17β-Oestradiol Protects from Hepatitis C Virus Infection through Induction of Type I Interferon
Background and Aims: Sex hormones are widely recognised to act as protective factors against several viral infections. Specifically, females infected by the hepatitis C virus display higher clearance rates and reduced disease progression than those found in males. Through modulation of particle rele...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/8/1806 |
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| author | Matteo Nazzareno Barbaglia James Michael Harris Artem Smirnov Michela Emma Burlone Cristina Rigamonti Mario Pirisi Rosalba Minisini Andrea Magri |
| author_facet | Matteo Nazzareno Barbaglia James Michael Harris Artem Smirnov Michela Emma Burlone Cristina Rigamonti Mario Pirisi Rosalba Minisini Andrea Magri |
| author_sort | Matteo Nazzareno Barbaglia |
| collection | DOAJ |
| description | Background and Aims: Sex hormones are widely recognised to act as protective factors against several viral infections. Specifically, females infected by the hepatitis C virus display higher clearance rates and reduced disease progression than those found in males. Through modulation of particle release and spread, 17β-oestradiol controls HCV’s life cycle. We investigated the mechanism(s) behind oestrogen’s antiviral effect. Methods: We used cell culture-derived hepatitis C virus in in vitro assays to evaluate the effect of 17β-oestradiol on the innate immune response. Host immune responses were evaluated by enumerating gene transcripts via RT-qPCR in cells exposed to oestrogen in the presence or absence of viral infection. Antiviral effects were determined by focus-forming unit assay or HCV RNA quantification. Results: Stimulation of 17β-oestradiol triggers a pre-activated antiviral state in hepatocytes, which can be maintained for several hours after the hormone is removed. This induction results in the elevation of several innate immune genes, such as interferon alpha and beta, tumour necrosis factor, toll-like receptor 3 and interferon regulatory factor 5. We demonstrated that this pre-activation of immune response signalling is not affected by a viral presence, and the antiviral state can be ablated using an interferon-alpha/beta receptor alpha inhibitor. Finally, we proved that the oestrogen-induced stimulation is essential to generate an antiviral microenvironment mediated by activation of type I interferons. Conclusion: Resulting in viral control and suppression, 17β-oestradiol induces an interferon-mediated antiviral state in hepatocytes. Oestrogen-stimulated cells modulate the immune response through secretion of type I interferon, which can be countered by blocking interferon-alpha/beta receptor alpha signalling. |
| first_indexed | 2024-03-09T03:41:32Z |
| format | Article |
| id | doaj.art-8436e94da2d945a38a385c0d831beb59 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T03:41:32Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-8436e94da2d945a38a385c0d831beb592023-12-03T14:39:44ZengMDPI AGViruses1999-49152022-08-01148180610.3390/v1408180617β-Oestradiol Protects from Hepatitis C Virus Infection through Induction of Type I InterferonMatteo Nazzareno Barbaglia0James Michael Harris1Artem Smirnov2Michela Emma Burlone3Cristina Rigamonti4Mario Pirisi5Rosalba Minisini6Andrea Magri7Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, ItalyNuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UKLudwig Institute for Cancer Research, University of Oxford, Oxford OX3 7DQ, UKDepartment of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, ItalyDepartment of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, ItalyDepartment of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, ItalyDepartment of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, ItalyDepartment of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, ItalyBackground and Aims: Sex hormones are widely recognised to act as protective factors against several viral infections. Specifically, females infected by the hepatitis C virus display higher clearance rates and reduced disease progression than those found in males. Through modulation of particle release and spread, 17β-oestradiol controls HCV’s life cycle. We investigated the mechanism(s) behind oestrogen’s antiviral effect. Methods: We used cell culture-derived hepatitis C virus in in vitro assays to evaluate the effect of 17β-oestradiol on the innate immune response. Host immune responses were evaluated by enumerating gene transcripts via RT-qPCR in cells exposed to oestrogen in the presence or absence of viral infection. Antiviral effects were determined by focus-forming unit assay or HCV RNA quantification. Results: Stimulation of 17β-oestradiol triggers a pre-activated antiviral state in hepatocytes, which can be maintained for several hours after the hormone is removed. This induction results in the elevation of several innate immune genes, such as interferon alpha and beta, tumour necrosis factor, toll-like receptor 3 and interferon regulatory factor 5. We demonstrated that this pre-activation of immune response signalling is not affected by a viral presence, and the antiviral state can be ablated using an interferon-alpha/beta receptor alpha inhibitor. Finally, we proved that the oestrogen-induced stimulation is essential to generate an antiviral microenvironment mediated by activation of type I interferons. Conclusion: Resulting in viral control and suppression, 17β-oestradiol induces an interferon-mediated antiviral state in hepatocytes. Oestrogen-stimulated cells modulate the immune response through secretion of type I interferon, which can be countered by blocking interferon-alpha/beta receptor alpha signalling.https://www.mdpi.com/1999-4915/14/8/1806oestrogenhepatitis Cinterferon |
| spellingShingle | Matteo Nazzareno Barbaglia James Michael Harris Artem Smirnov Michela Emma Burlone Cristina Rigamonti Mario Pirisi Rosalba Minisini Andrea Magri 17β-Oestradiol Protects from Hepatitis C Virus Infection through Induction of Type I Interferon Viruses oestrogen hepatitis C interferon |
| title | 17β-Oestradiol Protects from Hepatitis C Virus Infection through Induction of Type I Interferon |
| title_full | 17β-Oestradiol Protects from Hepatitis C Virus Infection through Induction of Type I Interferon |
| title_fullStr | 17β-Oestradiol Protects from Hepatitis C Virus Infection through Induction of Type I Interferon |
| title_full_unstemmed | 17β-Oestradiol Protects from Hepatitis C Virus Infection through Induction of Type I Interferon |
| title_short | 17β-Oestradiol Protects from Hepatitis C Virus Infection through Induction of Type I Interferon |
| title_sort | 17β oestradiol protects from hepatitis c virus infection through induction of type i interferon |
| topic | oestrogen hepatitis C interferon |
| url | https://www.mdpi.com/1999-4915/14/8/1806 |
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