Journal article
Inter-individual Variation in Receptor Expression Influences MERS-CoV Infection and Immune Responses in Airway Epithelia
Frontiers in public health, Vol.9, pp.756049-756049
2021
DOI: 10.3389/fpubh.2021.756049
PMCID: PMC8763803
PMID: 35059374
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) causes respiratory infection in humans, with symptom severity that ranges from asymptomatic to severe pneumonia. Known risk factors for severe MERS include male sex, older age, and the presence of various comorbidities. MERS-CoV gains entry into cells by binding its receptor, dipeptidyl peptidase 4 (DPP4), on the surface of airway epithelia. We hypothesized that expression of this receptor might be an additional determinant of outcomes in different individuals during MERS-CoV infection. To learn more about the role of DPP4 in facilitating MERS-CoV infection and spread, we used ELISA and immunofluorescent staining to characterize DPP4 expression in well-differentiated primary human airway epithelia (HAE). We noted wide inter-individual variation in DPP4 abundance, varying by as much as 1000-fold between HAE donors. This variability appears to influence multiple aspects of MERS-CoV infection and pathogenesis, with greater DPP4 abundance correlating with early, robust virus replication and increased cell sloughing. We also observed increased induction of interferon and some interferon-stimulated genes in response to MERS-CoV infection in epithelia with the greatest DPP4 abundance. Overall, our results indicate that inter-individual differences in DPP4 abundance are one host factor contributing to MERS-CoV replication and host defense responses, and highlight how HAE may serve as a useful model for identifying risk factors associated with heightened susceptibility to serious respiratory pathogens.
Details
- Title: Subtitle
- Inter-individual Variation in Receptor Expression Influences MERS-CoV Infection and Immune Responses in Airway Epithelia
- Creators
- Kun Li - University of IowaChristine Wohlford-Lenane - University of IowaJennifer A Bartlett - University of IowaPaul B McCray Jr - Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA, United States
- Resource Type
- Journal article
- Publication Details
- Frontiers in public health, Vol.9, pp.756049-756049
- DOI
- 10.3389/fpubh.2021.756049
- PMID
- 35059374
- PMCID
- PMC8763803
- NLM abbreviation
- Front Public Health
- ISSN
- 2296-2565
- eISSN
- 2296-2565
- Grant note
- P01 AI060699 / NIAID NIH HHS P30 DK054759 / NIDDK NIH HHS
- Language
- English
- Date published
- 2021
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984297436702771
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