title: Early target cells of measles virus after aerosol infection of non-human primates.
abstract: 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 rMV(KS)EGFP 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.
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University of Belfast, Belfast, United Kingdom.
authors.forename: Ken
authors.initials: K
authors.lastname: Lemon
authors.forename: Rory D
authors.initials: RD
authors.lastname: de Vries
authors.forename: Annelies W
authors.initials: AW
authors.lastname: Mesman
authors.forename: Stephen
authors.initials: S
authors.lastname: McQuaid
authors.forename: Geert
authors.initials: G
authors.lastname: van Amerongen
authors.forename: Selma
authors.initials: S
authors.lastname: Yüksel
authors.forename: Martin
authors.initials: M
authors.lastname: Ludlow
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Rennick
authors.forename: Thijs
authors.initials: T
authors.lastname: Kuiken
authors.forename: Bertus K
authors.initials: BK
authors.lastname: Rima
authors.forename: Teunis B H
authors.initials: TB
authors.lastname: Geijtenbeek
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.forename: W Paul
authors.initials: WP
authors.lastname: Duprex
authors.forename: Rik L
authors.initials: RL
authors.lastname: de Swart
mesh_terms: D000336:Aerosols; D000818:Animals; D002465:Cell Movement; D003713:Dendritic Cells / Q000166:cytology / Q000821:virology*; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins; D019570:Inhalation Exposure; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000821:virology*; D008168:Lung; D008198:Lymph Nodes / Q000166:cytology / Q000821:virology; D008252:Macaca fascicularis; D016676:Macrophages, Alveolar / Q000166:cytology / Q000821:virology*; D008459:Measles virus / Q000235:genetics / Q000472:pathogenicity*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000821:virology; D011995:Recombination, Genetic; D014760:Viral Fusion Proteins; D056189:Viral Tropism
chemical_list: D000336:Aerosols; D014760:Viral Fusion Proteins; D049452:Green Fluorescent Proteins