The BeWo cell line derived from a human placental choriocarcinoma is permissive for respiratory syncytial virus infection

Velázquez-Cervantes, M.A.; Martínez-Castillo, Macario; González-García, Luis Didier; Vargas-Pavía, Tania Allin; Martínez-Salazar, Martha; Mancilla-Herrera, Ismael; León-Reyes, Guadalupe; García‐Cordero, Julio; Helguera-Repetto, Addy Cecilia; León-Juárez, Moisés

doi:10.1007/s11262-019-01646-2

Cited by 3 publications

(6 citation statements)

References 33 publications

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“…To our knowledge, this is the first evidence of infection of human placenta by a respiratory virus. It also confirms and completes our previous report [21]–recently confirmed by an independent lab [22]—showing RSV infection of BeWo cells, a human choriocarcinoma cell line that retains some structural and functional characteristics of the placental trophoblast. Indeed, of the three major cell types found in the human placenta, the cytotrophoblast exhibited the lowest susceptibility to this infection, whereas fibroblasts and Hofbauer cells were significantly more permissive.…”

Section: Discussionsupporting

confidence: 91%

Respiratory syncytial virus exhibits differential tropism for distinct human placental cell types with Hofbauer cells acting as a permissive reservoir for infection

Bokun

Moore

et al. 2019

PLoS ONE

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BackgroundRespiratory syncytial virus (RSV) is capable of transient viremia and extrapulmonary dissemination. Recently, this virus has been identified in fetal cord blood, suggesting the possibility of in utero acquisition in humans. Here, we assess permissivity and kinetics of RSV replication in primary human placental cells, examine their potential to transfer this infection to neighboring cells, and measure the inflammatory response evoked by the virus.Methods and findingsHuman placental villus tissue was collected immediately upon delivery and processed for isolation of placental cytotrophoblast, fibroblast, and macrophage (Hofbauer) cells. Isolated cells were infected with a recombinant RSV-A2 strain (rrRSV) expressing red fluorescent protein (RFP) and analyzed by fluorescence microscopy, Western blot, and quantitative PCR (qPCR). Based on RFP expression, rrRSV exhibited differential tropism for the three major placental cell types. Placental fibroblasts and Hofbauer cells were permissive and supported productive rrRSV replication. While infected cytotrophoblast cells expressed viral glycoprotein (G protein), only limited RSV replication was detected. Importantly, qPCR and fluorescence-focused unit assay revealed that the viral progeny remains trapped within infected Hofbauer cells for up to 30 days, with no release into surrounding media. Yet, Hofbauer cells passed the infection onto overlaid naïve 16HBE cells, suggesting contact-dependent trans-infection. Lastly, a significant increase in proinflammatory cytokines, particularly IL-6, TNF-alpha, and IFN-gamma was measured in the supernatant of infected Hofbauer cells by multiplex cytokine assay and conventional ELISA.ConclusionsThis study demonstrates that RSV can replicate in human placenta, exhibits differential tropism for distinct placental cell types, can be stored and transferred to neighboring cells by Hofbauer cells, and elicits an inflammatory response. It also supports the hypothesis that this respiratory virus can be vertically transferred to the fetus and potentially affect its development and the outcome of pregnancies.

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Section: Discussionsupporting

confidence: 91%

Respiratory syncytial virus exhibits differential tropism for distinct human placental cell types with Hofbauer cells acting as a permissive reservoir for infection

Bokun

Moore

et al. 2019

PLoS ONE

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“…Importantly, recent evidence shows that hRSV can infect placental cells, cross the placental barrier, and, therein, be vertically transmitted to the fetus [18,24,40]. One of the unknown relevant issues is the MIA effect on hRSV infection, which is essential since MIA has been associated with cognitive and behavioral impairment and neuropsychiatric illnesses such as SCZ and ASD [32,53,57,94].…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, other important parameters such as white blood cells and C-reactive protein in serum were high in the neonates with anti-hRSV antibodies compared to controls [41]. These observations led to studies using the BeWoo cell line (human choriocarcinoma cells), where the peak of the viral load detected was at 24 hrs post-infection applying MOI 5 [18]. Moreover, the hRSV infection of BeWoo cells produce infective particle and express the known receptor for the virus, TLR4, and nucleolin [18].…”

