Influenza A matrix protein M2 downregulates CFTR: inhibition of chloride transport by a proton channel of the viral envelope

Vohwinkel, Christine U.; Vadász, István

doi:10.1152/ajplung.00091.2013

Cited by 6 publications

(4 citation statements)

References 31 publications

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“…Additionally, the question of whether ENaC regulates CFTR activity remains unclear (46). Furthermore, understanding the mechanism of the ENaC-CFTR cross talk in airway epithelia is complicated by the fact that CFTR activity and ENaC function are often affected by the same physiological [␤-agonists (7,179)] and environmental factors that include oxidative stress (19,20,175,203,218,248), hypoxia (36,244), inflammatory responses (28,30,169,202,241), and influenza infections (102,109,144,189,235).…”

Section: Chloride Transportmentioning

confidence: 99%

Ion channels of the lung and their role in disease pathogenesis

Bartoszewski

Matalon

Collawn

2017

American Journal of Physiology-Lung Cellular and Molecular Phys

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Maintenance of normal epithelial ion and water transport in the lungs includes providing a thin layer of surface liquid that coats the conducting airways. This airway surface liquid is critical for normal lung function in a number of ways but, perhaps most importantly, is required for normal mucociliary clearance and bacterial removal. Preservation of the appropriate level of hydration, pH, and viscosity for the airway surface liquid requires the proper regulation and function of a battery of different types of ion channels and transporters. Here we discuss how alterations in ion channel/transporter function often lead to lung pathologies.

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Section: Chloride Transportmentioning

confidence: 99%

Ion channels of the lung and their role in disease pathogenesis

Bartoszewski

Matalon

Collawn

2017

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…CFTR is a cyclic AMP-activated chloride (Cl − ) channel in lung epithelium that helps regulate the thickness and composition of lung epithelium-lining fluids. The pH increase in secretory pathways inhibits the CFTR activity by redirecting it to the ubiquitin-mediated proteasomal or lysosomal degradation system [ 128 , 129 ]. The M2 protein gradually increases intracellular levels of reactive oxygen species, possibly by altering the membrane potential across organelles such as mitochondria, that stimulate protein kinase C, increasing the endocytosis and proteasomal degradation of ENaC, culminating in reduction of its apical membrane levels and function ( Figure 3 ) [ 130 ].…”

Section: M2 Intracellular Trafficking and Its Impact On Host Cellsmentioning

confidence: 99%

“…The volume and composition of epithelial-lining fluids are maintained via a delicate functional balance between the secretion and absorption of fluids and electrolytes by Cl − and Na + channels, respectively; and both types of channels are present in apical membranes of lung epithelium [ 131 , 132 ]. Therefore, the M2-medated perturbation in the function of CFTR and ENaC is thought to be one of the factors leading to rhinorrhea and lung edema, causing exacerbation of respiratory pathology [ 128 , 129 , 130 ]. Another consequence of the M2-mediated perturbation in Golgi pH is activation of the NLRP3 inflammasome in dendritic cells and macrophages.…”

Section: M2 Intracellular Trafficking and Its Impact On Host Cellsmentioning

confidence: 99%

Influenza A Virus M2 Protein: Roles from Ingress to Egress

Manzoor

Igarashi

Takada

2017

IJMS

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Influenza A virus (IAV) matrix protein 2 (M2) is among the smallest bona fide, hence extensively studied, ion channel proteins. The M2 ion channel activity is not only essential for virus replication, but also involved in modulation of cellular homeostasis in a variety of ways. It is also the target for ion channel inhibitors, i.e., anti-influenza drugs. Thus far, several studies have been conducted to elucidate its biophysical characteristics, structure-function relationships of the ion channel, and the M2-host interactome. In this review, we discuss M2 protein synthesis and assembly into an ion channel, its roles in IAV replication, and the pathophysiological impact on the host cell.

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“…Given that influenza infections affect a large segment of the US population, the potential for flu epidemics, and the vulnerability of the aging population to flu's lethal consequences, understanding how flu affects CFTR and lung function is timely and important (reviewed in Ref. 75).…”

Section: Cftr and Influenzamentioning

confidence: 99%

CFTR and lung homeostasis

Collawn

Matalon

2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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CFTR is a cAMP-activated chloride and bicarbonate channel that is critical for lung homeostasis. Decreases in CFTR expression have dire consequences in cystic fibrosis (CF) and have been suggested to be a component of the lung pathology in chronic obstructive pulmonary disease. Decreases or loss of channel function often lead to mucus stasis, chronic bacterial infections, and the accompanying chronic inflammatory responses that promote progressive lung destruction, and, eventually in CF, lung failure. Here we discuss CFTR's functional role airway surface liquid hydration and pH, in regulation of other channels such as the epithelial sodium channel, and in regulating inflammatory responses in the lung.

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Influenza A matrix protein M2 downregulates CFTR: inhibition of chloride transport by a proton channel of the viral envelope

Cited by 6 publications

References 31 publications

Ion channels of the lung and their role in disease pathogenesis

Ion channels of the lung and their role in disease pathogenesis

Influenza A Virus M2 Protein: Roles from Ingress to Egress

CFTR and lung homeostasis

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