Cellular stress is triggered by tick-borne encephalitis virus and limits the virus replication in PMJ2-R mouse macrophage cell line
Viral infection may represent a stress condition to the host cell. Cells react to it by triggering the defence programme to restore homeostasis and these events may in turn impact the viral replication. The knowledge about tick-borne encephalitis virus (TBEV) infection-associated stress is limited....
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Ticks and Tick-Borne Diseases |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1877959X23001504 |
| _version_ | 1827587970053439488 |
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| author | Zuzana Beránková Ritesh Khanna Markéta Spěváková Helena Langhansová Jan Kopecký Jaroslava Lieskovská |
| author_facet | Zuzana Beránková Ritesh Khanna Markéta Spěváková Helena Langhansová Jan Kopecký Jaroslava Lieskovská |
| author_sort | Zuzana Beránková |
| collection | DOAJ |
| description | Viral infection may represent a stress condition to the host cell. Cells react to it by triggering the defence programme to restore homeostasis and these events may in turn impact the viral replication. The knowledge about tick-borne encephalitis virus (TBEV) infection-associated stress is limited. Here we investigated the interplay between TBEV infection and stress pathways in PMJ2-R mouse macrophage cell line, as macrophages are the target cells in early phases of TBEV infection. First, to determine how stress influences TBEV replication, the effect of stress inducers H2O2 and tunicamycin (TM) was tested. Viral multiplication was decreased in the presence of both stress inducers suggesting that the stress and cellular stress responses restrict the virus replication. Second, we investigated the induction of oxidative stress and endoplasmic reticulum (ER) stress upon TBEV infection. The level of oxidative stress was interrogated by measuring the reactive oxygen species (ROS). ROS were intermittently increased in infected cells at 12 hpi and at 72 hpi. As mitochondrial dysfunction may result in increased ROS level, we evaluated the mitochondrial homeostasis by measuring the mitochondrial membrane potential (MMP) and found that TBEV infection induced the hyperpolarization of MMP. Moreover, a transient increase of gene expression of stress-induced antioxidative enzymes, like p62, Gclm and Hmox1, was detected. Next, we evaluated the ER stress upon TBEV infection by analysing unfolded protein responses (UPR). We found that infection induced gene expression of two general sensors BiP and CHOP and activated the IRE1 pathway of UPR. Finally, since the natural transmission route of TBEV from its tick vector to the host is mediated via tick saliva, the impact of tick saliva from Ixodes ricinus on stress pathways in TBEV-infected cells was tested. We observed only marginal potentiation of UPR pathway.In conclusion, we found that TBEV infection of PMJ2-R cells elicits the changes in redox balance and triggers cellular stress defences, including antioxidant responses and the IRE1 pathway of UPR. Importantly, our results revealed the negative effect of stress-evoked events on TBEV replication and only marginal impact of tick saliva on stress cellular pathways. |
| first_indexed | 2024-03-09T00:26:04Z |
| format | Article |
| id | doaj.art-2aa11dd396f5406cae8672fc9230d7ab |
| institution | Directory Open Access Journal |
| issn | 1877-9603 |
| language | English |
| last_indexed | 2024-03-09T00:26:04Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ticks and Tick-Borne Diseases |
| spelling | doaj.art-2aa11dd396f5406cae8672fc9230d7ab2023-12-12T04:34:44ZengElsevierTicks and Tick-Borne Diseases1877-96032024-01-01151102269Cellular stress is triggered by tick-borne encephalitis virus and limits the virus replication in PMJ2-R mouse macrophage cell lineZuzana Beránková0Ritesh Khanna1Markéta Spěváková2Helena Langhansová3Jan Kopecký4Jaroslava Lieskovská5Department of Medical Biology, Faculty of Science, University of South Bohemia, Branišovská 1760, CZ-37005 České Budějovice, Czech RepublicDepartment of Medical Biology, Faculty of Science, University of South Bohemia, Branišovská 1760, CZ-37005 České Budějovice, Czech RepublicDepartment of Medical Biology, Faculty of Science, University of South Bohemia, Branišovská 1760, CZ-37005 České Budějovice, Czech RepublicDepartment of Medical Biology, Faculty of Science, University