scholarly journals Cigarette smoke preferentially induces full length ACE2 exposure in primary human airway cells but does not alter susceptibility to SARS-CoV-2 infection

2021 ◽  
Author(s):  
Linsey M Porter ◽  
Wenrui Guo ◽  
Thomas WM Crozier ◽  
Edward JD Greenwood ◽  
Brian Ortmann ◽  
...  
Keyword(s):  
Cigarette Smoking ◽  
Cigarette Smoke ◽  
Type I Interferon ◽  
Epidemiological Data ◽  
Excess Risk ◽  
Full Length ◽  
Type I ◽  
Human Airway ◽  
Air Liquid Interface ◽  
Airway Cells

AbstractCigarette smoking has multiple serious negative health consequences. However, the epidemiological relationship between cigarette smoking and SARS-CoV-2 infection is controversial; and the interaction between cigarette smoking, airway expression of the ACE2 receptor and the susceptibility of airway cells to infection is unclear. We exposed differentiated air-liquid interface cultures derived from primary human airway stem cells to cigarette smoke extract (CSE) and infected them with SARS-CoV-2. We found that CSE increased expression of full-length ACE2 (flACE2) but did not alter the expression of a Type I-interferon sensitive truncated ACE2 that lacks the capacity to bind SARS-CoV-2 or a panel of interferon-sensitive genes. Importantly, exposure to CSE did not increase viral infectivity despite the increase in flACE2. Our data are consistent with epidemiological data suggesting current smokers are not at excess risk of SARS-CoV-2 infection. This does not detract from public health messaging emphasising the excess risk of severe COVID-19 associated with smoking-related cardiopulmonary disease.

scholarly journals Human parainfluenza virus type 1 regulates cholesterol biosynthesis and establishes quiescent infection in human airway cells

2021 ◽  
Vol 17 (9) ◽  
pp. e1009908
Author(s):  
Yuki Kurebayashi ◽  
Shringkhala Bajimaya ◽  
Masahiro Watanabe ◽  
Nicholas Lim ◽  
Michael Lutz ◽  
...  
Keyword(s):  
Virus Type ◽  
Cholesterol Biosynthesis ◽  
Parainfluenza Virus ◽  
Type I ◽  
Human Airway ◽  
Virion Release ◽  
Infected Cells ◽  
Human Parainfluenza Virus ◽  
Airway Cells

Human parainfluenza virus type 1 (hPIV1) and 3 (hPIV3) cause seasonal epidemics, but little is known about their interaction with human airway cells. In this study, we determined cytopathology, replication, and progeny virion release from human airway cells during long-term infection in vitro. Both viruses readily established persistent infection without causing significant cytopathic effects. However, assembly and release of hPIV1 rapidly declined in sharp contrast to hPIV3 due to impaired viral ribonucleocapsid (vRNP) trafficking and virus assembly. Transcriptomic analysis revealed that both viruses induced similar levels of type I and III IFNs. However, hPIV1 induced specific ISGs stronger than hPIV3, such as MX2, which bound to hPIV1 vRNPs in infected cells. In addition, hPIV1 but not hPIV3 suppressed genes involved in lipid biogenesis and hPIV1 infection resulted in ubiquitination and degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, a rate limiting enzyme in cholesterol biosynthesis. Consequently, formation of cholesterol-rich lipid rafts was impaired in hPIV1 infected cells. These results indicate that hPIV1 is capable of regulating cholesterol biogenesis, which likely together with ISGs contributes to establishment of a quiescent infection.

scholarly journals Cigarette Smoke Suppresses Type I Interferon-Mediated Antiviral Immunity in Lung Fibroblast and Epithelial Cells

2008 ◽  
Vol 28 (3) ◽  
pp. 167-179 ◽  
Author(s):  
Carla M.T. Bauer ◽  
Stephanie J. DeWitte-Orr ◽  
Kyle R. Hornby ◽  
Caleb C.J. Zavitz ◽  
Brian D. Lichty ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cigarette Smoke ◽  
Type I Interferon ◽  
Antiviral Immunity ◽  
Lung Fibroblast ◽  
Type I

scholarly journals Self-DNA release and STING-dependent sensing drives inflammation to cigarette smoke in mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mégane Nascimento ◽  
Aurélie Gombault ◽  
Norinne Lacerda-Queiroz ◽  
Corinne Panek ◽  
Florence Savigny ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Type I Interferon ◽  
Critical Role ◽  
Cigarette Smoke Exposure ◽  
Chronic Obstructive ◽  
Type I ◽  
Obstructive Pulmonary Disease ◽  
Interferon Pathway ◽  
Dna Release

