%0 Journal Article %1 10.1371/journal.ppat.1007235 %A Koestner, W %A Spanier, J %A Klause, T %A Tegtmeyer, P K %A Becker, J %A Herder, V %A Borst, K %A Todt, D %A Lienenklaus, S %A Gerhauser, I %A Detje, C N %A Geffers, R %A Langereis, M A %A Vondran, F W R %A Yuan, Q %A van Kuppeveld, F J M %A Ott, M %A Staeheli, P %A Steinmann, E %A Baumgartner, W %A Wacker, F %A Kalinke, U %D 2018 %I Public Library of Science %J PLOS Pathog %K ott %N 8 %P 1-23 %T Interferon-beta expression and type I interferon receptor signaling of hepatocytes prevent hepatic necrosis and virus dissemination in Coxsackievirus B3-infected mice %U https://doi.org/10.1371/journal.ppat.1007235 %V 14 %X Author summary CVB3 belongs to human enteroviruses and is transmitted through the fecal-oral route. Infections with CVB3 are mostly unnoticed or cause flu-like symptoms, however, they can also cause severe disease, such as myocarditis, pancreatitis, and hepatitis. Although CVB3 does not efficiently trigger plasmacytoid dendritic cells, which are the main IFN-I producers in many other virus infections, IFNAR signaling plays a crucial role in CVB3 control. Therefore, we investigated which cells are stimulated to produce IFN-I following CVB3 infection and which cell types have to be IFNAR-triggered in order to confer anti-viral protection. We found that upon CVB3 infection IFN-β was mainly expressed within the liver, especially by hepatocytes and not by liver resident macrophages. This was corroborated by in vitro CVB3 infection experiments with primary murine and human hepatocytes. Interestingly, IFNAR signaling of hepatocytes was required to control the virus. Collectively, our data indicate that hepatocytes, and not immune cells, are the key innate effector cells that are relevant for the control of CVB3 infection.

@article{10.1371/journal.ppat.1007235, abstract = {Author summary CVB3 belongs to human enteroviruses and is transmitted through the fecal-oral route. Infections with CVB3 are mostly unnoticed or cause flu-like symptoms, however, they can also cause severe disease, such as myocarditis, pancreatitis, and hepatitis. Although CVB3 does not efficiently trigger plasmacytoid dendritic cells, which are the main IFN-I producers in many other virus infections, IFNAR signaling plays a crucial role in CVB3 control. Therefore, we investigated which cells are stimulated to produce IFN-I following CVB3 infection and which cell types have to be IFNAR-triggered in order to confer anti-viral protection. We found that upon CVB3 infection IFN-β was mainly expressed within the liver, especially by hepatocytes and not by liver resident macrophages. This was corroborated by in vitro CVB3 infection experiments with primary murine and human hepatocytes. Interestingly, IFNAR signaling of hepatocytes was required to control the virus. Collectively, our data indicate that hepatocytes, and not immune cells, are the key innate effector cells that are relevant for the control of CVB3 infection.}, added-at = {2018-09-18T15:08:39.000+0200}, author = {Koestner, W and Spanier, J and Klause, T and Tegtmeyer, P K and Becker, J and Herder, V and Borst, K and Todt, D and Lienenklaus, S and Gerhauser, I and Detje, C N and Geffers, R and Langereis, M A and Vondran, F W R and Yuan, Q and van Kuppeveld, F J M and Ott, M and Staeheli, P and Steinmann, E and Baumgartner, W and Wacker, F and Kalinke, U}, biburl = {https://www.bibsonomy.org/bibtex/2e9350a17c009df41f06efb385b2daf02/ott}, interhash = {77df4aa5a829c2394c616f33ede4affa}, intrahash = {e9350a17c009df41f06efb385b2daf02}, journal = {PLOS Pathog}, keywords = {ott}, month = {08}, number = 8, pages = {1-23}, publisher = {Public Library of Science}, pubmedurl = {https://www.ncbi.nlm.nih.gov/pubmed/30075026}, timestamp = {2018-09-18T15:08:39.000+0200}, title = {Interferon-beta expression and type I interferon receptor signaling of hepatocytes prevent hepatic necrosis and virus dissemination in Coxsackievirus B3-infected mice}, url = {https://doi.org/10.1371/journal.ppat.1007235}, volume = 14, year = 2018 }