Medicine
New virus model reveals how HCMV damages bile ducts
Scientists create human liver cells that can be infected with HCMV, showing the virus's role in causing bile duct disorders.
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1 min read
Human cytomegalovirus (HCMV) is associated with bile duct disorders, but its role in causing these conditions remains unclear. A key question was whether HCMV can directly infect the bile duct epithelium and trigger pathogenesis.
Researchers established a human iPSC-derived cholangiocyte-like cell (CLC) organoid model that can be infected by HCMV. Upon infection, these organoids exhibit reduced growth, a deformed structure, and a loss of barrier function. Bulk RNA sequencing revealed that the HCMV-infected organoids have increased expression of genes involved in epithelial-mesenchymal transition (EMT).
Blockade of TGF-β signalling abrogates the EMT induction effect in the HCMV-infected CLC organoids, suggesting a mechanistic link between viral infection and cellular transformation. Single-cell RNA-seq analysis indicates that HCMV infection occurs in distinct clusters with different gene expression profiles.
The findings are supported by similar patterns of HCMV-DNA + cells in BA patient liver tissues. Notably, two modes of infection have been identified in the CLC organoids, exhibiting both productive and latency-like features. These results provide insight into the mechanisms underlying HCMV's association with bile duct disorders and highlight the importance of cellular responses to viral infection.
1 min read
In a small world of human cells, a virus has been found to disrupt the delicate balance that keeps our organs functioning properly. Human cytomegalovirus (HCMV) is associated with bile duct disorders, which can cause scarring and damage to the bile ducts. This virus affects not only those whose immune systems are weakened but also healthy individuals.
Researchers have created a model of the cells that line the bile ducts using human stem cells. They infected these cells with HCMV and found that it caused the cells to change shape and lose their ability to form a strong barrier. The virus also triggered a process called epithelial-mesenchymal transition, which is involved in the development of scarring tissue.
This discovery matters because it shows that HCMV can directly infect the bile duct cells and cause damage. It also provides new insights into how this virus contributes to bile duct disorders, such as biliary atresia and post-transplant complications. The findings could lead to a better understanding of how to prevent or treat these conditions.
1 min read
In the tiny world of bile ducts, a tiny virus named Human cytomegalovirus (HCMV) was found to cause big problems. HCMV is known to make people sick with things like sclerosing cholangitis and biliary atresia, which are hard to treat.
Scientists created a special model using human cells that mimic the bile ducts. They infected these cells with HCMV and watched what happened. The virus caused the cells to change shape and lose their protective barrier function. It was like the cells were saying goodbye to their healthy selves. But here's the amazing part: the scientists found that when they blocked a certain signal, the cells stopped changing in this way. This discovery helps us understand how HCMV causes problems in people with bile duct disorders.
The people behind the work
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Ye Z et al.
Author
Published in Nature communications
Source: Nature communications
Sources & Verification
Every statement in this story is drawn from the facts below. Each is linked to a primary or reputable source — follow any citation to check it for yourself.
- Human cytomegalovirus (HCMV) is associated with bile duct disorders in immunocompetent and immunocompromised individuals, including sclerosing cholangitis, biliary structures, AIDS cholangiopathy, biliary atresia (BA), and post-transplant biliary complications. Nature communications
- Despite these clinical associations, it remains unknown whether HCMV can directly infect the bile duct epithelium and cause pathogenesis. Nature communications
- Here, we establish a human iPSC-derived cholangiocyte-like cell (CLC) organoid model that can be infected by HCMV, which results in reduced organoid growth, a deformed structure, and a loss of barrier function. Nature communications
- Bulk RNA sequencing (RNA-seq) showed that the HCMV-infected organoids had highly enriched expression of genes involved in the epithelial-mesenchymal transition (EMT) pathway. Nature communications
- Importantly, blockade of TGF-β signalling abrogates the EMT induction effect in the HCMV-infected CLC organoids. Nature communications
- Furthermore, single-cell RNA-seq indicates that HCMV infection occurred in different clusters with distinct viral and host gene expression profiles and the analysis shows increased expression of EMT and TGF-β signalling-related genes. Nature communications
- The findings are confirmed in BA patient liver tissues by examining HCMV-DNA + cells. Nature communications
- Two modes of infection by HCMV are found in these CLC organoids, which show productive and latency-like features. Nature communications
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