Infection of primary nasal epithelial cells differentiates among lethal and seasonal human coronaviruses

Otter, Clayton J.; Fausto, Alejandra; Tan, Li; Cohen, Noam A.; Weiss, Susan R.

doi:10.1101/2022.10.17.512617

Cited by 10 publications

(21 citation statements)

References 85 publications

(102 reference statements)

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“…The identification and isolation of HCoVs was conducted at 33°C, yielding a recoverable virus (Bucknall et al., 1972; Gorse et al., 2009; Van Der Hoek et al., 2004). We have reported that HCoV‐NL63 and HCoV‐229E are temperature sensitive and their replication is attenuated at 37°C (Otter et al., 2023). This suggests that temperatures warmer than 33°C negatively impact the replication of the HCoVs.…”

Section: Commentarymentioning

confidence: 99%

“…Later, two more HCoVs were identified, HCoV‐NL63 in 2004 and HCoV‐HKU1 the following year (Van Der Hoek et al., 2004; Woo et al., 2005). Of these five HCoVs, SARS‐CoV was the only highly pathogenic HCoV until the emergence of Middle East respiratory syndrome coronavirus (MERS‐CoV) in 2012 and then SARS‐CoV‐2, the causative agent of coronavirus disease 2019 (COVID‐19), in late 2019 (Li et al., 2021; Otter et al., 2023). Unlike SARS‐CoV, MERS‐CoV, and SARS‐CoV‐2, which are associated with severe respiratory disease, HCoV‐229E, ‐OC43, ‐NL63, and ‐HKU1 generally cause mild to moderate upper‐respiratory‐tract disease, though they can also cause more severe disease in at‐risk populations, such as the elderly, the immunocompromised, and young children (Liu et al., 2020).…”

Section: Introductionmentioning

confidence: 99%

“…We have optimized the parameters for the growth of each seasonal HCoV at 33°C, the temperature of the human upper airway, resulting in high viral yields. We have recently reported that infections conducted at 33°C vs. 37°C, reflective of temperatures in the upper and lower airway, revealed that replication of HCoV‐NL63 and ‐229E is significantly attenuated at 37°C (Otter et al., 2023). Additionally, the seasonal HCoVs were isolated at temperatures lower than 37°C (Bucknall et al., 1972; Liu et al., 2020; van der Hoek et al., 2006).…”

Section: Introductionmentioning

confidence: 99%

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Improved Culture Methods for Human Coronaviruses HCoV‐OC43, HCoV‐229E, and HCoV‐NL63

Fausto,

Otter,

Bracci

et al. 2023

Current Protocols

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HCoV‐OC43, HCoV‐229E, HCoV‐NL63, and HCoV‐HKU1 are four of the seven known human coronaviruses (HCoVs) and, unlike the highly pathogenic SARS‐CoV, MERS‐CoV, and SARS‐CoV‐2, these four so‐called seasonal HCoVs generally cause mild upper‐respiratory‐tract illness. As Biosafety Level 2 (BSL‐2) pathogens, the seasonal HCoVs are more accessible and can be used as surrogates for studying the highly pathogenic HCoVs. However, scientists have for many years found these difficult to study because of the lack of a universal culture system and the inability of typical culture methods to yield high‐titer infectious stocks. We have developed assays to grow and quantify infectious virus and viral RNA for HCoV‐OC43, ‐229E, and ‐NL63. We identified which immortalized cell lines should be used to optimize the replication of HCoV‐OC43, ‐229E, and ‐NL63 in order to generate high titers (Vero E6, Huh‐7, and LLC‐MK2 cells, respectively). Here we present protocols for improved propagation and quantification of each seasonal HCoV. © 2023 Wiley Periodicals LLC.Basic Protocol 1: Growth of HCoVsBasic Protocol 2: Quantification of HCoV by plaque assayBasic Protocol 3: Quantification of HCoV RNA products of replicationBasic Protocol 4: Concentrating HCoVs via ultracentrifugation

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Section: Commentarymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Improved Culture Methods for Human Coronaviruses HCoV‐OC43, HCoV‐229E, and HCoV‐NL63

Fausto,

Otter,

Bracci

et al. 2023

Current Protocols

Self Cite

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“…Recent research has compared infectivity of various coronavirus strains in human nasal epithelial cultures, 11 but this study did not provide insight into host transcriptional responses and was limited to the nasal region. Others have compared transcriptional responses to coronavirus infection by combining several independent datasets, 12 or with only a limited number of different coronaviruses 13 .…”

Section: Introductionmentioning

confidence: 99%

SARS‐CoV‐2‐infected human airway epithelial cell cultures uniquely lack interferon and immediate early gene responses caused by other coronaviruses

