Journal article
Epithelial-to-mesenchymal transition and live cell extrusion contribute to measles virus release from human airway epithelia
Journal of virology, Vol.99(2), e01220-24
02/25/2025
DOI: 10.1128/jvi.01220-24
PMCID: PMC11852777
PMID: 39791903
Abstract
Measles virus (MeV) is a highly contagious respiratory virus transmitted via aerosols. To understand how MeV exits the airways of an infected host, we use unpassaged primary cultures of human airway epithelial cells (HAE). MeV typically remains cell-associated in HAE and forms foci of infection, termed infectious centers, by directly spreading cell-to-cell. We previously described the phenomenon in which infectious centers detach
from HAE and remain viable. Here, we investigate the mechanism of this cellular detachment. Via immunostaining, we observed loss of tight junction and cell adhesion proteins within infectious centers. These morphological changes indicate activation of epithelial-to-mesenchymal transition (EMT). EMT can contribute to wound healing in respiratory epithelia by mobilizing nearby cells. Inhibiting TGF-β, and thus EMT, reduced infectious center detachment. Compared with uninfected cells, MeV-infected cells also expressed increased levels of sphingosine kinase 1 (SK1), a regulator of live cell extrusion. Live cell extrusion encourages cells to detach from respiratory epithelia by contracting the actomyosin of neighboring cells. Inhibition or induction of live cell extrusion impacted infectious center detachment rates. Thus, these two related pathways contributed to infectious center detachment in HAE. Detached infectious centers contained high titers of virus that may be protected from the environment, allowing the virus to live on surfaces longer and infect more hosts.IMPORTANCEMeasles virus (MeV) is an extremely contagious respiratory pathogen that continues to cause large, disruptive outbreaks each year. Here, we examine mechanisms of detachment of MeV-infected cells. MeV spreads cell-to-cell in human airway epithelial cells (HAE) to form groups of infected cells, termed "infectious centers". We reported that infectious centers ultimately detach from HAE as a unit, carrying high titers of virus. Viral particles within cells may be more protected from environmental conditions, such as ultraviolet radiation and desiccation. We identified two host pathways, epithelial-to-mesenchymal transition and live cell extrusion, that contribute to infectious center detachment. Perturbing these pathways altered the kinetics of infectious center detachment. These pathways influence one another and contribute to epithelial wound healing, suggesting that infectious center detachment may be a usurped consequence of the host's response to infection that benefits MeV by increasing its transmissibility between hosts.
Details
- Title: Subtitle
- Epithelial-to-mesenchymal transition and live cell extrusion contribute to measles virus release from human airway epithelia
- Creators
- Camilla E Hippee - University of IowaLorellin A Durnell - University of IowaJustin W Kaufman - University of IowaEileen Murray - University of IowaBrajesh K Singh - University of IowaPatrick L Sinn - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.99(2), e01220-24
- DOI
- 10.1128/jvi.01220-24
- PMID
- 39791903
- PMCID
- PMC11852777
- NLM abbreviation
- J Virol
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Publisher
- AMER SOC MICROBIOLOGY; WASHINGTON
- Grant note
- HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)Genomics Division of the Iowa Institute of Human Genetics
We thank Roberto Cattaneo for providing fluorescent MeVs and guidance. Additionally, we thank Jennifer Bartlett for her thoughtful review of this manuscript. We acknowledge the support of the University of Iowa Central Microscopy Research Facility, the Genomics Division of the Iowa Institute of Human Genetics, and the In Vitro Models and Cell Culture Core.
- Language
- English
- Electronic publication date
- 01/10/2025
- Date published
- 02/25/2025
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics
- Record Identifier
- 9984772246902771
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