of South Bohemia, Branišovská 1760, CZ-37005 České Budějovice, Czech RepublicDepartment of Medical Biology, Faculty of Science, University of South Bohemia, Branišovská 1760, CZ-37005 České Budějovice, Czech RepublicCorresponding author.; Department of Medical Biology, Faculty of Science, University of South Bohemia, Branišovská 1760, CZ-37005 České Budějovice, Czech RepublicViral infection may represent a stress condition to the host cell. Cells react to it by triggering the defence programme to restore homeostasis and these events may in turn impact the viral replication. The knowledge about tick-borne encephalitis virus (TBEV) infection-associated stress is limited. Here we investigated the interplay between TBEV infection and stress pathways in PMJ2-R mouse macrophage cell line, as macrophages are the target cells in early phases of TBEV infection. First, to determine how stress influences TBEV replication, the effect of stress inducers H2O2 and tunicamycin (TM) was tested. Viral multiplication was decreased in the presence of both stress inducers suggesting that the stress and cellular stress responses restrict the virus replication. Second, we investigated the induction of oxidative stress and endoplasmic reticulum (ER) stress upon TBEV infection. The level of oxidative stress was interrogated by measuring the reactive oxygen species (ROS). ROS were intermittently increased in infected cells at 12 hpi and at 72 hpi. As mitochondrial dysfunction may result in increased ROS level, we evaluated the mitochondrial homeostasis by measuring the mitochondrial membrane potential (MMP) and found that TBEV infection induced the hyperpolarization of MMP. Moreover, a transient increase of gene expression of stress-induced antioxidative enzymes, like p62, Gclm and Hmox1, was detected. Next, we evaluated the ER stress upon TBEV infection by analysing unfolded protein responses (UPR). We found that infection induced gene expression of two general sensors BiP and CHOP and activated the IRE1 pathway of UPR. Finally, since the natural transmission route of TBEV from its tick vector to the host is mediated via tick saliva, the impact of tick saliva from Ixodes ricinus on stress pathways in TBEV-infected cells was tested. We observed only marginal potentiation of UPR pathway.In conclusion, we found that TBEV infection of PMJ2-R cells elicits the changes in redox balance and triggers cellular stress defences, including antioxidant responses and the IRE1 pathway of UPR. Importantly, our results revealed the negative effect of stress-evoked events on TBEV replication and only marginal impact of tick saliva on stress cellular pathways.http://www.sciencedirect.com/science/article/pii/S1877959X23001504FlavivirusTick-borne encephalitis virusCellular stressOxidative stressMitochondrial homeostasisStress on endoplasmic reticulum |
| spellingShingle | Zuzana Beránková Ritesh Khanna Markéta Spěváková Helena Langhansová Jan Kopecký Jaroslava Lieskovská Cellular stress is triggered by tick-borne encephalitis virus and limits the virus replication in PMJ2-R mouse macrophage cell line Ticks and Tick-Borne Diseases Flavivirus Tick-borne encephalitis virus Cellular stress Oxidative stress Mitochondrial homeostasis Stress on endoplasmic reticulum |
| title | Cellular stress is triggered by tick-borne encephalitis virus and limits the virus replication in PMJ2-R mouse macrophage cell line |
| title_full | Cellular stress is triggered by tick-borne encephalitis virus and limits the virus replication in PMJ2-R mouse macrophage cell line |
| title_fullStr | Cellular stress is triggered by tick-borne encephalitis virus and limits the virus replication in PMJ2-R mouse macrophage cell line |
| title_full_unstemmed | Cellular stress is triggered by tick-borne encephalitis virus and limits the virus replication in PMJ2-R mouse macrophage cell line |
| title_short | Cellular stress is triggered by tick-borne encephalitis virus and limits the virus replication in PMJ2-R mouse macrophage cell line |
| title_sort | cellular stress is triggered by tick borne encephalitis virus and limits the virus replication in pmj2 r mouse macrophage cell line |
| topic | Flavivirus Tick-borne encephalitis virus Cellular stress Oxidative stress Mitochondrial homeostasis Stress on endoplasmic reticulum |
| url | http://www.sciencedirect.com/science/article/pii/S1877959X23001504 |
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