Wang,

Thaler,

Salgado‐Benvindo

et al. 2024

Clin & Trans Imm

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ObjectivesSevere acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a member of a class of highly pathogenic coronaviruses. The large family of coronaviruses, however, also includes members that cause only mild symptoms, like human coronavirus‐229E (HCoV‐229E) or OC43 (HCoV‐OC43). Unravelling how molecular (and cellular) pathophysiology differs between highly and low pathogenic coronaviruses is important for the development of therapeutic strategies.MethodsHere, we analysed the transcriptome of primary human bronchial epithelial cells (PBEC), differentiated at the air–liquid interface (ALI) after infection with SARS‐CoV‐2, SARS‐CoV, Middle East Respiratory Syndrome (MERS)‐CoV and HCoV‐229E using bulk RNA sequencing.ResultsALI‐PBEC were efficiently infected by all viruses, and SARS‐CoV, MERS‐CoV and HCoV‐229E infection resulted in a largely similar transcriptional response. The response to SARS‐CoV‐2 infection differed markedly as it uniquely lacked the increase in expression of immediate early genes, including FOS, FOSB and NR4A1 that was observed with all other coronaviruses. This finding was further confirmed in publicly available experimental and clinical datasets. Interfering with NR4A1 signalling in Calu‐3 lung epithelial cells resulted in a 100‐fold reduction in extracellular RNA copies of SARS‐CoV‐2 and MERS‐CoV, suggesting an involvement in virus replication. Furthermore, a lack in induction of interferon‐related gene expression characterised the main difference between the highly pathogenic coronaviruses and low pathogenic viruses HCoV‐229E and HCoV‐OC43.ConclusionOur results demonstrate a previously unknown suppression of a host response gene set by SARS‐CoV‐2 and confirm a difference in interferon‐related gene expression between highly pathogenic and low pathogenic coronaviruses.

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“…In particular, OC43, HKU1, 229E, and NL63 are the four most common endemic coronavirus strains with OC43 being the most prevalent in terms of diagnosed cases [3]. Notably, seasonal coronaviruses and influenza viruses are transmitted via an airborne route and can infect the same human respiratory tract tissues including nasal and bronchial epithelial cells [4,5]. Both virus infections can have similar symptoms like cough, fever, and pneumonia and are associated with lower respiratory tract diseases [6].…”

Section: Introductionmentioning

confidence: 99%

Coinfection of Influenza A and B and Human OC43 Coronavirus in Normal Human Bronchial Epithelial Cells

Kim,

Hickerson,

Ilyushina

2024

Influenza Resp Viruses

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BackgroundInfluenza viruses and seasonal coronaviruses are pathogens transmitted via an airborne route that can cause respiratory diseases in humans that have similar symptoms such as fever, cough, and pneumonia. These two viruses can infect similar human tissues, such as the respiratory tract and nasal, bronchial, and alveolar epithelial cells. Influenza virus and seasonal coronavirus coinfections are poorly understood.MethodsHere, we coinfected normal human bronchial epithelial (NHBE) cells with influenza A/California/04/09 (IAV) or B/Victoria/504/2000 (IBV) strains and the seasonal human beta‐coronavirus OC43 and evaluated viral replication capacities. We also examined changes in the expression of various cytokines/chemokines by qPCR and Luminex assay.ResultsWe observed that the replication of IAV and IBV was not affected by coinfection with OC43. However, coinfection reduced OC43 titers (~3‐fold) compared with infection with OC43 alone. Select cytokine/chemokine expression was increased in coinfected cells compared with all single infections with greater differences seen between coinfected cells and cells infected with OC43 alone compared with IAV‐ or IBV‐infected cells. In addition, IL‐8 and IL‐1RA showed the highest expression among a panel of 22 cytokines by Luminex.ConclusionsAs the rate of influenza and seasonal coronavirus coinfection continue to increase, our findings may help set guidelines for the treatments of the individuals coinfected with both viruses.

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Infection of primary nasal epithelial cells differentiates among lethal and seasonal human coronaviruses

Cited by 10 publications

References 85 publications

Improved Culture Methods for Human Coronaviruses HCoV‐OC43, HCoV‐229E, and HCoV‐NL63

Improved Culture Methods for Human Coronaviruses HCoV‐OC43, HCoV‐229E, and HCoV‐NL63

SARS‐CoV‐2‐infected human airway epithelial cell cultures uniquely lack interferon and immediate early gene responses caused by other coronaviruses

Coinfection of Influenza A and B and Human OC43 Coronavirus in Normal Human Bronchial Epithelial Cells

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