Infectious Progression of Canine Distemper Virus from Circulating Cerebrospinal Fluid into the Central Nervous System
| Autor: | Fusako Ikeda, Hiroki Sato, Akiko Takenaka, Chieko Kai, Misako Yoneda |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
animal diseases viruses Green Fluorescent Proteins 030106 microbiology Immunology Hippocampal formation Hippocampus Microbiology Virus Cell Line law.invention Measles virus Pathogenesis Mice 03 medical and health sciences Dogs law Cell Line Tumor Virology Chlorocebus aethiops medicine Animals Humans Distemper Distemper Virus Canine Vero Cells Cerebrospinal Fluid Neurons Infectivity biology Canine distemper biology.organism_classification medicine.disease HEK293 Cells 030104 developmental biology Blood-Brain Barrier Cell culture Insect Science Recombinant DNA Receptors Virus Pathogenesis and Immunity Measles |
| Zdroj: | Journal of Virology. 90:9285-9292 |
| ISSN: | 1098-5514 0022-538X |
| Popis: | In the current study, we generated recombinant chimeric canine distemper viruses (CDVs) by replacing the hemagglutinin (H) and/or phosphoprotein (P) gene in an avirulent strain expressing enhanced green fluorescent protein (EGFP) with those of a mouse-adapted neurovirulent strain. An in vitro experimental infection indicated that the chimeric CDVs possessing the H gene derived from the mouse-adapted CDV acquired infectivity for neural cells. These cells lack the CDV receptors that have been identified to date (SLAM and nectin-4), indicating that the H protein defines infectivity in various cell lines. The recombinant viruses were administered intracerebrally to 1-week-old mice. Fatal neurological signs of disease were observed only with a recombinant CDV that possessed both the H and P genes of the mouse-adapted strain, similar to the parental mouse-adapted strain, suggesting that both genes are important to drive virulence of CDV in mice. Using this recombinant CDV, we traced the intracerebral propagation of CDV by detecting EGFP. Widespread infection was observed in the cerebral hemispheres and brainstems of the infected mice. In addition, EGFP fluorescence in the brain slices demonstrated a sequential infectious progression in the central nervous system: CDV primarily infected the neuroependymal cells lining the ventricular wall and the neurons of the hippocampus and cortex adjacent to the ventricle, and it then progressed to an extensive infection of the brain surface, followed by the parenchyma and cortex. In the hippocampal formation, CDV spread in a unidirectional retrograde pattern along neuronal processes in the hippocampal formation from the CA1 region to the CA3 region and the dentate gyrus. Our mouse model demonstrated that the main target cells of CDV are neurons in the acute phase and that the virus spreads via neuronal transmission pathways in the hippocampal formation. IMPORTANCE CDV is the etiological agent of distemper in dogs and other carnivores, and in many respects, the pathogenesis of CDV infection in animals resembles that of measles virus infection in humans. We successfully generated a recombinant CDV containing the H and P genes from a mouse-adapted neurovirulent strain and expressing EGFP. The recombinant CDV exhibited severe neurovirulence with high mortality, comparable to the parental mouse-adapted strain. The mouse-infectious model could become a useful tool for analyzing CDV infection of the central nervous system subsequent to passing through the blood-cerebrospinal fluid barrier and infectious progression in the target cells in acute disease. |
| Databáze: | OpenAIRE |
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