Basolateral entry and release of Crimean-Congo hemorrhagic fever virus in polarized MDCK-1 cells
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A Choroid Plexus Epithelial Cell-based Model of the Human Blood-Cerebrospinal Fluid Barrier to Study Bacterial Infection from the Basolateral Side
Published on: May 6, 2016
Anne-Marie Connolly-Andersen1, Karl-Erik Magnusson, Ali Mirazimi
1Swedish Institute for Infectious Disease Control, Centre for Microbiological Preparedness, SE-171 82 Solna, Sweden.
Insights
Crimean-Congo hemorrhagic fever virus (CCHFV) enters and exits polarized epithelial cells from the basolateral side. This study found no evidence that CCHFV affects tight junction function, suggesting other mechanisms cause hemorrhage.
Area of Science:
- Virology
- Cell Biology
- Pathogenesis
Background:
- Crimean-Congo hemorrhagic fever virus (CCHFV) causes severe disease with high mortality.
- Hemorrhage is a key symptom, but its underlying mechanisms, particularly viral effects on vascular integrity, remain unclear.
- The role of polarized epithelial cells in CCHFV entry, release, and spread is unknown.
Purpose of the Study:
- To investigate the entry and release sites of CCHFV in polarized epithelial cells.
- To determine if CCHFV affects the function of tight junctions (TJ), which are critical for vascular homeostasis.
- To elucidate potential mechanisms contributing to CCHFV-induced hemorrhage.
Main Methods:
- Utilized Madin-Darby canine kidney 1 (MDCK-1) epithelial cells to model polarized cell barriers.
- Assessed CCHFV entry and release through basolateral and apical surfaces.
- Measured transepithelial electrical resistance (TEER) to evaluate TJ integrity.
- Examined the localization of TJ proteins ZO-1 and occludin via immunofluorescence.
Main Results:
- CCHFV demonstrated preferential entry via the basolateral side of MDCK-1 cells.
- Basolateral release of CCHFV from polarized epithelial cells was confirmed.
- No significant alterations in TEER were observed, indicating CCHFV replication did not disrupt TJ function.
- Localization of TJ proteins ZO-1 and occludin remained unaffected in infected cells.
Conclusions:
- CCHFV utilizes the basolateral route for both entry and release in polarized epithelial cells.
- Contrary to hypotheses, CCHFV replication does not appear to compromise tight junction integrity in this model.
- The mechanisms of CCHFV-induced hemorrhage likely involve pathways independent of direct tight junction disruption.
Abstract:
Crimean-Congo hemorrhagic fever virus (CCHFV) is an etiological agent of a disease with mortality rates in patients averaging 30%. The disease is characterized by fever, myalgia, and hemorrhage. Mechanisms underlying the hemorrhage have to our knowledge not been elucidated for CCHFV. Possibly, a direct or indirect viral effect on tight junctions (TJ) could cause the hemorrhage observed in patients, as TJ play a crucial role in vascular homeostasis and can cause leakage upon deregulation. Moreover, there is no knowledge regarding the site of entry and release of CCHFV in polarized epithelial cells. Such cells represent a barrier to virus dissemination within the host, and as a site of viral entry and release, they could play a key role in further spread. For the first time, we have shown preferential basolateral entry of CCHFV in Madin-Darby canine kidney 1 (MDCK-1) epithelial cells. Furthermore, we demonstrated basolateral release of CCHFV in polarized epithelial cells. Interestingly, by measuring transepithelial electrical resistance, we found no effect of CCHFV replication on the function of TJ in this study. Neither did we observe any difference in the localization of the TJ proteins ZO-1 and occludin in CCHFV-infected cells compared to mock-infected cells.