Section: Hrsv Infection During Pregnancy and Effects On The Newbornmentioning

confidence: 99%

“…These observations led to studies using the BeWoo cell line (human choriocarcinoma cells), where the peak of the viral load detected was at 24 hrs post-infection applying MOI 5 [18]. Moreover, the hRSV infection of BeWoo cells produce infective particle and express the known receptor for the virus, TLR4, and nucleolin [18]. Furthermore, the hRSV infection was evaluated in three cell types (cytotrophoblast, fibroblasts, and Hofbauer cells) obtained from human placental villous tissue [42].…”

Section: Hrsv Infection During Pregnancy and Effects On The Newbornmentioning

confidence: 99%

“…Although the primary targets of the infection with hRSV are the epithelial lung cells, it has been demonstrated that hRSV can also infect cells in the central nervous system (CNS) and the placenta [16][17][18]. Several reports suggest that the infection with hRSV can cause neurological symptoms, such as encephalitis and encephalopathies, leading to long-term neurological consequences [19][20][21].…”

Section: Introductionmentioning

confidence: 99%

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Potential Neurocognitive Symptoms Due to Respiratory Syncytial Virus Infection

2021

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Respiratory infections are among the major public health burdens, especially during winter. Along these lines, the human respiratory syncytial virus (hRSV) is the principal viral agent causing acute lower respiratory tract infections leading to hospitalization. The pulmonary manifestations due to hRSV infection are bronchiolitis and pneumonia, where the population most affected are infants and the elderly. However, recent evidence suggests that hRSV infection can impact the mother and fetus during pregnancy. Studies have indicated that hRSV can infect different cell types from the placenta and even cross the placenta barrier and infect the fetus. In addition, it is known that infections during the gestational period can lead to severe consequences for the development of the fetus due not only to a direct viral infection but also because of maternal immune activation (MIA). Furthermore, it has been described that the development of the central nervous system (CNS) of the fetus can be affected by the inflammatory environment of the uterus caused by viral infections. Increasing evidence supports the notion that hRSV could invade the CNS and infect nervous cells, such as microglia, neurons, and astrocytes, promoting neuroinflammation. Moreover, it has been described that the hRSV infection can provoke neurological manifestations, including cognitive impairment and behavioral alterations. Here, we will review the potential effect of hRSV in brain development and the potential long-term neurological sequelae.

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Collateral Damage in the Placenta during Viral Infection in Pregnancy: A Possible Mechanism for Vertical Transmission and an Adverse Pregnancy Outcome

Cruz-Holguín,

González-García,

Velázquez-Cervantes

et al. 2024

Diseases

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In mammals, the placenta is a connection between a mother and a new developing organism. This tissue has a protective function against some microorganisms, transports nutrients, and exchanges gases and excretory substances between the mother and the fetus. Placental tissue is mainly composed of chorionic villi functional units called trophoblasts (cytotrophoblasts, the syncytiotrophoblast, and extravillous trophoblasts). However, some viruses have developed mechanisms that help them invade the placenta, causing various conditions such as necrosis, poor perfusion, and membrane rupture which, in turn, can impact the development of the fetus and put the mother’s health at risk. In this study, we collected the most relevant information about viral infection during pregnancy which can affect both the mother and the fetus, leading to an increase in the probability of vertical transmission. Knowing these mechanisms could be relevant for new research in the maternal–fetal context and may provide options for new therapeutic targets and biomarkers in fetal prognosis.

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The BeWo cell line derived from a human placental choriocarcinoma is permissive for respiratory syncytial virus infection

Cited by 3 publications

References 33 publications

Respiratory syncytial virus exhibits differential tropism for distinct human placental cell types with Hofbauer cells acting as a permissive reservoir for infection

Respiratory syncytial virus exhibits differential tropism for distinct human placental cell types with Hofbauer cells acting as a permissive reservoir for infection

Potential Neurocognitive Symptoms Due to Respiratory Syncytial Virus Infection

Collateral Damage in the Placenta during Viral Infection in Pregnancy: A Possible Mechanism for Vertical Transmission and an Adverse Pregnancy Outcome

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