Differential Response Following Infection of Mouse CNS with Virulent and Attenuated Vaccinia Virus Strains
Viral infections of the central nervous system (CNS) lead to a broad range of pathologies. CNS infections with Orthopox viruses have been mainly documented as an adverse reaction to smallpox vaccination with vaccinia virus. To date, there is insufficient data regarding the mechanisms underlying path...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-02-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/7/1/19 |
| _version_ | 1811187983640952832 |
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| author | Tomer Israely Nir Paran Noam Erez Lilach Cherry Hadas Tamir Hagit Achdout Boaz Politi Ofir Israeli Galia Zaide Inbar Cohen-Gihon Einat B. Vitner Shlomo Lustig Sharon Melamed |
| author_facet | Tomer Israely Nir Paran Noam Erez Lilach Cherry Hadas Tamir Hagit Achdout Boaz Politi Ofir Israeli Galia Zaide Inbar Cohen-Gihon Einat B. Vitner Shlomo Lustig Sharon Melamed |
| author_sort | Tomer Israely |
| collection | DOAJ |
| description | Viral infections of the central nervous system (CNS) lead to a broad range of pathologies. CNS infections with Orthopox viruses have been mainly documented as an adverse reaction to smallpox vaccination with vaccinia virus. To date, there is insufficient data regarding the mechanisms underlying pathological viral replication or viral clearance. Therefore, informed risk assessment of vaccine adverse reactions or outcome prediction is limited. This work applied a model of viral infection of the CNS, comparing neurovirulent with attenuated strains. We followed various parameters along the disease and correlated viral load, morbidity, and mortality with tissue integrity, innate and adaptive immune response and functionality of the blood⁻brain barrier. Combining these data with whole brain RNA-seq analysis performed at different time points indicated that neurovirulence is associated with host immune silencing followed by induction of tissue damage-specific pathways. In contrast, brain infection with attenuated strains resulted in rapid and robust induction of innate and adaptive protective immunity, followed by viral clearance and recovery. This study significantly improves our understanding of the mechanisms and processes determining the consequence of viral CNS infection and highlights potential biomarkers associated with such outcomes. |
| first_indexed | 2024-04-11T14:11:47Z |
| format | Article |
| id | doaj.art-c3713e1cc39c4172a6fa9366898a6a17 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-04-11T14:11:47Z |
| publishDate | 2019-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-c3713e1cc39c4172a6fa9366898a6a172022-12-22T04:19:41ZengMDPI AGVaccines2076-393X2019-02-01711910.3390/vaccines7010019vaccines7010019Differential Response Following Infection of Mouse CNS with Virulent and Attenuated Vaccinia Virus StrainsTomer Israely0Nir Paran1Noam Erez2Lilach Cherry3Hadas Tamir4Hagit Achdout5Boaz Politi6Ofir Israeli7Galia Zaide8Inbar Cohen-Gihon9Einat B. Vitner10Shlomo Lustig11Sharon Melamed12Department of Infectious Diseases, Israel Institute of Biological Research (IIBR), Ness-Ziona, IsraelDepartment of Infectious Diseases, Israel Institute of Biological Research (IIBR), Ness-Ziona, IsraelDepartment of Infectious Diseases, Israel Institute of Biological Research (IIBR), Ness-Ziona, IsraelDepartment of Infectious Diseases, Israel Institute of Biological Research (IIBR), Ness-Ziona, IsraelDepartment of Infectious Diseases, Israel Institute of Biological Research (IIBR), Ness-Ziona, IsraelDepartment of Infectious Diseases, Israel Institute of Biological Research (IIBR), Ness-Ziona, IsraelDepartment of Infectious Diseases, Israel Institute of Biological Research (IIBR), Ness-Ziona, IsraelDepartment of Biochemistry and Molecular Genetics, Israel Institute of Biological Research (IIBR), Ness-Ziona, IsraelDepartment of Biochemistry and Molecular Genetics, Israel Institute of Biological Research (IIBR), Ness-Ziona, IsraelDepartment of Biochemistry and Molecular Genetics, Israel Institute of Biological Research (IIBR), Ness-Ziona, IsraelDepartment of Infectious Diseases, Israel Institute of Biological Research (IIBR), Ness-Ziona, IsraelDepartment of Infectious Diseases, Israel Institute of Biological Research (IIBR), Ness-Ziona, IsraelDepartment of Infectious Diseases, Israel Institute of Biological Research (IIBR), Ness-Ziona, IsraelViral infections of the central nervous system (CNS) lead to a broad range of pathologies. CNS infections with Orthopox viruses have been mainly documented as an adverse reaction to smallpox vaccination with vaccinia virus. To date, there is insufficient data regarding the mechanisms underlying pathological viral replication or viral clearance. Therefore, informed risk assessment of vaccine adverse reactions or outcome prediction is limited. This work applied a model of viral infection of the CNS, comparing neurovirulent with attenuated strains. We followed various parameters along the disease and correlated viral load, morbidity, and mortality with tissue integrity, innate and adaptive immune response and functionality of the blood⁻brain barrier. Combining these data with whole brain RNA-seq analysis performed at different time points indicated that neurovirulence is associated with host immune silencing followed by induction of tissue damage-specific pathways. In contrast, brain infection with attenuated strains resulted in rapid and robust induction of innate and adaptive protective immunity, followed by viral clearance and recovery. This study significantly improves our understanding of the mechanisms and processes determining the consequence of viral CNS infection and highlights potential biomarkers associated with such outcomes.https://www.mdpi.com/2076-393X/7/1/19vacciniabrainmeningoencephalitissmallpoxneurovirulenceRNA-seq |
| spellingShingle | Tomer Israely Nir Paran Noam Erez Lilach Cherry Hadas Tamir Hagit Achdout Boaz Politi Ofir Israeli Galia Zaide Inbar Cohen-Gihon Einat B. Vitner Shlomo Lustig Sharon Melamed Differential Response Following Infection of Mouse CNS with Virulent and Attenuated Vaccinia Virus Strains Vaccines vaccinia brain meningoencephalitis smallpox neurovirulence RNA-seq |
| title | Differential Response Following Infection of Mouse CNS with Virulent and Attenuated Vaccinia Virus Strains |
| title_full | Differential Response Following Infection of Mouse CNS with Virulent and Attenuated Vaccinia Virus Strains |
| title_fullStr | Differential Response Following Infection of Mouse CNS with Virulent and Attenuated Vaccinia Virus Strains |
| title_full_unstemmed | Differential Response Following Infection of Mouse CNS with Virulent and Attenuated Vaccinia Virus Strains |
| title_short | Differential Response Following Infection of Mouse CNS with Virulent and Attenuated Vaccinia Virus Strains |
| title_sort | differential response following infection of mouse cns with virulent and attenuated vaccinia virus strains |
| topic | vaccinia brain meningoencephalitis smallpox neurovirulence RNA-seq |
| url | https://www.mdpi.com/2076-393X/7/1/19 |
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