tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2023 Apr 11;120(15):e2218083120.
doi: 10.1073/pnas.2218083120. Epub 2023 Apr 6.
Infection of primary nasal epithelial cells differentiates among lethal and seasonal human coronaviruses
Clayton J Otter[SUP] 1 2 [/SUP], Alejandra Fausto[SUP] 1 2 [/SUP], Li Hui Tan[SUP] 3 4 [/SUP], Alisha S Khosla[SUP] 3 4 [/SUP], Noam A Cohen[SUP] 3 4 [/SUP], Susan R Weiss[SUP] 1 2 [/SUP]
Affiliations
Abstract
The nasal epithelium is the initial entry portal and primary barrier to infection by all human coronaviruses (HCoVs). We utilize primary human nasal epithelial cells grown at air-liquid interface, which recapitulate the heterogeneous cellular population as well as mucociliary clearance functions of the in vivo nasal epithelium, to compare lethal [Severe acute respiratory syndrome (SARS)-CoV-2 and Middle East respiratory syndrome-CoV (MERS-CoV)] and seasonal (HCoV-NL63 and HCoV-229E) HCoVs. All four HCoVs replicate productively in nasal cultures, though replication is differentially modulated by temperature. Infections conducted at 33 °C vs. 37 °C (reflective of temperatures in the upper and lower airway, respectively) revealed that replication of both seasonal HCoVs (HCoV-NL63 and -229E) is significantly attenuated at 37 °C. In contrast, SARS-CoV-2 and MERS-CoV replicate at both temperatures, though SARS-CoV-2 replication is enhanced at 33 °C late in infection. These HCoVs also diverge significantly in terms of cytotoxicity induced following infection, as the seasonal HCoVs as well as SARS-CoV-2 cause cellular cytotoxicity as well as epithelial barrier disruption, while MERS-CoV does not. Treatment of nasal cultures with type 2 cytokine IL-13 to mimic asthmatic airways differentially impacts HCoV receptor availability as well as replication. MERS-CoV receptor DPP4 expression increases with IL-13 treatment, whereas ACE2, the receptor used by SARS-CoV-2 and HCoV-NL63, is down-regulated. IL-13 treatment enhances MERS-CoV and HCoV-229E replication but reduces that of SARS-CoV-2 and HCoV-NL63, reflecting the impact of IL-13 on HCoV receptor availability. This study highlights diversity among HCoVs during infection of the nasal epithelium, which is likely to influence downstream infection outcomes such as disease severity and transmissibility.
Keywords: MERS-CoV; NL63; SARS-CoV-2; human coronavirus; nasal epithelium.
. 2023 Apr 11;120(15):e2218083120.
doi: 10.1073/pnas.2218083120. Epub 2023 Apr 6.
Infection of primary nasal epithelial cells differentiates among lethal and seasonal human coronaviruses
Clayton J Otter[SUP] 1 2 [/SUP], Alejandra Fausto[SUP] 1 2 [/SUP], Li Hui Tan[SUP] 3 4 [/SUP], Alisha S Khosla[SUP] 3 4 [/SUP], Noam A Cohen[SUP] 3 4 [/SUP], Susan R Weiss[SUP] 1 2 [/SUP]
Affiliations
- PMID: 37023127
- DOI: 10.1073/pnas.2218083120
Abstract
The nasal epithelium is the initial entry portal and primary barrier to infection by all human coronaviruses (HCoVs). We utilize primary human nasal epithelial cells grown at air-liquid interface, which recapitulate the heterogeneous cellular population as well as mucociliary clearance functions of the in vivo nasal epithelium, to compare lethal [Severe acute respiratory syndrome (SARS)-CoV-2 and Middle East respiratory syndrome-CoV (MERS-CoV)] and seasonal (HCoV-NL63 and HCoV-229E) HCoVs. All four HCoVs replicate productively in nasal cultures, though replication is differentially modulated by temperature. Infections conducted at 33 °C vs. 37 °C (reflective of temperatures in the upper and lower airway, respectively) revealed that replication of both seasonal HCoVs (HCoV-NL63 and -229E) is significantly attenuated at 37 °C. In contrast, SARS-CoV-2 and MERS-CoV replicate at both temperatures, though SARS-CoV-2 replication is enhanced at 33 °C late in infection. These HCoVs also diverge significantly in terms of cytotoxicity induced following infection, as the seasonal HCoVs as well as SARS-CoV-2 cause cellular cytotoxicity as well as epithelial barrier disruption, while MERS-CoV does not. Treatment of nasal cultures with type 2 cytokine IL-13 to mimic asthmatic airways differentially impacts HCoV receptor availability as well as replication. MERS-CoV receptor DPP4 expression increases with IL-13 treatment, whereas ACE2, the receptor used by SARS-CoV-2 and HCoV-NL63, is down-regulated. IL-13 treatment enhances MERS-CoV and HCoV-229E replication but reduces that of SARS-CoV-2 and HCoV-NL63, reflecting the impact of IL-13 on HCoV receptor availability. This study highlights diversity among HCoVs during infection of the nasal epithelium, which is likely to influence downstream infection outcomes such as disease severity and transmissibility.
Keywords: MERS-CoV; NL63; SARS-CoV-2; human coronavirus; nasal epithelium.