Selective modulation of Wnt-binding receptor tyrosine kinase ROR2 expression by human cytomegalovirus regulates trophoblast migration

Huynh, Kim T.; Zuylen, Wendy J. van; Ford, Caroline; Rawlinson, William D.

doi:10.1099/jgv.0.001179

Cited by 3 publications

(5 citation statements)

References 49 publications

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“…To our knowledge, it is not yet possible to alter the differentiation of SGHPL-4 cells to address the relationship between progenitor cell status and ability of HCMV to replicate in those cells. SGHPL-4 cells are commonly used to study HCMV replication [3,[25][26][27][28][29][30]. Based on the data we present here, future studies using SGHPL-4 cells to investigate HCMV replication may need to consider the cell culture conditions used and how that might influence HCMV protein expression.…”

Section: Discussionmentioning

confidence: 89%

“…SGHPL-4 cells are commonly used to study HCMV replication [3, 25–30]. Based on the data we present here, future studies using SGHPL-4 cells to investigate HCMV replication may need to consider the cell culture conditions used and how that might influence HCMV protein expression.…”

Section: Discussionmentioning

confidence: 94%

“…SGHPL-4 cells are EVT trophoblast cell lines taken from placental tissue of a first trimester pregnancy termination [19]. SGHPL-4 cells had previously been used in several studies of placental trophoblast function upon infection with HCMV [3,[25][26][27][28][29][30][31][32] and were known to support replication of an HCMV GFP reporter mutant [26]. However, how well HCMV replicates in other cells compared to replication in SGHPL-4 was not assessed [26].…”

Section: Hcmv Protein Expression In Sghpl-4 Cellsmentioning

confidence: 99%

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Limited replication of human cytomegalovirus in a trophoblast cell line

Hyde

Sultana

Tran

et al. 2021

Journal of General Virology

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Several viruses, including human cytomegalovirus (HCMV), are thought to replicate in the placenta. However, there is little understanding of the molecular mechanisms involved in HCMV replication in this tissue. We investigated replication of HCMV in the extravillous trophoblast cell line SGHPL-4, a commonly used model of HCMV replication in the placenta. We found limited HCMV protein expression and virus replication in SGHPL-4 cells. This was associated with a lack of trophoblast progenitor cell protein markers in SGHPL-4 cells, suggesting a relationship between trophoblast differentiation and limited HCMV replication. We proposed that limited HCMV replication in trophoblast cells is advantageous to vertical transmission of HCMV, as there is a greater opportunity for vertical transmission when the placenta is intact and functional. Furthermore, when we investigated the replication of other vertically transmitted viruses in SGHPL-4 cells we found some limitation to replication of Zika virus, but not herpes simplex virus. Thus, limited replication of some, but not all, vertically transmitted viruses may be a feature of trophoblast cells.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 94%

Section: Hcmv Protein Expression In Sghpl-4 Cellsmentioning

confidence: 99%

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Limited replication of human cytomegalovirus in a trophoblast cell line

Hyde

Sultana

Tran

et al. 2021

Journal of General Virology

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“…Ex vivo primary term and first trimester placental explant studies implicate altered dualspecificity tyrosine phosphorylation-regulated kinase (DYRK) and Wnt signalling as central to CMV infection-mediated placental dysfunction. Specifically, CMV infection decreased trophoblast migration via elevated expression of Wnt-binding Receptor Tyrosine Kinase Like Orphan Receptor 2 (ROR2) (Huynh et al 2019). Meanwhile, CMV replication within the placenta is dependent on DYRK signalling (Hamilton et al 2018).…”

Section: Srb-australian and New Zealand Placental Research Association (Anzpra) Symposiummentioning

confidence: 99%

Reproductive health research in Australia and New Zealand: highlights from the Annual Meeting of the Society for Reproductive Biology, 2019

Winship

Donoghue

Houston

et al. 2020

Reprod. Fertil. Dev.

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The 2019 meeting of the Society for Reproductive Biology (SRB) provided a platform for the dissemination of new knowledge and innovations to improve reproductive health in humans, enhance animal breeding efficiency and understand the effect of the environment on reproductive processes. The effects of environment and lifestyle on fertility and animal behaviour are emerging as the most important modern issues facing reproductive health. Here, we summarise key highlights from recent work on endocrine-disrupting chemicals and diet- and lifestyle-induced metabolic changes and how these factors affect reproduction. This is particularly important to discuss in the context of potential effects on the reproductive potential that may be imparted to future generations of humans and animals. In addition to key summaries of new work in the male and female reproductive tract and on the health of the placenta, for the first time the SRB meeting included a workshop on endometriosis. This was an important opportunity for researchers, healthcare professionals and patient advocates to unite and provide critical updates on efforts to reduce the effect of this chronic disease and to improve the welfare of the women it affects. These new findings and directions are captured in this review.

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“…Ex vivo infection of placental cultures with cell free HCMV revealed a broader range of infected cells [31]. Placental cells taken from cases of congenital infection demonstrate marked changes in gene expression compared with cells from uninfected counterparts, in particular genes associated with tissue angiogenesis, tissue remodeling, and inflammation [32][33][34][35]. Examination of HCMV infected trophoblasts has also revealed altered compositions in their extracellular matrix, aberrant migration and altered invasive potential compared with uninfected cells [36,37].…”

Section: Introductionmentioning

confidence: 99%

Constitutive Signaling by the Human Cytomegalovirus G Protein Coupled Receptor Homologs US28 and UL33 Enables Trophoblast Migration In Vitro

Davis-Poynter

Farrell

2022

Viruses

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Human cytomegalovirus (HCMV) encodes four homologs of G protein coupled receptors (vGPCRs), of which two, designated UL33 and US28, signal constitutively. UL33 and US28 are also conserved with chemokine receptors: US28 binds numerous chemokine classes, including the membrane bound chemokine, fractalkine; whereas UL33 remains an orphan receptor. There is emerging data that UL33 and US28 each contribute to HCMV associated disease, although no studies to date have reported their potential contribution to aberrant placental physiology that has been detected with HCMV congenital infection. We investigated the signaling repertoire of UL33 and US28 and their potential to enable trophoblast mobilization in vitro. Results demonstrate the constitutive activation of CREB by each vGPCR in ACIM-88 and HTR-8SVneo trophoblasts; constitutive NF-kB activation was detected for US28 only. Constitutive signaling by each vGPCR enabled trophoblast migration. For US28, fractalkine exhibited inverse agonist activity and dampened trophoblast migration. UL33 stimulated expression of both p38 mitogen activated (MAP) and Jun N-terminal (JNK) kinases; while p38 MAP kinase stimulated CREB, JNK was inhibitory, suggesting that UL33 dependent CREB activation was regulated by p38/JNK crosstalk. Given that chemokines and their receptors are important for placental development, these data point to the potential of HCMV UL33 and US28 to interfere with trophoblast responses which are important for normal placental development.

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Selective modulation of Wnt-binding receptor tyrosine kinase ROR2 expression by human cytomegalovirus regulates trophoblast migration

Cited by 3 publications

References 49 publications

Limited replication of human cytomegalovirus in a trophoblast cell line

Limited replication of human cytomegalovirus in a trophoblast cell line

Reproductive health research in Australia and New Zealand: highlights from the Annual Meeting of the Society for Reproductive Biology, 2019

Constitutive Signaling by the Human Cytomegalovirus G Protein Coupled Receptor Homologs US28 and UL33 Enables Trophoblast Migration In Vitro

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