Infection of ferrets with wild type-based recombinant canine distemper virus overwhelms the immune system and causes fatal systemic disease
ABSTRACT Canine distemper virus (CDV) causes systemic infection resulting in severe and often fatal disease in a large spectrum of animal host species. The virus is closely related to measles virus and targets myeloid, lymphoid, and epithelial cells, but CDV is more virulent and the infection spread...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-08-01
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| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/msphere.00082-23 |
| _version_ | 1827855255221567488 |
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| author | Brigitta M. Laksono Dagmar Roelofs Anouskha D. Comvalius Katharina S. Schmitz Laurine C. Rijsbergen Daryl Geers Sham Nambulli Peter van Run W. Paul Duprex Judith M. A. van den Brand Rory D. de Vries Rik L. de Swart |
| author_facet | Brigitta M. Laksono Dagmar Roelofs Anouskha D. Comvalius Katharina S. Schmitz Laurine C. Rijsbergen Daryl Geers Sham Nambulli Peter van Run W. Paul Duprex Judith M. A. van den Brand Rory D. de Vries Rik L. de Swart |
| author_sort | Brigitta M. Laksono |
| collection | DOAJ |
| description | ABSTRACT Canine distemper virus (CDV) causes systemic infection resulting in severe and often fatal disease in a large spectrum of animal host species. The virus is closely related to measles virus and targets myeloid, lymphoid, and epithelial cells, but CDV is more virulent and the infection spreads more rapidly within the infected host. Here, we aimed to study the pathogenesis of wild-type CDV infection by experimentally inoculating ferrets with recombinant CDV (rCDV) based on an isolate directly obtained from a naturally infected raccoon. The recombinant virus was engineered to express a fluorescent reporter protein, facilitating assessment of viral tropism and virulence. In ferrets, this wild type-based rCDV infected myeloid, lymphoid, and epithelial cells, and the infection resulted in systemic dissemination to multiple tissues and organs, especially those of the lymphatic system. High infection percentages in immune cells resulted in depletion of these cells both from circulation and from lymphoid tissues. The majority of CDV-infected ferrets reached their humane endpoints within 20 d and had to be euthanized. In that period, the virus also reached the central nervous system in several ferrets, but we did not observe the development of neurological complications during the study period of 23 d. Two out of 14 ferrets survived CDV infection and developed neutralizing antibodies. We show for the first time the pathogenesis of a non-adapted wild type-based rCDV in ferrets. IMPORTANCE Infection of ferrets with recombinant canine distemper virus (rCDV) expressing a fluorescent reporter protein has been used as proxy to understand measles pathogenesis and immune suppression in humans. CDV and measles virus use the same cellular receptors, but CDV is more virulent, and infection is often associated with neurological complications. rCDV strains in current use have complicated passage histories, which may have affected their pathogenesis. Here, we studied the pathogenesis of the first wild type-based rCDV in ferrets. We used macroscopic fluorescence to identify infected cells and tissues; multicolor flow cytometry to determine viral tropism in immune cells; and histopathology and immunohistochemistry to characterize infected cells and lesions in tissues. We conclude that CDV often overwhelmed the immune system, resulting in viral dissemination to multiple tissues in the absence of a detectable neutralizing antibody response. This virus is a promising tool to study the pathogenesis of morbillivirus infections. |
| first_indexed | 2024-03-12T11:42:28Z |
| format | Article |
| id | doaj.art-4bda23daf9864f099be972878bb93daa |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-03-12T11:42:28Z |
| publishDate | 2023-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-4bda23daf9864f099be972878bb93daa2023-08-31T14:26:41ZengAmerican Society for MicrobiologymSphere2379-50422023-08-018410.1128/msphere.00082-23Infection of ferrets with wild type-based recombinant canine distemper virus overwhelms the immune system and causes fatal systemic diseaseBrigitta M. Laksono0Dagmar Roelofs1Anouskha D. Comvalius2Katharina S. Schmitz3Laurine C. Rijsbergen4Daryl Geers5Sham Nambulli6Peter van Run7W. Paul Duprex8Judith M. A. van den Brand9Rory D. de Vries10Rik L. de Swart11Department of Viroscience, Erasmus MC , Rotterdam, the NetherlandsDepartment of Biomolecular Health Sciences, Division of Pathology, Universiteit Utrecht , Utrecht, the NetherlandsDepartment of Viroscience, Erasmus MC , Rotterdam, the NetherlandsDepartment of Viroscience, Erasmus MC , Rotterdam, the