scholarly journals IFITM dependency of SARS-CoV-2 variants of concern

2021 ◽  
Author(s):  
Rayhane Nchioua ◽  
Annika Schundner ◽  
Dorota Kmiec ◽  
Caterina Prelli Bozzo ◽  
Fabian Zech ◽  
...  
Keyword(s):  
The Netherlands ◽  
Infectious Virus ◽  
Transmembrane Proteins ◽  
Virus Production ◽  
Intermediate Phenotype ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Epithelial ◽  
N Terminus ◽  
Efficient Replication

We have recently shown that a SARS-CoV-2 strain isolated in the Netherlands in February 2020 (NL-02-2020) hijacks interferon-induced transmembrane proteins, especially IFITM2, as entry cofactors for efficient infection. Here, we examined whether SARS-CoV-2 'variants of concern' (VOCs), including the currently dominating delta variant, maintained the dependency on IFITMs for efficient replication. Depletion of IFITM2 reduced viral RNA production from 31- (B.1.1.7) to 755-fold (P.1). In comparison, silencing of IFITM1 had little effect, while knock-down of IFITM3 resulted in an intermediate phenotype. Strikingly, silencing of IFITM2 generally reduced infectious virus production in Calu-3 cells to near background levels. An antibody directed against the N-terminus of IFITM2 inhibited SARS-CoV-2 VOC replication in iPSC-derived alveolar epithelial type II cells. In conclusion, endogenously expressed IFITM proteins (especially IFITM2) are important cofactors for replication of genuine SARS-CoV-2 VOCs, including the Delta variant.

scholarly journals SARS-CoV-2 variants of concern are dependent on IFITM2 for efficient replication in human lung cells

2021 ◽  
Author(s):  
Rayhane Nchioua ◽  
Annika Schundner ◽  
Dorota Kmiec ◽  
Caterina Prelli Bozzo ◽  
Fabian Zech ◽  
...  
Keyword(s):  
Cancer Cell Line ◽  
Virus Production ◽  
Lung Cancer Cell Line ◽  
Intermediate Phenotype ◽  
Target Cells ◽  
Lung Cancer Cell ◽  
Alveolar Epithelial ◽  
Human Lung Cells ◽  
Efficient Replication ◽  
Viral Target

It has recently been shown that an early SARS-CoV-2 isolate (NL-02-2020) hijacks interferon-induced transmembrane proteins (IFITMs) for efficient replication in human cells. To date, several "Variants of Concern" (VOCs) showing increased infectivity and resistance to neutralization have emerged and globally replaced the early viral strains. Here, we determined whether the four SARS-CoV-2 VOCs (Alpha, Beta, Gamma and Delta) maintained the dependency on IFITM proteins for efficient replication. We found that depletion of IFITM2 strongly reduces viral RNA production by all four VOCs in the human epithelial lung cancer cell line Calu-3. Silencing of IFITM1 had little effect, while knock-down of IFITM3 resulted in an intermediate phenotype. Strikingly, depletion of IFITM2 generally reduced infectious virus production by more than four orders of magnitude. In addition, an antibody directed against the N-terminus of IFITM2 inhibited SARS-CoV-2 VOC replication in iPSC-derived alveolar epithelial type II cells thought to represent major viral target cells in the lung. In conclusion, endogenously expressed IFITM proteins (especially IFITM2) are critical cofactors for efficient replication of genuine SARS-CoV-2 VOCs, including the currently dominating Delta variant.

Disparate cytokine regulation of ICAM-1 in rat alveolar epithelial cells and pulmonary endothelial cells in vitro

1995 ◽  
Vol 269 (1) ◽  
pp. L127-L135 ◽  
Author(s):  
W. W. Barton ◽  
S. Wilcoxen ◽  
P. J. Christensen ◽  
R. Paine
Keyword(s):  
Endothelial Cells ◽  
Epithelial Cells ◽  
Inflammatory Cytokines ◽  
Alveolar Epithelial Cells ◽  
Normal Lung ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Epithelial