Abstract Cigarette smoke exposure is a leading cause of chronic obstructive pulmonary disease (COPD), a major health issue characterized by airway inflammation with fibrosis and emphysema. Here we demonstrate that acute exposure to cigarette smoke causes respiratory barrier damage with the release of self-dsDNA in mice. This triggers the DNA sensor cGAS (cyclic GMP-AMP synthase) and stimulator of interferon genes (STING), driving type I interferon (IFN I) dependent lung inflammation, which are attenuated in cGAS, STING or type I interferon receptor (IFNAR) deficient mice. Therefore, we demonstrate a critical role of self-dsDNA release and of the cGAS-STING-type I interferon pathway upon cigarette smoke-induced damage, which may lead to therapeutic targets in COPD.

scholarly journals A Naturally Occurring Deletion in the Effector Domain of H5N1 Swine Influenza Virus Nonstructural Protein 1 Regulates Viral Fitness and Host Innate Immunity

2018 ◽  
Vol 92 (11) ◽  
Author(s):  
Junyong Wang ◽  
Yan Zeng ◽  
Shuai Xu ◽  
Jiayun Yang ◽  
Wanbing Wang ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Type I Interferon ◽  
Nonstructural Protein ◽  
Full Length ◽  
Type I ◽  
Effector Domain ◽  
Nonstructural Protein 1 ◽  
Naturally Occurring

ABSTRACT Nonstructural protein 1 (NS1) of influenza A virus regulates innate immune responses via various mechanisms. We previously showed that a naturally occurring deletion (the EALQR motif) in the NS1 effector domain of an H5N1 swine-origin avian influenza virus impairs the inhibition of type I interferon (IFN) in chicken fibroblasts and attenuates virulence in chickens. Here we found that the virus bearing this deletion in its NS1 effector domain showed diminished inhibition of IFN-related cytokine expression and attenuated virulence in mice. We further showed that deletion of the EALQR motif disrupted NS1 dimerization, impairing double-stranded RNA (dsRNA) sequestration and competitive binding with RIG-I. In addition, the EALQR-deleted NS1 protein could not bind to TRIM25, unlike full-length NS1, and was less able to block TRIM25 oligomerization and self-ubiquitination, further impairing the inhibition of TRIM25-mediated RIG-I ubiquitination compared to that with full-length NS1. Our data demonstrate that the EALQR deletion prevents NS1 from blocking RIG-I-mediated IFN induction via a novel mechanism to attenuate viral replication and virulence in mammalian cells and animals. IMPORTANCE H5 highly pathogenic avian influenza viruses have infected more than 800 individuals across 16 countries, with an overall case fatality rate of 53%. Among viral proteins, nonstructural protein 1 (NS1) of influenza virus is considered a key determinant for type I interferon (IFN) antagonism, pathogenicity, and host range. However, precisely how NS1 modulates virus-host interaction, facilitating virus survival, is not fully understood. Here we report that a naturally occurring deletion (of the EALQR motif) in the NS1 effector domain of an H5N1 swine-origin avian influenza virus disrupted NS1 dimerization, which diminished the blockade of IFN induction via the RIG-I signaling pathway, thereby impairing virus replication and virulence in the host. Our study demonstrates that the EALQR motif of NS1 regulates virus fitness to attain a virus-host compromise state in animals and identifies this critical motif as a potential target for the future development of small molecular drugs and attenuated vaccines.

370 Cigarette smoke products suppress anti-viral effects of Type I interferon via phosphorylation-dependent down-regulation of its receptor

Cytokine ◽  
2008 ◽  
Vol 43 (3) ◽  
pp. 331
Author(s):  
Wei-Chun HuangFu ◽  
Jianghuai Liu ◽  
Ronald N. Harty ◽  
Serge Y. Fuchs
Keyword(s):  
Cigarette Smoke ◽  
Type I Interferon ◽  
Type I ◽  
Down Regulation

scholarly journals Cigarette smoking products suppress anti-viral effects of Type I interferon via phosphorylation-dependent downregulation of its receptor

FEBS Letters ◽  
2008 ◽  
Vol 582 (21-22) ◽  
pp. 3206-3210 ◽  
Author(s):  
Wei-Chun HuangFu ◽  
Jianghuai Liu ◽  
Ronald N. Harty ◽  
Serge Y. Fuchs
Keyword(s):  
Cigarette Smoking ◽  
Type I Interferon ◽  
Type I
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