Low Susceptibility of Rubella Virus in First-Trimester Trophoblast Cell Lines

Pham, Ngan Thi Kim; Trinh, Quang Duy; Takada, Kazuko; Komine‐Aizawa, Shihoko; Hayakawa, Satoshi

doi:10.3390/v14061169

Cited by 4 publications

(4 citation statements)

References 21 publications

(22 reference statements)

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“…Current articles have reported that trophoblast cells are resistant to many viral infections, including RuV (Bayer et al, 2015;Trinh et al, 2018). Our latest experimental results showed that RuV has low infectivity to the first-trimester trophoblast cell lines HTR-8/SVneo and Swan.71 in vitro (Pham et al, 2022). Early studies suggested that transplacental RuV infection targets fetal endothelial cells and Hofbauer cells instead of trophoblasts (Perelygina et al, 2013(Perelygina et al, , 2015.…”

Section: Discussionmentioning

confidence: 90%

“…We recently discovered that RuV has low infectivity to the first-trimester trophoblast cell lines HTR-8/SVneo and Swan.71 in vitro, suggesting that there might be other factors affecting the infectivity of RuV to these cells (Pham et al, 2022). Searching for such possible factors led us to hypothesize that ER stress may play a role in RuV infection in early pregnancy.…”

Section: Introductionmentioning

confidence: 99%

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Enhancement of Rubella Virus Infection in Immortalized Human First-Trimester Trophoblasts Under Low-Glucose Stress Conditions

et al. 2022

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Rubella virus (RuV) infections in pregnant women, especially first-trimester infections, can lead to congenital rubella syndrome (CRS). However, the mechanisms of fetal RuV infection are not completely understood, and it is not observed in every pregnant woman infected with RuV. As gestational diabetes mellitus is a risk factor for congenital viral infections, we investigated the possible roles of hypoglycemia-related endoplasmic reticulum (ER) stress as a key factor for vertical RuV infection using immortalized human first-trimester trophoblasts. Low-glucose stress was induced prior to RuV infection by culturing HTR-8/SVneo and Swan.71 cells in low-glucose (LG) medium for 24 h or high-glucose medium for 6 h and then LG medium for an additional 18 h. Clinically isolated RuV was inoculated at a multiplicity of infection of 5 to 10. The intracellular localization of the RuV capsid protein was investigated 24 to 48 h post-infection (pi) with flow cytometry (FCM) analysis and fluorescence microscopy. Viral progeny production was monitored by FCM analysis. Increases in RuV infection in LG-induced ER-stressed trophoblasts were observed. No significant increase in apoptosis of RuV-infected cells was noted at days 2 and 5 pi, and substantial viral progeny production was observed until day 5 pi. An approximate fivefold increase in viral binding was noted for the LG-stressed cells. Although the detailed mechanisms underlying viral entry into LG-stressed cells are not known and require further investigation, these findings suggest that a certain degree of LG stress in early pregnancy may facilitate infection and cause CRS.

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Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Enhancement of Rubella Virus Infection in Immortalized Human First-Trimester Trophoblasts Under Low-Glucose Stress Conditions

et al. 2022

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“…It is well established that for most of the CRS cases, the infection and vertical transmission occurred in the first trimester [ 9 ]. However, in vitro studies showed that RuV has low infectivity in trophoblasts and suggest that some factors may affect the infection in the first trimester [ 8 , 13 , 92 , 117 ].…”

Section: Viral Infections In Pregnancymentioning

confidence: 99%

“…However, the mechanisms for which these viral infections affect trophoblasts, a natural barrier to prevent the fetus from being infected due to a virally infected mother, are not well understood. Trophoblasts are generally well-known for their resistance or low susceptibility to various viruses [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Roles of TGF-β1 in Viral Infection during Pregnancy: Research Update and Perspectives

Trinh

Pham

Takada

et al. 2023

IJMS

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Transforming growth factor-beta 1 (TGF-β1) is a pleiotropic growth factor playing various roles in the human body including cell growth and development. More functions of TGF-β1 have been discovered, especially its roles in viral infection. TGF-β1 is abundant at the maternal–fetal interface during pregnancy and plays an important function in immune tolerance, an essential key factor for pregnancy success. It plays some critical roles in viral infection in pregnancy, such as its effects on the infection and replication of human cytomegalovirus in syncytiotrophoblasts. Interestingly, its role in the enhancement of Zika virus (ZIKV) infection and replication in first-trimester trophoblasts has recently been reported. The above up-to-date findings have opened one of the promising approaches to studying the mechanisms of viral infection during pregnancy with links to corresponding congenital syndromes. In this article, we review our current and recent advances in understanding the roles of TGF-β1 in viral infection. Our discussion focuses on viral infection during pregnancy, especially in the first trimester. We highlight the mutual roles of viral infection and TGF-β1 in specific contexts and possible functions of the Smad pathway in viral infection, with a special note on ZIKV infection. In addition, we discuss promising approaches to performing further studies on this topic.

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TGF-β1 Promotes Zika Virus Infection in Immortalized Human First-Trimester Trophoblasts via the Smad Pathway

Trinh

Pham

Takada

et al. 2022

Cells

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The Zika virus (ZIKV) is well known for causing congenital Zika syndrome if the infection occurs during pregnancy; however, the mechanism by which the virus infects and crosses the placenta barrier has not been completely understood. In pregnancy, TGF-β1 is abundant at the maternal–fetal interface. TGF-β1 has been reported to enhance rubella virus binding and infection in human lung epithelial cells. Therefore, in this study, we investigate the role of TGF-β1 in ZIKV infection in the immortalized human first-trimester trophoblasts, i.e., Swan.71. The cells were treated with TGF-β1 (10 ng/mL) for two days before being inoculated with the virus (American strain PRVABC59) at a multiplicity of infection of five. The results showed an enhancement of ZIKV infection, as demonstrated by the immunofluorescent assay and flow cytometry analysis. Such enhanced infection effects were abolished using SB431542 or SB525334, inhibitors of the TGF-β/Smad signaling pathway. An approximately 2-fold increase in the virus binding to the studied trophoblasts was found. In the presence of the Smad inhibitors, virus replication was significantly suppressed. An enhancement in Tyro3 and AXL (receptors for ZIKV) expression induced by TGF-β1 was also noted. The results suggest that TGF-β1 promotes the virus infection via the Smad pathway. Further studies should be carried out to clarify the underlying mechanisms of these findings.

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Low Susceptibility of Rubella Virus in First-Trimester Trophoblast Cell Lines

Cited by 4 publications

References 21 publications

Enhancement of Rubella Virus Infection in Immortalized Human First-Trimester Trophoblasts Under Low-Glucose Stress Conditions

Enhancement of Rubella Virus Infection in Immortalized Human First-Trimester Trophoblasts Under Low-Glucose Stress Conditions

Roles of TGF-β1 in Viral Infection during Pregnancy: Research Update and Perspectives

TGF-β1 Promotes Zika Virus Infection in Immortalized Human First-Trimester Trophoblasts via the Smad Pathway

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