Sphingosine-1-phosphate signaling mediates shedding of measles virus-infected respiratory epithelial cells.

IF 4 2区 医学 Q2 VIROLOGY
Jacqueline K Brockhurst, Brittany E Salciccioli, Diane E Griffin
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引用次数: 0

Abstract

Measles virus (MeV) is an extremely infectious respiratory virus and a major cause of childhood morbidity and mortality worldwide. MeV infection of the respiratory epithelium induces shedding of multinucleate epithelial cells from the apical surface of the epithelium without compromising epithelial barrier integrity. To study the mechanisms driving the apical extrusion of MeV-infected respiratory epithelial cells, we used primary differentiated tracheal epithelial cell cultures (rhTECs) and respiratory samples from rhesus macaques infected with wild-type MeV (WT MeV) or live-attenuated MeV (LAMV). We show that sphingosine-1-phosphate (S1P) signaling, rather than cell death or inflammasome activation, plays a key role in WT MeV and LAMV-induced cell shedding. Inhibiting S1P signaling resulted in delayed shedding of clusters of infected cells and higher viral titers within the epithelium, suggesting that cell extrusion impacts viral dynamics within the respiratory tract. We also found that shedding of individual infected cells began early after apical infection, prior to the formation of infected cell clusters within the epithelium. These findings offer new insights into MeV biology and pathogenesis within the respiratory tract.

Importance: Despite the availability of a safe and effective vaccine, measles virus (MeV) still has a significant global impact, and in 2022 alone led to over 136,000 deaths. MeV is one of the most contagious known viruses and spreads via the respiratory route. When respiratory epithelial cells are infected, they are shed into the lumen of the respiratory tract, but this process is poorly understood. Here, we use primary differentiated respiratory epithelial cells from rhesus macaques to show that sphingosine-1-phosphate (S1P) signaling, and not cell death or inflammasome activation, plays a role in cell shedding during both wild-type and live-attenuated MeV infection. Through this mechanism, MeV-infected cells are extruded without disrupting the integrity of the respiratory epithelium. Inhibiting S1P signaling resulted in delayed shedding of infected cells and higher viral titers in the epithelium. These findings indicate that host cellular responses play an important role in MeV infectivity.

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来源期刊
Journal of Virology
Journal of Virology 医学-病毒学
CiteScore
10.10
自引率
7.40%
发文量
906
审稿时长
1 months
期刊介绍: Journal of Virology (JVI) explores the nature of the viruses of animals, archaea, bacteria, fungi, plants, and protozoa. We welcome papers on virion structure and assembly, viral genome replication and regulation of gene expression, genetic diversity and evolution, virus-cell interactions, cellular responses to infection, transformation and oncogenesis, gene delivery, viral pathogenesis and immunity, and vaccines and antiviral agents.
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