Biology subjects

Mehedi, M.

Publications and source records attributed to Mehedi, M..

4 recordsLinked to original sources

bioRxiv2023

RSV infection does not induce EMT

Respiratory syncytial virus (RSV) infection does not cause severe disease in most of us despite suffering from multiple RSV infections in our lives. However, infants, young children, older adults, and immunocompromised patients are unfortunately vulnerable to RSV-associated severe diseases. A recent study suggested that RSV infection causes cell expansion, resulting in bronchial wall thickening in vitro. Whether the virus-induced changes in the lung airway resemble epithelial-mesenchymal transition (EMT) is still unknown. Here, we report that RSV does not induce EMT in three different in vitro lung models: the epithelial A549 cell line, primary normal human bronchial epithelial cells, and pseudostratified airway epithelium. We found that RSV increases the cell surface area and perimeter in the infected airway epithelium, which is distinct from the effects of a potent EMT inducer, TGF-{beta}1-driven cell elongation--indicative of cell motility. A genome-wide transcriptome analysis revealed that both RSV and TGF-{beta}1 have distinct modulation patterns of the transcriptome, which suggests that RSV-induced changes are distinct from EMT.

microbiology↗

bioRxiv2022

RSV-induced Expanded Ciliated Cells Contribute to Bronchial Wall Thickening

Viral infection, particularly respiratory syncytial virus (RSV), causes inflammation in the bronchiolar airways (bronchial wall thickening, also known as bronchiolitis), reducing airflow through the bronchioles. This bronchial wall thickening is a common pathophysiological feature in RSV infection, but it causes more fatalities in infants than in children and adults. However, the molecular mechanism of RSV-induced bronchial wall thickening remains unknown, particularly in healthy adults. RSV infection in the airway epithelium of healthy adult bronchial cells reveals RSV-infects primarily ciliated cells. RSV infection expands the cell cytoskeleton substantially without compromising epithelial membrane integrity and ciliary functions. The RSV-induced actin cytoskeleton expansion increases ununiformly epithelial height, and cytoskeletal (actin polymerization), immunological (INF-L1, TNF-, IP10/CXCL10), and viral (NS2) factors are probably responsible. Interestingly, RSV-infected cell cytoskeletons expansion resembles a noncanonical inflammatory phenotype, which contributes to bronchial wall thickening, and is termed cytoskeletal inflammation. Author SummaryRSV infects everyone. Although RSV-induced fatal pathophysiology (e.g., bronchiolitis) is more common in infants than adults, this bronchiolitis (or bronchial wall thickening) is common in the lower respiratory tract due to RSV infection in all ages. To determine the molecular mechanism of RSV-induced bronchial wall thickening, we infected in vitro adult airway epithelium with RSV. We found that RSV-infection induced a substantial actin-cytoskeleton expansion, consequently increased the height of the epithelium. We identified actin polymerization, secretion of proinflammatory cytokines and chemokines, and viral proteins contribute to the RSV-induced cytoskeletal expansion. Our results suggest that RSV-induces a novel noncanonical epithelial host response termed cytoskeletal inflammation, which may contribute to bronchial wall thickening.

microbiology↗

bioRxiv2022

Nuclear translocation of spike mRNA and protein is a novel pathogenic feature of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes severe pathophysiology in vulnerable older populations and appears to be highly pathogenic and more transmissible than SARS-CoV or MERS-CoV [1, 2]. The spike (S) protein appears to be a major pathogenic factor that contributes to the unique pathogenesis of SARS-CoV-2. Although the S protein is a surface transmembrane type 1 glycoprotein, it has been predicted to be translocated into the nucleus due to the novel nuclear localization signal (NLS) "PRRARSV", which is absent from the S protein of other coronaviruses. Indeed, S proteins translocate into the nucleus in SARS-CoV-2-infected cells. To our surprise, S mRNAs also translocate into the nucleus. S mRNA colocalizes with S protein, aiding the nuclear translocation of S mRNA. While nuclear translocation of nucleoprotein (N) has been shown in many coronaviruses, the nuclear translocation of both S mRNA and S protein reveals a novel pathogenic feature of SARS-CoV-2. Author summaryOne of the novel sequence insertions resides at the S1/S2 boundary of Spike (S) protein and constitutes a functional nuclear localization signal (NLS) motif "PRRARSV", which may supersede the importance of previously proposed polybasic furin cleavage site "RRAR". Indeed, S proteins NLS-driven nuclear translocation and its possible role in S mRNAs nuclear translocation reveal a novel pathogenic feature of SARS-CoV-2.

microbiology↗

bioRxiv2020

Goblet Cell Hyperplasia Increases SARS-CoV-2 Infection in COPD

SARS-CoV-2 has become a major problem across the globe, with approximately 50 million cases and more than 1 million deaths and currently no approved treatment or vaccine. Chronic obstructive pulmonary disease (COPD) is one of the underlying conditions in adults of any age that place them at risk for developing severe illness associated with COVID-19. We established an airway epithelium model to study SARS-CoV-2 infection in healthy and COPD lung cells. We found that both the entry receptor ACE2 and the co-factor transmembrane protease TMPRSS2 are expressed at higher levels on nonciliated goblet cell, a novel target for SARS-CoV-2 infection. We observed that SARS-CoV-2 infected goblet cells and induced syncytium formation and cell sloughing. We also found that SARS-CoV-2 replication was increased in the COPD airway epithelium likely due to COPD associated goblet cell hyperplasia. Our results reveal goblet cells play a critical role in SARS-CoV-2 infection in the lung.

microbiology↗