Intercellular adhesion molecule-1 (ICAM-1) is expressed at high levels on type I alveolar epithelial cells in the normal lung and is induced in vitro as type II cells spread in primary culture. In contrast, in most nonhematopoetic cells ICAM-1 expression is induced in response to inflammatory cytokines. We have formed the hypothesis that the signals that control ICAM-1 expression in alveolar epithelial cells are fundamentally different from those controlling expression in most other cells. To test this hypothesis, we have investigated the influence of inflammatory cytokines on ICAM-1 expression in isolated type II cells that have spread in culture and compared this response to that of rat pulmonary artery endothelial cells (RPAEC). ICAM-1 protein, determined both by a cell-based enzyme-linked immunosorbent assay and by Western blot analysis, and mRNA were minimally expressed in unstimulated RPAEC but were significantly induced in a time- and dose-dependent manner by treatment with tumor necrosis factor-alpha, interleukin-1 beta, or interferon-gamma. In contrast, these cytokines did not influence the constitutive high level ICAM-1 protein expression in alveolar epithelial cells and only minimally affected steady-state mRNA levels. ICAM-1 mRNA half-life, measured in the presence of actinomycin D, was relatively long at 7 h in alveolar epithelial cells and 4 h in RPAEC. The striking lack of response of ICAM-1 expression by alveolar epithelial cells to inflammatory cytokines is in contrast to virtually all other epithelial cells studied to date and supports the hypothesis that ICAM-1 expression by these cells is a function of cellular differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals A Site-Specific Genetic Modification for Induction of Pluripotency and Subsequent Isolation of Derived Lung Alveolar Epithelial Type II Cells

Stem Cells ◽  
2014 ◽  
Vol 32 (2) ◽  
pp. 402-413 ◽  
Author(s):  
Qing Yan ◽  
Yuan Quan ◽  
Huanhuan Sun ◽  
Xinmiao Peng ◽  
Zhengyun Zou ◽  
...  
Keyword(s):  
Genetic Modification ◽  
Type Ii Cells ◽  
Type Ii ◽  
Site Specific ◽  
Alveolar Epithelial ◽  
A Site

Secretion of cytokines by rat alveolar epithelial cells: possible regulatory role for SP-A

1994 ◽  
Vol 266 (2) ◽  
pp. L148-L155 ◽  
Author(s):  
H. Blau ◽  
S. Riklis ◽  
V. Kravtsov ◽  
M. Kalina
Keyword(s):  
Epithelial Cells ◽  
Alveolar Epithelial Cells ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Type Ii Cells ◽  
Long Term Culture ◽  
Alveolar Epithelial ◽  
Gm Csf

Cultured alveolar type II cells and pulmonary epithelial (PE) cells in long-term culture were found to secrete colony-stimulating factors (CSF) into the medium in similar fashion to alveolar macrophages. CSF activity was determined by using the in vitro assay for myeloid progenitor cells [colony-forming units in culture (CFU-C)]. Both lipopolisaccharide (LPS) and interleukin-1 alpha (IL-1 alpha) were found to upregulate the secretion 6.5- to 8-fold from alveolar type II cells and macrophages. However, no stimulatory effect of these factors was observed in PE cells that release CSF into the medium constitutively, possibly due to the conditions of long-term culture. The CSF activity was partially neutralized (70% inhibition) by antibodies against murine granulocyte/macrophage (GM)-CSF and IL-3, thus indicating the presence of both GM-CSF and IL-3-like factors in the CSF. However, the presence of other cytokines in the CSF is highly probable. Surfactant-associated protein A (SP-A), which is known to play a central role in surfactant homeostasis and function, was also found to upregulate secretion of CSF (at concentrations of 0.1-5 micrograms/ml) from alveolar type II cells and macrophages. Control cells such as rat peritoneal macrophages, alveolar fibroblasts, and 3T3/NIH cell line could not be elicited by SP-A to release CSF. The results are discussed in relation to the possible participation of the alveolar epithelial cells in various intercellular signaling networks. Our studies suggest that alveolar type II cells and SP-A may play an important regulatory role in the modulation of immune and inflammatory effector cells within the alveolar space.

scholarly journals The plate body: 3D ultrastructure of a facultative organelle of alveolar epithelial type II cells involved in SP-A trafficking

2020 ◽  
Author(s):  
Christian Mühlfeld ◽  
Christoph Wrede ◽  
Viktor Molnár ◽  
Alexandra Rajces ◽  
Christina Brandenberger
Keyword(s):  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Epithelial

Cyclic deformation-induced injury and differentiation of rat alveolar epithelial type II cells

2012 ◽  
Vol 180 (2-3) ◽  
pp. 237-246 ◽  
Author(s):  
Huan Ye ◽  
Qingyuan Zhan ◽  
Yanhong Ren ◽  
Xiaoyang Liu ◽  
Chun Yang ◽  
...  
Keyword(s):  
Cyclic Deformation ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Epithelial
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