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A mouse model of HIV in pregnancy: the EcoHIV+ pregnancy model
Michelle Ranjbar1, Ingrid Hsieh1, Maud Collomb2
1Institute of Medical Sciences, University of Toronto, Toronto, Canada.
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.
