A Mouse Model of PPRV Infection for Elucidating Protective and Pathological Roles of Immune Cells
The study was aimed at developing an accessible laboratory animal model to elucidate protective and pathological roles of immune mediators during Peste des petits ruminants virus (PPRV) infection. It is because of the critical roles of type I IFNs in anti-viral defense, we assessed the susceptibilit...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.630307/full |
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| author | Yashu Sharma Roman Sarkar Ayush Jain Sudhakar Singh Chander Shekhar Chandrasekar Shanmugam Muthuchelvan Dhanavelu Prabhakar Tembhurne Rajeev Kaul Sharvan Sehrawat |
| author_facet | Yashu Sharma Roman Sarkar Ayush Jain Sudhakar Singh Chander Shekhar Chandrasekar Shanmugam Muthuchelvan Dhanavelu Prabhakar Tembhurne Rajeev Kaul Sharvan Sehrawat |
| author_sort | Yashu Sharma |
| collection | DOAJ |
| description | The study was aimed at developing an accessible laboratory animal model to elucidate protective and pathological roles of immune mediators during Peste des petits ruminants virus (PPRV) infection. It is because of the critical roles of type I IFNs in anti-viral defense, we assessed the susceptibility of IFN receptor knock out (IFNR KO) mice to PPRV infection. IFNR KO mice were exceedingly susceptible to the infection but WT animals efficiently controlled PPRV. Accordingly, the PPRV infected IFNR KO mice gradually reduced their body weights and succumbed to the infection within 10 days irrespective of the dose and route of infection. The lower infecting doses predominantly induced immunopathological lesions. The viral antigens as well as the replicating PPRV were abundantly present in most of the critical organs such as brain, lungs, heart and kidneys of IFNR KO mice infected with high dose of the virus. Neutrophils and macrophages transported the replicating virus to central nervous system (CNS) and contributed to pathology while the elevated NK and T cell responses directly correlated with the resolution of PPRV infection in WT animals. Using an array of fluorescently labeled H-2Kb tetramers, we discovered four immunogenic epitopes of PPRV. The PPRV-peptides interacted well with H-2Kb in acellular and cellular assay as well as expanded the virus-specific CD8+ T cells in immunized or infected mice. Adoptively transferred CD8+ T cells helped control PPRV in infected mice. Our study therefore established and employed a mouse model for investigating the pathogenesis of PPRV. The model could be useful for elucidating the contribution of immune cells in disease progression as well as to test anti-viral agents. |
| first_indexed | 2024-12-14T16:51:16Z |
| format | Article |
| id | doaj.art-4d2afdc305974cdda651db994d504710 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T16:51:16Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4d2afdc305974cdda651db994d5047102022-12-21T22:54:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-04-011210.3389/fimmu.2021.630307630307A Mouse Model of PPRV Infection for Elucidating Protective and Pathological Roles of Immune CellsYashu Sharma0Roman Sarkar1Ayush Jain2Sudhakar Singh3Chander Shekhar4Chandrasekar Shanmugam5Muthuchelvan Dhanavelu6Prabhakar Tembhurne7Rajeev Kaul8Sharvan Sehrawat9Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Mohali, IndiaDepartment of Biological Sciences, Indian Institute of Science Education and Research Mohali, Mohali, IndiaDepartment of Biological Sciences, Indian Institute of Science Education and Research Mohali, Mohali, IndiaDepartment of Biological Sciences, Indian Institute of Science Education and Research Mohali, Mohali, IndiaDepartment of Biological Sciences, Indian Institute of Science Education and Research Mohali, Mohali, IndiaDivision of Virology, Indian Veterinary Research Institute, Mukteshwar, IndiaDivision of Virology, Indian Veterinary Research Institute, Mukteshwar, IndiaDepartment of Veterinary Microbiology, Nagpur Veterinary College, Nagpur, IndiaDepartment of Microbiology, University of Delhi, New Delhi, IndiaDepartment of Biological Sciences, Indian Institute of Science Education and Research Mohali, Mohali, IndiaThe study was aimed at developing an accessible laboratory animal model to elucidate protective and pathological roles of immune mediators during Peste des petits ruminants virus (PPRV) infection. It is because of the critical roles of type I IFNs in anti-viral defense, we assessed the susceptibility of IFN receptor knock out (IFNR KO) mice to PPRV infection. IFNR KO mice were exceedingly susceptible to the infection but WT animals efficiently controlled PPRV. Accordingly, the PPRV infected IFNR KO mice gradually reduced their body weights and succumbed to the infection within 10 days irrespective of the dose and route of infection. The lower infecting doses predominantly induced immunopathological lesions. The viral antigens as well as the replicating PPRV were abundantly present in most of the critical organs such as brain, lungs, heart and kidneys of IFNR KO mice infected with high dose of the virus. Neutrophils and macrophages transported the replicating virus to central nervous system (CNS) and contributed to pathology while the elevated NK and T cell responses directly correlated with the resolution of PPRV infection in WT animals. Using an array of fluorescently labeled H-2Kb tetramers, we discovered four immunogenic epitopes of PPRV. The PPRV-peptides interacted well with H-2Kb in acellular and cellular assay as well as expanded the virus-specific CD8+ T cells in immunized or infected mice. Adoptively transferred CD8+ T cells helped control PPRV in infected mice. Our study therefore established and employed a mouse model for investigating the pathogenesis of PPRV. The model could be useful for elucidating the contribution of immune cells in disease progression as well as to test anti-viral agents.https://www.frontiersin.org/articles/10.3389/fimmu.2021.630307/fullpeste des petits ruminants virusCD8 T cellsmouse modelclass I epitopespathogenicityIFNR KO |
| spellingShingle | Yashu Sharma Roman Sarkar Ayush Jain Sudhakar Singh Chander Shekhar Chandrasekar Shanmugam Muthuchelvan Dhanavelu Prabhakar Tembhurne Rajeev Kaul Sharvan Sehrawat A Mouse Model of PPRV Infection for Elucidating Protective and Pathological Roles of Immune Cells Frontiers in Immunology peste des petits ruminants virus CD8 T cells mouse model class I epitopes pathogenicity IFNR KO |
| title | A Mouse Model of PPRV Infection for Elucidating Protective and Pathological Roles of Immune Cells |
| title_full | A Mouse Model of PPRV Infection for Elucidating Protective and Pathological Roles of Immune Cells |
| title_fullStr | A Mouse Model of PPRV Infection for Elucidating Protective and Pathological Roles of Immune Cells |
| title_full_unstemmed | A Mouse Model of PPRV Infection for Elucidating Protective and Pathological Roles of Immune Cells |
| title_short | A Mouse Model of PPRV Infection for Elucidating Protective and Pathological Roles of Immune Cells |
| title_sort | mouse model of pprv infection for elucidating protective and pathological roles of immune cells |
| topic | peste des petits ruminants virus CD8 T cells mouse model class I epitopes pathogenicity IFNR KO |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.630307/full |
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