小鼠妊娠期HIV模型：EcoHIV+妊娠模型。

IF 10.8 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

EBioMedicine Pub Date : 2025-09-23 DOI:10.1016/j.ebiom.2025.105943

Michelle Ranjbar, Ingrid Hsieh, Maud Collomb, Lena Serghides

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引用次数: 0

摘要

背景：怀孕期间感染艾滋病毒对孕产妇和胎儿健康构成风险。在人类身上确定潜在的机制可能具有挑战性。虽然存在人源化小鼠模型，但它们不适合用于妊娠研究，这凸显了对替代模型的需求。本文介绍了一种嵌合性嗜生态HIV病毒感染小鼠妊娠模型。方法：雌性C57BL/6J小鼠分别在交配前7天和妊娠期11.5天感染或模拟感染2.5 × 106 pg/mL EcoHIV。监测大坝增重情况。怀孕的水坝在GD14.5或GD18.5时被安乐死。记录胎儿和胎盘重量、胎儿生存力、产仔数和吸收率。计算胎盘效率（胎儿与胎盘重量比）。从母体血液、脾脏和胎儿体分离的RNA中，采用qPCR定量检测HIV Gag表达来评估感染情况。研究结果：在妊娠前感染的母鼠中有90%可检测到EcoHIV感染，在妊娠期间感染的母鼠中有100%可检测到EcoHIV感染。感染EcoHIV的小鼠的母体体重增加较低，怀孕期间感染的小鼠体重增加幅度最大。与GD18.5的对照组相比，EcoHIV感染与胎儿体重明显降低、胎盘重量增加和胎盘效率降低有关。围产期生态艾滋病毒传播发生在部分胎儿中，产仔平均传播率从怀孕期间感染的3.1%到怀孕前感染的17.9%不等。解释：EcoHIV妊娠模型模拟了临床方面，可以成为了解妊娠期HIV感染及其对母婴健康影响的宝贵工具。本项目由加拿大卫生研究院（CIHR）资助（编号：PJT-180630， PJH-192202, HAL-157984）。MR获得了NSERC/CIHR加拿大研究生奖学金，医学科学研究所奖学金和新发与大流行感染联盟（EPIC）博士奖的工资支持。LS是加拿大妇幼保健和艾滋病毒一级研究主席。

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A mouse model of HIV in pregnancy: the EcoHIV+ pregnancy model.

Background: HIV infection during pregnancy poses risks to maternal and foetal health. Identifying underlying mechanisms can be challenging in humans. While humanised mouse models exist, they are unsuitable for pregnancy research, highlighting the need for alternative models. Here we introduce a mouse pregnancy model using infection with EcoHIV, a chimeric ecotropic HIV virus.

Methods: Female C57BL/6J mice were infected with 2.5 × 10⁶ pg/mL EcoHIV, or mock infected, either 7 days prior to mating, or on gestational day (GD) 11.5. Dam weight gain was monitored. Pregnant dams were euthanised on GD14.5 or GD18.5. Foetal and placenta weights, foetal viability, litter size and resorptions were recorded. Placenta efficiency (foetal to placental weight ratio) was calculated. Infection was assessed using HIV Gag expression quantified by qPCR in RNA isolated from maternal blood, spleen, and foetal body.

Findings: EcoHIV infection was detectable in 90% of dams infected prior to pregnancy and 100% of dams infected during pregnancy. Maternal weight gain was lower in EcoHIV infected mice, with the greatest reduction seen in those infected during pregnancy. EcoHIV infection was associated with significantly lower foetal weight, higher placenta weight, and lower placenta efficiency compared to controls at GD18.5. Perinatal EcoHIV transmission occurred in a portion of foetuses, with litter average transmission rates ranging from 3.1% with infection during pregnancy to 17.9% with infection prior to pregnancy.

Interpretation: The EcoHIV pregnancy model mimics clinical aspects and can be a valuable tool to understand HIV infection in pregnancy and its consequences on maternal and foetal health.

Funding: This project has been funded by the Canadian Institutes of Health Research (CIHR) (award # PJT-180630, PJH-192202, HAL-157984). MR received salary support from NSERC/CIHR Canada Graduate Scholarship, Institute of Medical Science Fellowship Award, and Emerging & Pandemic Infections Consortium (EPIC) Doctoral Award. LS holds a Tier 1 Canada Research Chair in Maternal-Child Health and HIV.

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来源期刊

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.