title: Infection of lymphoid tissues in the macaque upper respiratory tract contributes to the emergence of transmissible measles virus.
abstract: Measles virus (MV), a member of the family Paramyxoviridae, remains a major cause of morbidity and mortality in the developing world. MV is spread by aerosols but the mechanism(s) responsible for the high transmissibility of MV are largely unknown. We previously infected macaques with enhanced green fluorescent protein-expressing recombinant MV and euthanized them at a range of time points. In this study a comprehensive pathological analysis has been performed of tissues from the respiratory tract around the peak of virus replication. Isolation of virus from nose and throat swab samples showed that high levels of both cell-associated and cell-free virus were present in the upper respiratory tract. Analysis of tissue sections from lung and primary bronchus revealed localized infection of epithelial cells, concomitant infiltration of MV-infected immune cells into the epithelium and localized shedding of cells or cell debris into the lumen. While high numbers of MV-infected cells were present in the tongue, these were largely encapsulated by intact keratinocyte cell layers that likely limit virus transmission. In contrast, the integrity of tonsillar and adenoidal epithelia was disrupted with high numbers of MV-infected epithelial cells and infiltrating immune cells present throughout epithelial cell layers. Disruption was associated with large numbers of MV-infected cells or cell debris 'spilling' from epithelia into the respiratory tract. The coughing and sneezing response induced by disruption of the ciliated epithelium, leading to the expulsion of MV-infected cells, cell debris and cell-free virus, contributes to the highly infectious nature of MV.
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Ludlow
authors.affiliation: Department Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Rory D
authors.initials: RD
authors.lastname: de Vries
authors.affiliation: School of Medicine, Dentistry and Biomedical Sciences, Queen's University of Belfast, Belfast, Northern Ireland, UK.
authors.forename: Ken
authors.initials: K
authors.lastname: Lemon
authors.affiliation: Tissue Pathology Laboratories, Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.|School of Medicine, Dentistry and Biomedical Sciences, Queen's University of Belfast, Belfast, Northern Ireland, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: McQuaid
authors.affiliation: School of Medicine, Dentistry and Biomedical Sciences, Queen's University of Belfast, Belfast, Northern Ireland, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Millar
authors.affiliation: Department Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: van Amerongen
authors.affiliation: Department Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Selma
authors.initials: S
authors.lastname: Yüksel
authors.affiliation: Department Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: R Joyce
authors.initials: RJ
authors.lastname: Verburgh
authors.affiliation: Department Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Albert D M E
authors.initials: ADME
authors.lastname: Osterhaus
authors.affiliation: Department Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Rik L
authors.initials: RL
authors.lastname: de Swart
authors.affiliation: School of Medicine, Dentistry and Biomedical Sciences, Queen's University of Belfast, Belfast, Northern Ireland, UK.|Department of Microbiology, Boston University School of Medicine, Boston, MA, USA.
authors.forename: W Paul
authors.initials: WP
authors.lastname: Duprex
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008221:Lymphoid Tissue / Q000821:virology; D008251:Macaca; D008457:Measles / Q000473:pathology / Q000821:virology*; D008459:Measles virus / Q000302:isolation & purification / Q000472:pathogenicity*; D020545:Respiratory Mucosa / Q000821:virology; D012137:Respiratory System / Q000473:pathology / Q000821:virology; D012141:Respiratory Tract Infections / Q000473:pathology / Q000821:virology*; D019562:Viral Load