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Infection of ferrets with wild type-based recombinant canine distemper virus overwhelms the immune system and causes fatal systemic disease.
Laksono, Brigitta M; Roelofs, Dagmar; Comvalius, Anouskha D; Schmitz, Katharina S; Rijsbergen, Laurine C; Geers, Daryl; Nambulli, Sham; van Run, Peter; Duprex, W Paul; van den Brand, Judith M A; de Vries, Rory D; de Swart, Rik L.
Afiliação
  • Laksono BM; Department of Viroscience, Erasmus MC , Rotterdam, the Netherlands.
  • Roelofs D; Department of Biomolecular Health Sciences, Division of Pathology, Universiteit Utrecht , Utrecht, the Netherlands.
  • Comvalius AD; Department of Viroscience, Erasmus MC , Rotterdam, the Netherlands.
  • Schmitz KS; Department of Viroscience, Erasmus MC , Rotterdam, the Netherlands.
  • Rijsbergen LC; Department of Viroscience, Erasmus MC , Rotterdam, the Netherlands.
  • Geers D; Department of Viroscience, Erasmus MC , Rotterdam, the Netherlands.
  • Nambulli S; Centre for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania, USA.
  • van Run P; Department of Viroscience, Erasmus MC , Rotterdam, the Netherlands.
  • Duprex WP; Centre for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania, USA.
  • van den Brand JMA; Department of Biomolecular Health Sciences, Division of Pathology, Universiteit Utrecht , Utrecht, the Netherlands.
  • de Vries RD; Department of Viroscience, Erasmus MC , Rotterdam, the Netherlands.
  • de Swart RL; Department of Viroscience, Erasmus MC , Rotterdam, the Netherlands.
mSphere ; 8(4): e0008223, 2023 08 24.
Article em En | MEDLINE | ID: mdl-37377421
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cinomose / Vírus da Cinomose Canina Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cinomose / Vírus da Cinomose Canina Idioma: En Ano de publicação: 2023 Tipo de documento: Article