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. 2020 Dec;63(6):859-863.
doi: 10.1165/rcmb.2020-0394LE.

Effects of Asthma and Human Rhinovirus A16 on the Expression of SARS-CoV-2 Entry Factors in Human Airway Epithelium

Ryan C Murphy  1 , Ying Lai  1 , Kaitlyn A Barrow  2 , Jessica A Hamerman  3 , Adam Lacy-Hulbert  3 , Adrian M Piliponsky  2 , Steven F Ziegler  3 , William A Altemeier  1 , Jason S Debley  2   4 , Sina A Gharib  1 , Teal S Hallstrand  1
Affiliations

Effects of Asthma and Human Rhinovirus A16 on the Expression of SARS-CoV-2 Entry Factors in Human Airway Epithelium

Ryan C Murphy et al. Am J Respir Cell Mol Biol. 2020 Dec.
No abstract available

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Figures

Figure 1.
Figure 1.
Epithelial brushings were obtained via bronchoscopy from the fourth- and fifth- generation airways from a cohort of individuals with and without asthma, and for those with asthma, with and without exercise-induced bronchoconstriction (EIB) (control, n = 3; EIB−, n = 9; EIB+, n = 11). (A and C) ACE2 (angiotensin-converting enzyme 2) expression (A) and TMPRSS2 expression (C) were quantified by normalized log2 counts. Median values with interquartile ranges are shown. P values represent the result of a one-way ANOVA. There was a trend toward correlation between ACE2 expression and indirect or endogenous airway hyperresponsiveness as determined by the severity of EIB, defined by the area under the forced expiratory volume in 1 second (FEV1) versus 30 minutes postexercise challenge time curve (B). (D) TMPRSS2 expression correlated with baseline FEV1. Linear regression lines are shown with the 95% confidence intervals as dotted lines. AUC30 = 30 minutes postexercise challenge time curve; TMPRSS2 = transmembrane serine protease 2.
Figure 2.
Figure 2.
(A and D) RNA sequencing was performed on airway epithelial cells (AECs) obtained via blind bronchial epithelial brushings from intubated pediatric study subjects (healthy control subjects [HC], subjects with asthma [A], and all subjects [All]) and differentiated in organotypic cultures. ACE2 expression (A) and TMPRSS2 expression (D) were quantified by normalized log2 counts both at baseline and after infection with human rhinovirus-A16 (HRV-A16) at 48 hours. Median values with interquartile ranges are shown. P values comparing HC to A ± HRV-A16 represent the results of a two-way ANOVA. P values comparing All ± HRV-A16 represent the results of paired t tests. (B and E) PCR analysis was performed on nondiseased lung transplant donor AECs differentiated in air–liquid interface organotypic cultures and exposed to HRV-A16. ACE2 (B) and TMPRSS2 (E) expression levels in comparison with the housekeeping gene HPRT were assessed at various time points after infection (n = 4, each data point represents the mean of two PCR reactions). Mean values are shown with error bars representing the SE of the mean. P values represent the result of one-way ANOVA. (C and F) PCR analysis was performed on AECs from healthy control pediatric study subjects who were stimulated with IFNβ1 (1 ng/ml) and IFNλ2 (1 ng/ml) for 72 hours. ACE2 (C) and TMPRSS2 (F) expression levels in comparison with the housekeeping gene GAPDH (n = 4, each data point represents the mean of three PCR reactions) are shown. Mean values are shown with error bars representing the SE of the mean. The P value in C is the result of a one-way ANOVA. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001. Ctrl = control; HPRT = hypoxanthine guanine phosphoribosyltransferase.
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