TY - JOUR
T1 - Rhinovirus protease cleavage of nucleoporins
T2 - perspective on implications for airway remodeling
AU - Moorhouse, Jennifer
AU - Val, Nicole
AU - Shahriari, Shadi
AU - Nelson, Michelle
AU - Ashby, Regan
AU - Ghildyal, Reena
N1 - Funding Information:
The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.
Publisher Copyright:
Copyright © 2024 Moorhouse, Val, Shahriari, Nelson, Ashby and Ghildyal.
PY - 2023
Y1 - 2023
N2 - Human Rhinoviruses (RV) are a major cause of common colds and infections in early childhood and can lead to subsequent development of asthma via an as yet unknown mechanism. Asthma is a chronic inflammatory pulmonary disease characterized by significant airway remodeling. A key component of airway remodeling is the transdifferentiation of airway epithelial and fibroblast cells into cells with a more contractile phenotype. Interestingly, transforming growth factor-beta (TGF-β), a well characterized inducer of transdifferentiation, is significantly higher in airways of asthmatics compared to non-asthmatics. RV infection induces TGF-β signaling, at the same time nucleoporins (Nups), including Nup153, are cleaved by RV proteases disrupting nucleocytoplasmic transport. As Nup153 regulates nuclear export of SMAD2, a key intermediate in the TGF-β transdifferentiation pathway, its loss of function would result in nuclear retention of SMAD2 and dysregulated TGF-β signaling. We hypothesize that RV infection leads to increased nuclear SMAD2, resulting in sustained TGF-β induced gene expression, priming the airway for subsequent development of asthma. Our hypothesis brings together disparate studies on RV, asthma and Nup153 with the aim to prompt new research into the role of RV infection in development of asthma.
AB - Human Rhinoviruses (RV) are a major cause of common colds and infections in early childhood and can lead to subsequent development of asthma via an as yet unknown mechanism. Asthma is a chronic inflammatory pulmonary disease characterized by significant airway remodeling. A key component of airway remodeling is the transdifferentiation of airway epithelial and fibroblast cells into cells with a more contractile phenotype. Interestingly, transforming growth factor-beta (TGF-β), a well characterized inducer of transdifferentiation, is significantly higher in airways of asthmatics compared to non-asthmatics. RV infection induces TGF-β signaling, at the same time nucleoporins (Nups), including Nup153, are cleaved by RV proteases disrupting nucleocytoplasmic transport. As Nup153 regulates nuclear export of SMAD2, a key intermediate in the TGF-β transdifferentiation pathway, its loss of function would result in nuclear retention of SMAD2 and dysregulated TGF-β signaling. We hypothesize that RV infection leads to increased nuclear SMAD2, resulting in sustained TGF-β induced gene expression, priming the airway for subsequent development of asthma. Our hypothesis brings together disparate studies on RV, asthma and Nup153 with the aim to prompt new research into the role of RV infection in development of asthma.
KW - airway remodeling
KW - asthma
KW - nucleoporin (Nup) 153
KW - rhinovirus
KW - transdifferentiation
UR - http://www.scopus.com/inward/record.url?scp=85182648268&partnerID=8YFLogxK
U2 - 10.3389/fmicb.2023.1321531
DO - 10.3389/fmicb.2023.1321531
M3 - Article
AN - SCOPUS:85182648268
SN - 1664-302X
VL - 14
SP - 1
EP - 7
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
M1 - 1321531
ER -