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Article

Primary HSV-2 Infection in Early Pregnancy Results in Transplacental Viral Transmission and Dose-Dependent Adverse Pregnancy Outcomes in a Novel Mouse Model

1
McMaster Immunology Research Centre, Michael G. DeGroote Centre for Learning and Discovery, McMaster University, Hamilton, ON L8S 4L8, Canada
2
Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada
*
Authors to whom correspondence should be addressed.
Academic Editor: Julia A. Beatty
Received: 27 August 2021 / Revised: 20 September 2021 / Accepted: 23 September 2021 / Published: 25 September 2021
(This article belongs to the Special Issue In Vivo Mouse Models of Human Viral Infections)
Herpes simplex virus type 2 (HSV-2) infection affects 24 million births annually and is associated with adverse pregnancy outcomes, including neonatal herpes; however, the mechanisms underlying in utero transmission of HSV-2 are largely unknown. We examined the effects of primary HSV-2 infection during early pregnancy on gestational outcomes in a novel, clinically relevant mouse model. Pregnant C57BL/6 mice were infected intravaginally with 102–105 pfu/mL HSV-2 on gestation day (gd) 4.5. Controls were infected, nonpregnant, diestrus-staged mice and pregnant, uninfected mice. Compared to nonpregnant mice, pregnant mice were 100-fold more susceptible to HSV-2 infection. Three days post-inoculation (gd7.5), viral DNA was present in implantation sites, but pregnancy outcomes were largely unaffected by infection. Eight days post-inoculation (gd12.5), HSV-2 DNA persisted in placental tissues, resulting in inflammation and hemorrhage. Fetal and placental weights were reduced and fetal loss was observed with high viral doses. HSV-2 DNA and increased expression of pro-inflammatory mediators were detected in fetal tissues at gd12.5, signifying viral transmission and fetal infection, even with low viral doses. This mouse model shows a dose-dependent effect of primary HSV-2 infection on pregnancy outcomes and suggests that fetal loss may occur due to placental inflammation, thus providing valuable insight into in utero transmission of HSV-2. View Full-Text
Keywords: HSV-2; viral infection; pregnancy; placental pathology; neonatal herpes; mouse model HSV-2; viral infection; pregnancy; placental pathology; neonatal herpes; mouse model
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MDPI and ACS Style

Felker, A.M.; Nguyen, P.; Kaushic, C. Primary HSV-2 Infection in Early Pregnancy Results in Transplacental Viral Transmission and Dose-Dependent Adverse Pregnancy Outcomes in a Novel Mouse Model. Viruses 2021, 13, 1929. https://0-doi-org.brum.beds.ac.uk/10.3390/v13101929

AMA Style

Felker AM, Nguyen P, Kaushic C. Primary HSV-2 Infection in Early Pregnancy Results in Transplacental Viral Transmission and Dose-Dependent Adverse Pregnancy Outcomes in a Novel Mouse Model. Viruses. 2021; 13(10):1929. https://0-doi-org.brum.beds.ac.uk/10.3390/v13101929

Chicago/Turabian Style

Felker, Allison M., Philip Nguyen, and Charu Kaushic. 2021. "Primary HSV-2 Infection in Early Pregnancy Results in Transplacental Viral Transmission and Dose-Dependent Adverse Pregnancy Outcomes in a Novel Mouse Model" Viruses 13, no. 10: 1929. https://0-doi-org.brum.beds.ac.uk/10.3390/v13101929

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