Kaur Amitinder, Manuel Tabitha, Moström Matilda, Crooks Chelsea, Davalos Angel, Barfield Richard, Scheef Elizabeth, Kendall Savannah, Midkiff Cecily, Sprehe Lesli, Trexler Macey, Boquet Francis, Shroyer Monica, Danner Victoria, Doyle-Meyers Lara, Weinbaum Carolyn, Mirza Anne, Lammi Stephen, Otero Claire, Lee Marissa, Rogers Layne, Granek Joshua, Owzar Kuoros, Malouli Daniel, Fruh Klaus, Kowalik Timothy, Chan Cliburn, Permar Sallie, Blair Robert
Tulane National Primate Research Center, Tulane University.
Weill Cornell Medicine.
Res Sq. 2025 Apr 23:rs.3.rs-6378923. doi: 10.21203/rs.3.rs-6378923/v1.
Congenital cytomegalovirus (cCMV) is the leading infectious cause of birth defects worldwide, yet immune determinants of protection to inform maternal vaccine design remain elusive due to the lack of a translational animal model. Here, we characterized the outcome of primary rhesus CMV (RhCMV) infection in pregnant, immunocompetent, CMV-naïve rhesus macaques. RhCMV DNA was detected in amniotic fluid and/or fetal tissues in six of 12 (50% placental transmission) dams following early second trimester gestation RhCMV inoculation. Widespread tissue dissemination dominated by one of two inoculated RhCMV strains was present in one fetus (8.3% cCMV disease). Placental transmission was associated with elevated fetal and maternal plasma TNF-alpha and reduced maternal brain-derived neurotrophic factor and IL-10 levels. CMV exposure during pregnancy had a broad impact on the placenta and fetus even in the absence of congenital infection, as evidenced by ubiquitous maternal-fetal interface infection, and reduced placental efficiency and small-for-gestation age fetuses compared to control pregnancies. This model recapitulates key aspects of human cCMV and provides new insights into the complexity of CMV vertical transmission.
先天性巨细胞病毒（cCMV）是全球范围内出生缺陷的主要感染原因，但由于缺乏可转化的动物模型，用于指导母体疫苗设计的保护性免疫决定因素仍然难以捉摸。在此，我们对妊娠、免疫功能正常、未感染CMV的恒河猴进行原发性恒河猴巨细胞病毒（RhCMV）感染的结果进行了表征。在妊娠中期早期接种RhCMV后，12只母猴中有6只（胎盘传播率为50%）的羊水和/或胎儿组织中检测到RhCMV DNA。在一只胎儿中出现了以两种接种的RhCMV菌株之一为主的广泛组织播散（8.3%的cCMV疾病）。胎盘传播与胎儿和母体血浆肿瘤坏死因子-α升高以及母体脑源性神经营养因子和白细胞介素-10水平降低有关。即使在没有先天性感染的情况下，孕期接触CMV对胎盘和胎儿也有广泛影响，这表现为母婴界面普遍感染，与对照妊娠相比，胎盘效率降低和小于胎龄儿。该模型概括了人类cCMV的关键方面，并为CMV垂直传播的复杂性提供了新的见解。
