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Identification of the epithelial receptor for measles virus

ABSTRACT: Measles (MV) is an aerosol-transmitted virus that affects more than 10 million children each year and accounts for approximately 120,000 deaths. While it was long believed to replicate in the respiratory epithelium before disseminating, it was recently shown to initially infect macrophages and dendritic cells of the airways using the signaling lymphocytic activation molecule (SLAM, CD150) as receptor. These cells then cross the respiratory epithelium and ferry the infection to lymphatic organs where MV replicates vigorously. How and where the virus crosses back into the airways has remained unknown. However, certain carcinoma cell lines have been described to be either permissive for wt MV infection, or not (Leonard VHJ et al. 2008). Therefor, we decided to compare the expression pattern of permissive and non-permissive cell lines by micro array analysis. Based on functional analyses of surface proteins preferentially expressed on virus-permissive epithelial cell lines, we identified nectin-4 (poliovirus-receptor-like-4) as a candidate receptor.

ORGANISM(S): Homo sapiens

PROVIDER: GSE32155 | GEO | 2011/11/02

SECONDARY ACCESSION(S): PRJNA147629

REPOSITORIES: GEO

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Identification of the epithelial receptor for measles virus

Project description:Measles (MV) is an aerosol-transmitted virus that affects more than 10 million children each year and accounts for approximately 120,000 deaths. While it was long believed to replicate in the respiratory epithelium before disseminating, it was recently shown to initially infect macrophages and dendritic cells of the airways using the signaling lymphocytic activation molecule (SLAM, CD150) as receptor. These cells then cross the respiratory epithelium and ferry the infection to lymphatic organs where MV replicates vigorously. How and where the virus crosses back into the airways has remained unknown. However, certain carcinoma cell lines have been described to be either permissive for wt MV infection, or not (Leonard VHJ et al. 2008). Therefor, we decided to compare the expression pattern of permissive and non-permissive cell lines by micro array analysis. Based on functional analyses of surface proteins preferentially expressed on virus-permissive epithelial cell lines, we identified nectin-4 (poliovirus-receptor-like-4) as a candidate receptor. The dataset comprises 21 samples divided into seven sample groups each representing 3 biological replicates of one out of 7 cell lines.

2011-11-02 | E-GEOD-32155 | biostudies-arrayexpress

The Isolation and In vitro Differentiation of Primary Fetal Baboon Tracheal Epithelial Cells for the Study of SARS-CoV-2 Host-Virus Interactions

Project description:The mucociliary airway epithelium lines the human airways and is the primary site of host-environmental interactions in the lung. Following virus infection, airway epithelial cells initiate an innate immune response to suppress virus replication. Therefore, defining the virus-host interactions of the mucociliary airway epithelium is critical for understanding the mechanisms that regulate virus infection, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Non-human primates (NHP) are closely related to humans; and provide a model to study human disease. However, ethical considerations and high costs can restrict the use of in vivo NHP models. Therefore, there is a need to develop in vitro NHP models of human respiratory virus infection that would allow for rapidly characterizing virus tropism and suitability of specific NHP species to model human infection. Using the olive baboon (Papio anubis), we have developed methodologies for the isolation, in vitro expansion, cryopreservation, and mucociliary differentiation of primary fetal baboon tracheal epithelial cells (FBTECs). Furthermore, we demonstrate that in vitro differentiated FBTECs are permissive to SARS-CoV-2 infection and produce a potent host innate-immune response. In summary, we have developed an in vitro NHP model that provides a platform for the study of SARS-CoV-2 infection and other human respiratory viruses.

2023-03-14 | GSE226820 | GEO

TLR-2-mediated activation of innate responses in the upper airways confers rapid anti-viral protection of the lungs

Project description:The impact of respiratory virus infections on global health is felt not just during a pandemic but for many, endemic seasonal infections pose an equal and ongoing risk of severe disease. Moreover, vaccines and antiviral drugs are not always effective or available for many respiratory viruses. We investigated how induction of effective and appropriate antigen independent innate immunity in the upper airways can prevent spread of respiratory virus infection to the vulnerable lower airways. Activation of Toll-like receptor-2 (TLR2), when restricted to the nasal turbinates results in prompt induction of innate immune-driven anti-viral responses through action of cytokines, chemokines and cellular activity in the upper but not the lower airways. We define how nasal epithelial cells and recruitment of macrophages work in concert and play pivotal roles to limit progression of influenza virus to the lungs and sustain protection for up to seven days. These results reveal underlying mechanisms of how control of viral infection in the upper airways can occur and also support the implementation of strategies that can activate TLR2 in nasal passages to provide rapid protection, especially for at-risk populations, against severe respiratory infection when vaccines and antiviral drugs are not always effective or available.

2021-06-08 | PXD023041 | Pride

PVRL Is A Receptor For Measles Virus

2011-07-29 | GSE26636 | GEO

PVRL Is A Receptor For Measles Virus

Project description:Measles virus infects serum activated airway epithelial cells and many adenocarcinoma cell lines. A microarray analysis was performed on virus permissive versus non-permissive cells. Membrane protein genes that were upregulated in permissive cells were tested as receptor/entry factors. Membrane protein genes that were upregulated in smooth airway epithelial cells (SAEC) following growth in 10% fetal calf serum that made the cell line permissive to measles virus were identified. Membrane protein genes that were upregulated in adenocarcinoma cells that were permissive to wild type measles virus infection were identified. [SAEC]: Airway cells (SAEC) grown in serum free media (SAGM) were purchaced from Lonza. Half the cells were cultured in SAGM, the other half were transferred into Dulbecco's 10% fetal calf serum for 24 hrs. RNA was harvested from the cells by the Qiagen RNAeasy [Adenocarcinoma cells]: MCF7, MDA-MB-468, T47D, NCI-H358, NCI-H125, MGH24 cells were permissive and A549 and MDA-MB-231 cells were non-permissive.

