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Activation of STAT3-mediated ciliated cell survival protects against severe infection by respiratory syncytial virus
by
Mou, Hongmei
, Lukacs, Nicholas W.
, Olejnik, Judith
, Mühlberger, Elke
, Hume, Adam J.
, Wang, Wei
, Ai, Xingbin
, Amonkar, Gaurang M.
, Lerou, Paul H.
, Bai, Yan
, Zhao, Caiqi
, Fearns, Rachel
in
Adult
/ Adults
/ Age
/ Airway management
/ Animals
/ Apoptosis
/ Babies
/ Biopsy
/ Bronchopneumonia
/ Care and treatment
/ Cell activation
/ Cell cycle
/ Cell death
/ Cell Survival
/ Cilia - metabolism
/ Cilia - pathology
/ Cilia - virology
/ Cilia and ciliary motion
/ COVID-19 vaccines
/ Development and progression
/ Disease
/ Diseases
/ Epithelium
/ Female
/ Health aspects
/ Humans
/ Immune response
/ Infant
/ Infants
/ Infants (Newborn)
/ Infections
/ Infectious disease
/ Lungs
/ Male
/ Massachusetts
/ Medical research
/ Medicine, Experimental
/ Mice
/ Neonates
/ Newborn babies
/ Pediatric research
/ Respiratory Mucosa - metabolism
/ Respiratory Mucosa - pathology
/ Respiratory Mucosa - virology
/ Respiratory syncytial virus
/ Respiratory syncytial virus infection
/ Respiratory Syncytial Virus Infections - genetics
/ Respiratory Syncytial Virus Infections - metabolism
/ Respiratory Syncytial Virus Infections - pathology
/ Respiratory Syncytial Virus Infections - virology
/ Respiratory Syncytial Virus, Human - physiology
/ RNA sequencing
/ RNA viruses
/ Severe acute respiratory syndrome coronavirus 2
/ Stat3 protein
/ STAT3 Transcription Factor - genetics
/ STAT3 Transcription Factor - metabolism
/ United States
/ Viral infections
2024
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Activation of STAT3-mediated ciliated cell survival protects against severe infection by respiratory syncytial virus
by
Mou, Hongmei
, Lukacs, Nicholas W.
, Olejnik, Judith
, Mühlberger, Elke
, Hume, Adam J.
, Wang, Wei
, Ai, Xingbin
, Amonkar, Gaurang M.
, Lerou, Paul H.
, Bai, Yan
, Zhao, Caiqi
, Fearns, Rachel
in
Adult
/ Adults
/ Age
/ Airway management
/ Animals
/ Apoptosis
/ Babies
/ Biopsy
/ Bronchopneumonia
/ Care and treatment
/ Cell activation
/ Cell cycle
/ Cell death
/ Cell Survival
/ Cilia - metabolism
/ Cilia - pathology
/ Cilia - virology
/ Cilia and ciliary motion
/ COVID-19 vaccines
/ Development and progression
/ Disease
/ Diseases
/ Epithelium
/ Female
/ Health aspects
/ Humans
/ Immune response
/ Infant
/ Infants
/ Infants (Newborn)
/ Infections
/ Infectious disease
/ Lungs
/ Male
/ Massachusetts
/ Medical research
/ Medicine, Experimental
/ Mice
/ Neonates
/ Newborn babies
/ Pediatric research
/ Respiratory Mucosa - metabolism
/ Respiratory Mucosa - pathology
/ Respiratory Mucosa - virology
/ Respiratory syncytial virus
/ Respiratory syncytial virus infection
/ Respiratory Syncytial Virus Infections - genetics
/ Respiratory Syncytial Virus Infections - metabolism
/ Respiratory Syncytial Virus Infections - pathology
/ Respiratory Syncytial Virus Infections - virology
/ Respiratory Syncytial Virus, Human - physiology
/ RNA sequencing
/ RNA viruses
/ Severe acute respiratory syndrome coronavirus 2
/ Stat3 protein
/ STAT3 Transcription Factor - genetics
/ STAT3 Transcription Factor - metabolism
/ United States
/ Viral infections
2024
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Activation of STAT3-mediated ciliated cell survival protects against severe infection by respiratory syncytial virus
by
Mou, Hongmei
, Lukacs, Nicholas W.
