Variable DPP4 expression in multiciliated cells of the human nasal epithelium as a determinant for MERS-CoV tropism

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(11)

Published: March 6, 2025

Transmissibility of respiratory viruses is a complex viral trait that intricately linked to tropism. Several highly transmissible viruses, including severe acute syndrome coronavirus 2 and Influenza specifically target multiciliated cells in the upper tract facilitate efficient human-to-human transmission. In contrast, zoonotic Middle East (MERS-CoV) generally transmits poorly between humans, which largely attributed absence its receptor dipeptidyl peptidase 4 (DPP4) tract. At same time, MERS-CoV epidemiology characterized by occasional superspreading events, suggesting some individuals can disseminate this virus effectively. Here, we utilized well-differentiated human pulmonary nasal airway organoid-derived cultures further delineate tropism MERS-CoV. We find replicated high titers both cultures. Using single-cell messenger-RNA sequencing, immunofluorescence, immunohistochemistry, show preferentially targeted cells, leading loss ciliary coverage. cellular was dependent on differentiation cultures, replication efficiency varied considerably donors. Similarly, variable focal expression DPP4 revealed nose tissues. This study indicates may vary due differences expression, providing an explanation for unpredictable transmission pattern

Language: Английский

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Anti-interferon armamentarium of human coronaviruses

Cellular and Molecular Life Sciences, Journal Year: 2025, Volume and Issue: 82(1)

Published: March 13, 2025

Abstract Cellular innate immune pathways are formidable barriers against viral invasion, creating an environment unfavorable for virus replication. Interferons (IFNs) play a crucial role in driving and regulating these cell-intrinsic antiviral mechanisms through the action of interferon-stimulated genes (ISGs). The host IFN response obstructs replication at every stage, prompting viruses to evolve various strategies counteract or evade this response. Understanding interplay between proteins IFN-mediated is essential developing anti-inflammatory strategies. Human coronaviruses (HCoVs), including SARS-CoV-2, MERS-CoV, SARS-CoV, seasonal coronaviruses, encode range that, shared distinct mechanisms, inhibit responses. Compounding issue, dysregulated early can lead hyper-inflammatory reaction later infection, resulting severe disease. This review provides brief overview HCoV detailed account its interaction with cellular regulated by IFN.

Language: Английский

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Expanding the bat toolbox: Carollia perspicillata bat cell lines and reagents enable the characterization of viral susceptibility and innate immune responses

PLoS Biology, Journal Year: 2025, Volume and Issue: 23(4), P. e3003098 - e3003098

Published: April 15, 2025

Multiple viruses that are highly pathogenic in humans known to have evolved bats. How bats tolerate infection with these viruses, however, is poorly understood. As engage a wide range of interactions their hosts, it essential study bat system resembles natural environment like bat-derived vitro cellular models. However, stable and accessible cell lines not widely available for the broader scientific community. Here, we generated reagents Seba’s short-tailed ( Carollia perspicillata ), tested multiple methods immortalization, characterized susceptibility virus response immune stimulation. Using pseudotyped library authentic infections, show C. derived from diverse array tissues susceptible bearing glycoprotein numerous orthohantaviruses, including Andes Hantaan also live hantavirus infection. Furthermore, stimulation synthetic double-stranded RNA prior vesicular stomatitis Middle Eastern respiratory syndrome coronavirus induced protective antiviral response, demonstrating suitability our response. Taken together, approaches outlined here will inform future efforts develop tools virology non-model organisms enable studies on virus–host

Language: Английский

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Human coronaviruses: activation and antagonism of innate immune responses

Microbiology and Molecular Biology Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 19, 2024

SUMMARY Human coronaviruses cause a range of respiratory diseases, from the common cold (HCoV-229E, HCoV-NL63, HCoV-OC43, and SARS-CoV-2) to lethal pneumonia (SARS-CoV, SARS-CoV-2, MERS-CoV). Coronavirus interactions with host innate immune antiviral responses are an important determinant disease outcome. This review compares host’s response different human coronaviruses. Host defenses discussed in this include frontline against viruses nasal epithelium, early sensing viral infection by effectors, double-stranded RNA stress-induced pathways, antagonism conferred conserved coronavirus nonstructural proteins genus-specific accessory proteins. The HCoV-229E -NL63 induce robust interferon signaling related SARS-CoV SARS-CoV-2 intermediate levels activation, MERS-CoV shuts down these pathways almost completely.

Language: Английский

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The Unusual Role of Ribonuclease L in Innate Immunity

Wiley Interdisciplinary Reviews - RNA, Journal Year: 2024, Volume and Issue: 15(6)

Published: Nov. 1, 2024

ABSTRACT Ribonuclease L is an endonuclease that activated as part of the dsRNA‐driven innate immune response. Active RNase cleaves pathogenic RNAs a way to eliminate infections. However, there are additional and unexpected ways causes changes in host promote response contribute its role defense. Central these unconventional mechanisms observation also degrades mRNA host. In turn, fragments generates can be translated. This activation ribosome collision sensor leads downstream signaling cell death. Additionally, liberation RNA binding proteins after decay appears affect gene expression. this review, we discuss other recent advances focus on novel unusual contributes immunity.

Language: Английский

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