2011-07-28 | E-GEOD-26636 | biostudies-arrayexpress

APOBEC3G-regulated host factors interfere with measles virus replication: role of REDD1 and KDELR2

Project description:Classically, the cytidine deaminase APOBEC3G (A3G) exerts antiviral activity against transposable elements, retroviruses, and hepatitis B virus. However, we found earlier, that it also inhibits measles (MV), mumps (MuV) and respiratory syncytial virus (RSV), but the mechanism of inhibition remained unclear. Because A3G is present in RNA processing (P) bodies, where it is involved in the regulation of mRNA decay, we supposed that it may influence the expression of host cell factors, some of which may affect viral replication. Using a microarray we therefore assessed in Vero cells whether A3G expression influences the cellular gene expression. We found alterations indicating 844 up-regulated and 598 down-regulated transcripts (adjusted P values < 0.05). Of these trancripts 19 were up-regulated and 23 down-regulated by a factor of > 2. One of the down-regulated factors, MOSC2, appeared to support MV replication, since shRNA-mediated MOSC2 knock down reduced MV replication. In addition, two up-regulated factors, REDD1 and KDELR2, impaired MV replication when over-expressed in VeroREDD1 is a cellular inhibitor of mTORC1, a regulator of cellular homeostasis controlling cell growth and protein synthesis. Rapamycin also reduced MV replication confirming our findings with REDD1. The KDELR2 retains chaperons in the ER, which are required for proper folding and transport of MV glycoproteins to the cell surface, and thereby reduces MV glycoprotein expression at the cell surface, syncytium formation, and the formation of infectious virus.

2018-06-18 | GSE85102 | GEO

Host responses that correlate with respiratory droplet transmission of swine-origin influenza viruses in ferrets.

Project description:The determinants of influenza transmission remain poorly understood. Swine influenza viruses preferentially attach to receptors found in the upper airways; however, most swine influenza viruses fail to transmit efficiently from swine to humans, and from human-to-human. The pandemic 2009 H1N1 (H1N1pdm) virus was a rare exception of a swine virus that acquired efficient transmissibility from human-to-human, and is reflected in efficient respiratory droplet transmission in ferrets. We hypothesize that virus-induced host responses in the upper airways correlate with airborne transmission in ferrets. To address this question, we used the H1N1pdm virus and swine influenza A/swine/Hong Kong/201/2010 (HK201) virus that has comparable titre in the ferret nasopharynx, but it exhibits differential transmissibility in ferrets via respiratory droplet route. We performed a transcriptomic analysis of tissues from the upper and lower respiratory tract from ferrets infected with either H1N1pdm or HK201 viruses using ferret-specific Agilent oligonucleotide arrays. We found differences in the kinetics of the innate immune response elicited by these two viruses that varied across tissues.

2017-03-31 | GSE79282 | GEO

Transcription profiling of human bronchial epithelial cells from normal and asthmatic subjects exposed to either ozone or rhinovirus

Project description:The exacerbation of disease in asthmatics has been linked to both exposure to environmental agents as well as to the presence of virus in airways, particularly rhinovirus. The hypothesis tested in these experiments is that differences in gene expression profiles in epithelial cells derived from asthmatic and normal airways can be linked to enhanced responsiveness of the epithelium in its pro-inflammatory, immulogic or other activities that may lead to the exacerbation of disease.

2007-12-12 | E-GEOD-470 | biostudies-arrayexpress

Bovine Respiratory Disease Complex

Project description:Bovine respiratory epithelial cells have different susceptibility to bovine respiratory syncytial virus infection. The cells derived from the lower respiratory tract were significantly more susceptible to the virus than those derived from the upper respiratory tract. Pre-infection with virus of lower respiratory tract with increased adherence of P. multocida; this was not the case for upper tract. However, the molecular mechanisms of enhanced bacterial adherence are not completely understood. To investigate whether virus infection regulates the cellular adherence receptor on bovine trachea-, bronchus- and lung-epithelial cells, we performed proteomic analyses.

2020-07-28 | PXD019509 | JPOST Repository

The impact of influenza pulmonary infection and inflammation on vagal bronchopulmonary sensory neurons

Project description:Influenza A virus (IAV) is rapidly detected in the airways by the immune system, with resident parenchymal cells and leukocytes orchestrating viral sensing and the induction of antiviral inflammatory responses. The airways are innervated by heterogenous populations of vagal sensory neurons which also play an important role in pulmonary defense. How these neurons respond to IAV respiratory infection remains unclear. Here, we use a murine model to provide the first evidence that vagal sensory neurons undergo significant transcriptional changes following a respiratory IAV infection. RNA sequencing on vagal sensory ganglia showed that IAV infection induced the expression of many genes associated with an antiviral and pro-inflammatory response

2021-06-20 | GSE161878 | GEO

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