, Olejnik, Judith
, Mühlberger, Elke
, Hume, Adam J.
, Wang, Wei
, Ai, Xingbin
, Amonkar, Gaurang M.
, Lerou, Paul H.
, Bai, Yan
, Zhao, Caiqi
, Fearns, Rachel
in
Adult
/ Adults
/ Age
/ Airway management
/ Animals
/ Apoptosis
/ Babies
/ Biopsy
/ Bronchopneumonia
/ Care and treatment
/ Cell activation
/ Cell cycle
/ Cell death
/ Cell Survival
/ Cilia - metabolism
/ Cilia - pathology
/ Cilia - virology
/ Cilia and ciliary motion
/ COVID-19 vaccines
/ Development and progression
/ Disease
/ Diseases
/ Epithelium
/ Female
/ Health aspects
/ Humans
/ Immune response
/ Infant
/ Infants
/ Infants (Newborn)
/ Infections
/ Infectious disease
/ Lungs
/ Male
/ Massachusetts
/ Medical research
/ Medicine, Experimental
/ Mice
/ Neonates
/ Newborn babies
/ Pediatric research
/ Respiratory Mucosa - metabolism
/ Respiratory Mucosa - pathology
/ Respiratory Mucosa - virology
/ Respiratory syncytial virus
/ Respiratory syncytial virus infection
/ Respiratory Syncytial Virus Infections - genetics
/ Respiratory Syncytial Virus Infections - metabolism
/ Respiratory Syncytial Virus Infections - pathology
/ Respiratory Syncytial Virus Infections - virology
/ Respiratory Syncytial Virus, Human - physiology
/ RNA sequencing
/ RNA viruses
/ Severe acute respiratory syndrome coronavirus 2
/ Stat3 protein
/ STAT3 Transcription Factor - genetics
/ STAT3 Transcription Factor - metabolism
/ United States
/ Viral infections
2024
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Activation of STAT3-mediated ciliated cell survival protects against severe infection by respiratory syncytial virus
Journal Article
Activation of STAT3-mediated ciliated cell survival protects against severe infection by respiratory syncytial virus
2024
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Overview
Respiratory syncytial virus (RSV) selectively targets ciliated cells in human bronchial epithelium and can cause bronchiolitis and pneumonia, mostly in infants. To identify molecular targets of intervention during RSV infection in infants, we investigated how age regulates RSV interaction with the bronchial epithelium barrier. Employing precision-cut lung slices and air-liquid interface cultures generated from infant and adult human donors, we found robust RSV virus spread and extensive apoptotic cell death only in infant bronchial epithelium. In contrast, adult bronchial epithelium showed no barrier damage and limited RSV infection. Single nuclear RNA-Seq revealed age-related insufficiency of an antiapoptotic STAT3 activation response to RSV infection in infant ciliated cells, which was exploited to facilitate virus spread via the extruded apoptotic ciliated cells carrying RSV. Activation of STAT3 and blockade of apoptosis rendered protection against severe RSV infection in infant bronchial epithelium. Lastly, apoptotic inhibitor treatment of a neonatal mouse model of RSV infection mitigated infection and inflammation in the lung. Taken together, our findings identify a STAT3-mediated antiapoptosis pathway as a target to battle severe RSV disease in infants.
Publisher
American Society for Clinical Investigation
Subject
/ Adults
/ Age
/ Animals
/ Babies
/ Biopsy
/ Disease
/ Diseases
/ Female
/ Humans
/ Infant
/ Infants
/ Lungs
/ Male
/ Mice
/ Neonates
/ Respiratory Mucosa - metabolism
/ Respiratory Mucosa - pathology
/ Respiratory Mucosa - virology
/ Respiratory syncytial virus infection
/ Respiratory Syncytial Virus Infections - genetics
/ Respiratory Syncytial Virus Infections - metabolism
/ Respiratory Syncytial Virus Infections - pathology
/ Respiratory Syncytial Virus Infections - virology
/ Respiratory Syncytial Virus, Human - physiology
/ Severe acute respiratory syndrome coronavirus 2
/ STAT3 Transcription Factor - genetics
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