» Articles » PMID: 34211475

The Placental Response to Guinea Pig Cytomegalovirus Depends Upon the Timing of Maternal Infection

Overview
Journal Front Immunol
Date 2021 Jul 2
PMID 34211475
Citations 3
Authors
Affiliations
Soon will be listed here.
Abstract

Human cytomegalovirus (HCMV) infects the placenta, and these placental infections can cause fetal injury and/or demise. The timing of maternal HCMV infection during pregnancy is a determinant of fetal outcomes, but how development affects the placenta's susceptibility to infection, the likelihood of placental injury post-infection, and the frequency of transplacental HCMV transmission remains unclear. In this study, guinea pig cytomegalovirus (GPCMV) was used to model primary maternal infection and compare the effects of infection at two different times on the placenta. When guinea pigs were infected with GPCMV at either 21- or 35-days gestation (dGA), maternal and placental viral loads, as determined by droplet digital PCR, were not significantly affected by the timing of maternal infection. However, when the transcriptomes of gestational age-matched GPCMV-infected and control placentas were compared, significant infection-associated changes in gene expression were only observed after maternal infection at 35 dGA. Notably, transcripts associated with immune activation (e.g. , , , and ) were upregulated in the infected placenta. A GPCMV-specific hybridization assay detected rare infected cells in the main placenta after maternal infection at either time, and maternal infection at 35 dGA also caused large areas of GPCMV-infected cells in the junctional zone. As GPCMV infection after mid-gestation is known to cause high rates of stillbirth and/or fetal growth restriction, our results suggest that the placenta becomes sensitized to infection-associated injury late in gestation, conferring an increased risk of adverse pregnancy outcomes after cytomegalovirus infection.

Citing Articles

CD4+ but not CD8+ T cells are required for protection against severe guinea pig cytomegalovirus infections.

Rollman T, Berkebile Z, Hicks D, Hatfield J, Chauhan P, Pravetoni M PLoS Pathog. 2024; 20(11):e1012515.

PMID: 39495799 PMC: 11563410. DOI: 10.1371/journal.ppat.1012515.


Pathogenesis of viral infections during pregnancy.

Creisher P, Klein S Clin Microbiol Rev. 2024; 37(2):e0007323.

PMID: 38421182 PMC: 11237665. DOI: 10.1128/cmr.00073-23.


Temporal changes in pathology and viral RNA distribution in guinea pigs following separate infection with two New World Arenaviruses.

Cline C, Zeng X, Bell T, Shaia C, Facemire P, Williams J PLoS Negl Trop Dis. 2023; 17(9):e0011620.

PMID: 37682988 PMC: 10511090. DOI: 10.1371/journal.pntd.0011620.

References
1.
McCarthy R, Martin-Fairey C, Sojka D, Herzog E, Jungheim E, Stout M . Mouse models of preterm birth: suggested assessment and reporting guidelines. Biol Reprod. 2018; 99(5):922-937. PMC: 6297318. DOI: 10.1093/biolre/ioy109. View

2.
Gervasi M, Romero R, Bracalente G, Chaiworapongsa T, Erez O, Dong Z . Viral invasion of the amniotic cavity (VIAC) in the midtrimester of pregnancy. J Matern Fetal Neonatal Med. 2012; 25(10):2002-13. PMC: 3498469. DOI: 10.3109/14767058.2012.683899. View

3.
Liao Y, Smyth G, Shi W . The Subread aligner: fast, accurate and scalable read mapping by seed-and-vote. Nucleic Acids Res. 2013; 41(10):e108. PMC: 3664803. DOI: 10.1093/nar/gkt214. View

4.
Tsuge M, Hida A, Minematsu T, Honda N, Oshiro Y, Yokoyama M . Prospective Cohort Study of Congenital Cytomegalovirus Infection during Pregnancy with Fetal Growth Restriction: Serologic Analysis and Placental Pathology. J Pediatr. 2018; 206:42-48.e2. DOI: 10.1016/j.jpeds.2018.10.003. View

5.
Harrison C, Myers M . Relation of maternal CMV viremia and antibody response to the rate of congenital infection and intrauterine growth retardation. J Med Virol. 1990; 31(3):222-8. DOI: 10.1002/jmv.1890310309. View