Interferon signaling in the nasal epithelium distinguishes among lethal and common cold respiratory viruses and is critical for viral clearance DOI Creative Commons
Clayton J. Otter, David M. Renner, Alejandra Fausto

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 19, 2023

SUMMARY All respiratory viruses establish primary infections in the nasal epithelium, where efficient innate immune induction may prevent dissemination to lower airway and thus minimize pathogenesis. Human coronaviruses (HCoVs) cause a range of pathologies, but host viral determinants disease during common cold versus lethal HCoV are poorly understood. We model initial site infection using epithelial cells cultured at air-liquid interface (ALI). HCoV-229E, HCoV-NL63 human rhinovirus-16 cold-associated that exhibit unique features this model: early antiviral interferon (IFN) signaling, IFN-mediated clearance, preferential replication temperature (33°C) which confers muted IFN responses. In contrast, SARS-CoV-2 MERS-CoV encode antagonist proteins clearance cultures. Our study identifies shared among viruses, highlighting responses as predictive outcomes nasally-directed IFNs potential therapeutics.

Language: Английский

A Comparison of Conserved Features in the Human Coronavirus Family Shows That Studies of Viruses Less Pathogenic than SARS-CoV-2, Such as HCoV-OC43, Are Good Model Systems for Elucidating Basic Mechanisms of Infection and Replication in Standard Laboratories DOI Creative Commons
Audrey L. Heffner, Tracey A. Rouault

Viruses, Journal Year: 2025, Volume and Issue: 17(2), P. 256 - 256

Published: Feb. 13, 2025

In 2021, at the height of COVID-19 pandemic, coronavirus research spiked, with over 83,000 original articles related to word "coronavirus" added online resource PubMed. Just 2 years later, in 2023, only 30,900 were added. While, irrefutably, funding drastically decreased, a possible explanation for decrease interest is that projects on SARS-CoV-2, causative agent COVID-19, halted due challenge establishing good cellular or animal model system. Most laboratories do not have capabilities culture SARS-CoV-2 'in house' as this requires Biosafety Level (BSL) 3 laboratory. Until recently, BSL laboratory endemic coronaviruses was arduous low cytopathic effect isolated cell infection models and lack means quantify viral loads. The purpose review article compare human provide an assessment latest techniques use coronaviruses-HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1-as lower-biosafety-risk more pathogenic coronaviruses-SARS-CoV-2, SARS-CoV, MERS-CoV.

Language: Английский

Citations

1
Polyoxometalate exerts broad-spectrum activity against human respiratory viruses hampering viral entry. DOI Creative Commons
Irene Arduino, Rachele Francese, Andrea Civra

et al.

Antiviral Research, Journal Year: 2024, Volume and Issue: 226, P. 105897 - 105897

Published: April 27, 2024

Human respiratory viruses have an enormous impact on national health systems, societies, and economy due to the rapid airborne transmission epidemic spread of such pathogens, while effective specific antiviral drugs counteract infections are still lacking. Here, we identified two Keggin-type polyoxometalates (POMs), [TiW11CoO40]8- (TiW11Co) [Ti2PW10O40]7- (Ti2PW10), endowed with broad-spectrum activity against enveloped non-enveloped human viruses, i.e., coronavirus (HCoV-OC43), rhinovirus (HRV-A1), syncytial virus (RSV-A2), adenovirus (AdV-5). Ti2PW10 showed highly favorable selectivity indexes all tested (SIs >700), its potential was further investigated coronaviruses rhinoviruses. This POM found inhibit replication multiple HCoV HRV strains, in different cell systems. did not affect binding or intracellular viral replication, but selectively inhibited entry. Serial passaging presence revealed a high barrier development Ti2PW10-resistant variants HRV-A1 HCoV-OC43. Moreover, able production 3D model nasal epithelium and, importantly, treatment determine cytotoxicity tissue damage. A mucoadhesive thermosensitive situ hydrogel formulation for delivery also developed Ti2PW10. Overall, good biocompatibility lines epithelia, activity, absence resistance reveal as candidate acute diseases, warranting studies identify target/s polyanion assess clinical potential.

Language: Английский

Citations

4
Seasonal human coronaviruses OC43, 229E, and NL63 induce cell surface modulation of entry receptors and display host cell-specific viral replication kinetics DOI Creative Commons

Vinayakumar Siragam,

Mariam Maltseva,

Nicolas Castonguay

et al.

