Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, Canada.
School of Public Health, University of Saskatchewan, Saskatoon, Canada.
Emerg Microbes Infect. 2023 Dec;12(1):2147021. doi: 10.1080/22221751.2022.2147021.
Congenital virus infections, for example cytomegalovirus and rubella virus infections, commonly affect the central nervous and hematological systems in fetuses and offspring. However, interactions between emerging congenital Zika virus and hematological system-bone marrow and blood-in fetuses and offspring are mainly unknown. Our overall goal was to determine whether silent Zika virus infection can cause functional and molecular footprints in the bone marrow and blood of fetuses and offspring. We specifically focused on silent fetal infection because delayed health complications in initially asymptomatic offspring were previously demonstrated in animal and human studies. Using a well-established porcine model for Zika virus infection and a set of cellular and molecular experimental tools, we showed that silent infection causes multi-organ inflammation in fetuses and local inflammation in the fetal bone marrow. infection also caused footprints in the offspring bone marrow and PBMCs. These findings should be considered in a broader clinical context because of growing concerns about health sequelae in cohorts of children affected with congenital Zika virus infection in the Americas. Understanding virus-induced molecular mechanisms of immune activation and inflammation in fetuses may provide targets for early interventions. Also, identifying early biomarkers of -acquired immunopathology in offspring may help to alleviate long-term sequelae.
先天性病毒感染，例如巨细胞病毒和风疹病毒感染，通常会影响胎儿和后代的中枢神经系统和血液系统。然而，新兴的先天性寨卡病毒与胎儿和后代的血液系统-骨髓和血液之间的相互作用尚不清楚。我们的总体目标是确定潜伏的寨卡病毒感染是否会在胎儿和后代的骨髓和血液中引起功能和分子痕迹。我们特别关注潜伏的胎儿感染，因为之前的动物和人类研究表明，最初无症状的后代会出现延迟的健康并发症。使用一种已建立的寨卡病毒感染猪模型和一系列细胞和分子实验工具，我们表明潜伏感染会导致胎儿多器官炎症和胎儿骨髓局部炎症。感染还会在后代的骨髓和 PBMC 中留下痕迹。由于对美洲受先天性寨卡病毒感染的儿童群体的健康后遗症的担忧不断增加，这些发现应该在更广泛的临床背景下考虑。了解病毒引起的免疫激活和胎儿炎症的分子机制可能为早期干预提供目标。此外，识别后代获得性免疫病理学的早期生物标志物可能有助于减轻长期后遗症。
