Yerkes National Primate Research Center, Emory University, NIH Office of the Director, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: FXIIIA production by mast cells for innate immunity, G1951041841, G2542201382, G305976013, G324599786, G376641150, The Maternal-Fetal Interface in Listeria-Induced Pregnancy Loss, G3879473163, Diseases of Public Health Importance Training Grant, G4091721258, G4457992599, G4464103427, G4909129119, INTERDISCIPLINARY PROGRAM IN BACTERIAL PATHOGENESIS, G543310801, Immune Control of Group B Streptococcal Placental, G629796354, G6345000315, Role of the hyaluronidase in GBS Virulence, Targeted Inhibition of Interleukin-1 beta to Prevent Preterm Birth, Cell Wall Biogenesis-Target for new Anti-TB drugs, G6834886916, G7963835266, The origin, predictors, and immune correlates of viral rebound in orally SHIV infected infant monkeys, G8593696555, JAK-STAT Control of Zika Virus-Induced Fetal Injury, Washington National Primate Research Center, Wisconsin National Primate Research Center Support, Training a new generation of vaccinologists, Neurodevelopment after postnatal Zika virus infection in infant macaques, Immunologic strategies to prevent congenital cytomegalovirus transmission and disease in rhesus monkeys, WaNPRC Macaca nemestrina SPF Breeding Colony, Emory National Primate Research Center
OpenAlex ID: W3184501626