Early Target Cells of Measles Virus after Aerosol Infection of Non-Human Primates
| Autor: | Annelies W. Mesman, Martin Ludlow, Bertus K. Rima, Ken Lemon, Rik L. de Swart, Linda J. Rennick, Thijs Kuiken, Teunis B.H. Geijtenbeek, Selma Yüksel, Albert D. M. E. Osterhaus, W. Paul Duprex, Geert van Amerongen, Rory D. de Vries, Stephen McQuaid |
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| Přispěvatelé: | Other departments, AII - Amsterdam institute for Infection and Immunity, Infectious diseases, Faculteit der Geneeskunde, Virology |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Respiratory Medicine/Respiratory Infections
Cell Movement Immunology/Cellular Microbiology and Pathogenesis Lung lcsh:QH301-705.5 Recombination Genetic Inhalation Exposure 0303 health sciences biology 3. Good health medicine.anatomical_structure Lymphatic system Virology/Animal Models of Infection Lymph Research Article lcsh:Immunologic diseases. Allergy Green Fluorescent Proteins Immunology Viremia Microbiology Pathology/Cellular Pathology Virus Measles virus 03 medical and health sciences SDG 3 - Good Health and Well-being Virology Infectious Diseases/Viral Infections Macrophages Alveolar Genetics medicine Animals Molecular Biology 030304 developmental biology Aerosols 030306 microbiology Infectious Diseases/Respiratory Infections Dendritic Cells Virology/Host Invasion and Cell Entry medicine.disease biology.organism_classification Pulmonary Alveoli Disease Models Animal Macaca fascicularis Viral Tropism lcsh:Biology (General) Leukocytes Mononuclear Tissue tropism Parasitology Lymph Nodes lcsh:RC581-607 Viral Fusion Proteins Respiratory tract |
| Zdroj: | PLoS pathogens, 7(1). Public Library of Science PLoS Pathogens, Vol 7, Iss 1, p e1001263 (2011) PLoS Pathogens, 7(1). Public Library of Science PLoS Pathogens (print), 7(1). Public Library of Science PLoS Pathogens |
| ISSN: | 1553-7366 |
| Popis: | Measles virus (MV) is highly infectious, and has long been thought to enter the host by infecting epithelial cells of the respiratory tract. However, epithelial cells do not express signaling lymphocyte activation molecule (CD150), which is the high-affinity cellular receptor for wild-type MV strains. We have generated a new recombinant MV strain expressing enhanced green fluorescent protein (EGFP), based on a wild-type genotype B3 virus isolate from Khartoum, Sudan (KS). Cynomolgus macaques were infected with a high dose of rMVKSEGFP by aerosol inhalation to ensure that the virus could reach the full range of potential target cells throughout the entire respiratory tract. Animals were euthanized 2, 3, 4 or 5 days post-infection (d.p.i., n = 3 per time point) and infected (EGFP+) cells were identified at all four time points, albeit at low levels 2 and 3 d.p.i. At these earliest time points, MV-infected cells were exclusively detected in the lungs by fluorescence microscopy, histopathology and/or virus isolation from broncho-alveolar lavage cells. On 2 d.p.i., EGFP+ cells were phenotypically typed as large mononuclear cells present in the alveolar lumen or lining the alveolar epithelium. One to two days later, larger clusters of MV-infected cells were detected in bronchus-associated lymphoid tissue (BALT) and in the tracheo-bronchial lymph nodes. From 4 d.p.i. onward, MV-infected cells were detected in peripheral blood and various lymphoid tissues. In spite of the possibility for the aerosolized virus to infect cells and lymphoid tissues of the upper respiratory tract, MV-infected cells were not detected in either the tonsils or the adenoids until after onset of viremia. These data strongly suggest that in our model MV entered the host at the alveolar level by infecting macrophages or dendritic cells, which traffic the virus to BALT or regional lymph nodes, resulting in local amplification and subsequent systemic dissemination by viremia. Author Summary Measles remains an important vaccine-preventable cause of morbidity and mortality in developing countries. The causative agent, measles virus (MV), is one of the most contagious viruses known. Measles has an incubation time of approximately two weeks, and surprisingly little is known about the early events after MV infection. Epithelial cells in the upper respiratory tract have long been considered as early target cells, but more recently alveolar macrophages (AM) and dendritic cells (DC) have been proposed as alternatives. We have infected cynomolgus macaques with a high dose of a recombinant EGFP-expressing MV strain via aerosol inhalation, to ensure that the virus had access to the entire respiratory tract. At 2 days post-infection, MV-infected mononuclear cells were detectable in the alveolar lumen but not in the upper respiratory tract. These infected cells migrated through the bronchus-associated lymphoid tissue to the draining tracheo-bronchial lymph node at 3 days post-infection. Systemic infection was initiated from this point, as observed in macaques euthanized 4 or 5 days post-infection. Thus, even though the aerosolized virus had access to epithelial cells and lymphoid tissues along the entire respiratory tract, AM and DC in the lungs were the first cells that sustained MV replication. |
| Databáze: | OpenAIRE |
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