NetherlandsDepartment of Viroscience, Erasmus MC , Rotterdam, the NetherlandsDepartment of Viroscience, Erasmus MC , Rotterdam, the NetherlandsCentre for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania, USADepartment of Viroscience, Erasmus MC , Rotterdam, the NetherlandsCentre for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania, USADepartment of Biomolecular Health Sciences, Division of Pathology, Universiteit Utrecht , Utrecht, the NetherlandsDepartment of Viroscience, Erasmus MC , Rotterdam, the NetherlandsDepartment of Viroscience, Erasmus MC , Rotterdam, the NetherlandsABSTRACT Canine distemper virus (CDV) causes systemic infection resulting in severe and often fatal disease in a large spectrum of animal host species. The virus is closely related to measles virus and targets myeloid, lymphoid, and epithelial cells, but CDV is more virulent and the infection spreads more rapidly within the infected host. Here, we aimed to study the pathogenesis of wild-type CDV infection by experimentally inoculating ferrets with recombinant CDV (rCDV) based on an isolate directly obtained from a naturally infected raccoon. The recombinant virus was engineered to express a fluorescent reporter protein, facilitating assessment of viral tropism and virulence. In ferrets, this wild type-based rCDV infected myeloid, lymphoid, and epithelial cells, and the infection resulted in systemic dissemination to multiple tissues and organs, especially those of the lymphatic system. High infection percentages in immune cells resulted in depletion of these cells both from circulation and from lymphoid tissues. The majority of CDV-infected ferrets reached their humane endpoints within 20 d and had to be euthanized. In that period, the virus also reached the central nervous system in several ferrets, but we did not observe the development of neurological complications during the study period of 23 d. Two out of 14 ferrets survived CDV infection and developed neutralizing antibodies. We show for the first time the pathogenesis of a non-adapted wild type-based rCDV in ferrets. IMPORTANCE Infection of ferrets with recombinant canine distemper virus (rCDV) expressing a fluorescent reporter protein has been used as proxy to understand measles pathogenesis and immune suppression in humans. CDV and measles virus use the same cellular receptors, but CDV is more virulent, and infection is often associated with neurological complications. rCDV strains in current use have complicated passage histories, which may have affected their pathogenesis. Here, we studied the pathogenesis of the first wild type-based rCDV in ferrets. We used macroscopic fluorescence to identify infected cells and tissues; multicolor flow cytometry to determine viral tropism in immune cells; and histopathology and immunohistochemistry to characterize infected cells and lesions in tissues. We conclude that CDV often overwhelmed the immune system, resulting in viral dissemination to multiple tissues in the absence of a detectable neutralizing antibody response. This virus is a promising tool to study the pathogenesis of morbillivirus infections.https://journals.asm.org/doi/10.1128/msphere.00082-23morbilliviruscanine distemper virusimmunopathogenesisferrets |
| spellingShingle | Brigitta M. Laksono Dagmar Roelofs Anouskha D. Comvalius Katharina S. Schmitz Laurine C. Rijsbergen Daryl Geers Sham Nambulli Peter van Run W. Paul Duprex Judith M. A. van den Brand Rory D. de Vries Rik L. de Swart Infection of ferrets with wild type-based recombinant canine distemper virus overwhelms the immune system and causes fatal systemic disease mSphere morbillivirus canine distemper virus immunopathogenesis ferrets |
| title | Infection of ferrets with wild type-based recombinant canine distemper virus overwhelms the immune system and causes fatal systemic disease |
| title_full | Infection of ferrets with wild type-based recombinant canine distemper virus overwhelms the immune system and causes fatal systemic disease |
| title_fullStr | Infection of ferrets with wild type-based recombinant canine distemper virus overwhelms the immune system and causes fatal systemic disease |
| title_full_unstemmed | Infection of ferrets with wild type-based recombinant canine distemper virus overwhelms the immune system and causes fatal systemic disease |
| title_short | Infection of ferrets with wild type-based recombinant canine distemper virus overwhelms the immune system and causes fatal systemic disease |
| title_sort | infection of ferrets with wild type based recombinant canine distemper virus overwhelms the immune system and causes fatal systemic disease |
| topic | morbillivirus canine distemper virus immunopathogenesis ferrets |
| url | https://journals.asm.org/doi/10.1128/msphere.00082-23 |
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