Primary HSV-2 Infection in Early Pregnancy Results in Transplacental Viral Transmission and Dose-Dependent Adverse Pregnancy Outcomes in a Novel Mouse Model
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 dur...
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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/10/1929 |
| _version_ | 1797512979071107072 |
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| author | Allison M. Felker Philip Nguyen Charu Kaushic |
| author_facet | Allison M. Felker Philip Nguyen Charu Kaushic |
| author_sort | Allison M. Felker |
| collection | DOAJ |
| description | 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 10<sup>2</sup>–10<sup>5</sup> 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. |
| first_indexed | 2024-03-10T06:08:16Z |
| format | Article |
| id | doaj.art-2e03413e8d4647f5a3657f5e2861e8bc |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T06:08:16Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-2e03413e8d4647f5a3657f5e2861e8bc2023-11-22T20:18:12ZengMDPI AGViruses1999-49152021-09-011310192910.3390/v13101929Primary HSV-2 Infection in Early Pregnancy Results in Transplacental Viral Transmission and Dose-Dependent Adverse Pregnancy Outcomes in a Novel Mouse ModelAllison M. Felker0Philip Nguyen1Charu Kaushic2McMaster Immunology Research Centre, Michael G. DeGroote Centre for Learning and Discovery, McMaster University, Hamilton, ON L8S 4L8, CanadaMcMaster Immunology Research Centre, Michael G. DeGroote Centre for Learning and Discovery, McMaster University, Hamilton, ON L8S 4L8, CanadaMcMaster Immunology Research Centre, Michael G. DeGroote Centre for Learning and Discovery, McMaster University, Hamilton, ON L8S 4L8, CanadaHerpes 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 10<sup>2</sup>–10<sup>5</sup> 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.https://www.mdpi.com/1999-4915/13/10/1929HSV-2viral infectionpregnancyplacental pathologyneonatal herpesmouse model |
| spellingShingle | Allison M. Felker Philip Nguyen Charu Kaushic Primary HSV-2 Infection in Early Pregnancy Results in Transplacental Viral Transmission and Dose-Dependent Adverse Pregnancy Outcomes in a Novel Mouse Model Viruses HSV-2 viral infection pregnancy placental pathology neonatal herpes mouse model |
| title | Primary HSV-2 Infection in Early Pregnancy Results in Transplacental Viral Transmission and Dose-Dependent Adverse Pregnancy Outcomes in a Novel Mouse Model |
| title_full | Primary HSV-2 Infection in Early Pregnancy Results in Transplacental Viral Transmission and Dose-Dependent Adverse Pregnancy Outcomes in a Novel Mouse Model |
| title_fullStr | Primary HSV-2 Infection in Early Pregnancy Results in Transplacental Viral Transmission and Dose-Dependent Adverse Pregnancy Outcomes in a Novel Mouse Model |
| title_full_unstemmed | Primary HSV-2 Infection in Early Pregnancy Results in Transplacental Viral Transmission and Dose-Dependent Adverse Pregnancy Outcomes in a Novel Mouse Model |
| title_short | Primary HSV-2 Infection in Early Pregnancy Results in Transplacental Viral Transmission and Dose-Dependent Adverse Pregnancy Outcomes in a Novel Mouse Model |
| title_sort | primary hsv 2 infection in early pregnancy results in transplacental viral transmission and dose dependent adverse pregnancy outcomes in a novel mouse model |
| topic | HSV-2 viral infection pregnancy placental pathology neonatal herpes mouse model |
| url | https://www.mdpi.com/1999-4915/13/10/1929 |
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