Microbiology Spectrum, Journal Year: 2024, Volume and Issue: 12(7)

Published: June 12, 2024

ABSTRACT The emergence of the COVID-19 pandemic prompted an increased interest in seasonal human coronaviruses. OC43, 229E, NL63, and HKU1 are endemic coronaviruses that cause common cold associated with generally mild respiratory symptoms. In this study, we identified cell lines exhibited cytopathic effects (CPE) upon infection by three these characterized their viral replication kinetics effect on host surface receptor expression. We found NL63 produced CPE LLC-MK2 cells, while OC43 MRC-5, HCT-8, WI-38 lines, 229E MRC-5 day 3 post-infection. observed a sharp increase nucleocapsid spike RNA (vRNA) from to 5 post-infection for all viruses; however, abundance proportion vRNA copies measured supernatants lysates infected cells varied considerably depending virus-host pair. Importantly, modulation coronavirus entry attachment receptors infection. Infection led downregulation CD13 GD3, respectively. contrast, leads ACE2 Attempts block using either soluble or anti-ACE2 monoclonal antibodies demonstrated potential strategies greatly reduce Overall, our results enable better understanding permissive reveal may have implications facilitating co-infections multiple humans. IMPORTANCE Seasonal is important upper tract infections can result complications some individuals. There no vaccines available viruses, only limited antiviral therapeutic options treat most severe cases. A how viruses interact essential identify new prevent infection-related complications. By analyzing different find cell-dependent factors influence genes expressed virus particles released. also analyzed expression be up- down-modulated infecting coronavirus. Our findings raise concerns over possibility enhancement co-infection coronaviruses, which facilitate genetic recombination variants strains.

Language: Английский

Citations

2
Seasonal Human Coronaviruses OC43, 229E, and NL63 Induce Cell Surface Modulation of Entry Receptors and Display Host Cell-Specific Viral Replication Kinetics DOI Creative Commons

Vinayakumar Siragam,

Mariam Maltseva,

Nicolas Castonguay

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 22, 2023

ABSTRACT The emergence of the COVID-19 pandemic prompted increased interest in seasonal human coronaviruses. 229E, OC43, NL63 and HKU1 are endemic coronaviruses that cause common cold associated with generally mild respiratory symptoms. In this study, we identified cell lines exhibited cytopathic effects (CPE) upon infection by three these characterized their viral replication kinetics effect on host surface receptor expression. We found produced CPE LLC-MK2 cells, while OC43 MRC-5, HCT-8 WI-38 lines, 229E MRC-5 day 3 post-infection. observed a sharp increase nucleocapsid spike RNA (vRNA) from to 5 post-infection for all viruses, however abundance proportion vRNAs copies measured supernatants lysates infected cells varied considerably depending virus-host pair. Importantly, modulation coronavirus entry attachment receptors infection. Infection led downregulation CD13 GD3, respectively. contrast, NL63, also lead an ACE2 Attempts block using either soluble or anti-ACE2 monoclonal antibodies demonstrated potential strategies greatly reduce Overall, our results enable better understanding permissive reveal may have implications facilitating co-infections multiple humans. IMPORTANCE Seasonal important upper tract infections can result complications some individuals. There no vaccines available only limited antiviral therapeutic options treat most severe cases. A how viruses interact is essential identify new prevent infection-related complications. By analyzing different find cell-dependent factors influence genes expressed virus particles released. analyzed expression be up down modulated infecting coronavirus. Our findings raise concerns over possibility enhancement co-infection coronaviruses, which facilitate genetic recombination variants strains.

Language: Английский

Citations

0
Interferon signaling in the nasal epithelium distinguishes among lethal and common cold respiratory viruses and is critical for viral clearance DOI Creative Commons
Clayton J. Otter, David M. Renner, Alejandra Fausto

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 19, 2023

SUMMARY All respiratory viruses establish primary infections in the nasal epithelium, where efficient innate immune induction may prevent dissemination to lower airway and thus minimize pathogenesis. Human coronaviruses (HCoVs) cause a range of pathologies, but host viral determinants disease during common cold versus lethal HCoV are poorly understood. We model initial site infection using epithelial cells cultured at air-liquid interface (ALI). HCoV-229E, HCoV-NL63 human rhinovirus-16 cold-associated that exhibit unique features this model: early antiviral interferon (IFN) signaling, IFN-mediated clearance, preferential replication temperature (33°C) which confers muted IFN responses. In contrast, SARS-CoV-2 MERS-CoV encode antagonist proteins clearance cultures. Our study identifies shared among viruses, highlighting responses as predictive outcomes nasally-directed IFNs potential therapeutics.

Language: Английский

Citations

0