<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Role of Sphingolipid-interacting Proteins in \r\nInfluenza A Virus Infection"^^ . "Influenza A virus (IAV) is a significant cause of respiratory infections globally, with thousands \r\nof casualties annually. Its capacity for rapid antigenic variation in the surface glycoproteins, \r\nhemagglutinin (HA), and neuraminidase (NA) leads to the emergence of novel viral subtypes, \r\nthereby undermining vaccine efficacy and reinforcing its clinical relevance. During viral \r\nbudding in polarized cells, IAV utilizes lipid raFs - membrane microdomains enriched in \r\ncholesterol and sphingolipids (SLs) - at the apical side of the cell membrane, resulting in a viral\r\nenvelope enriched in these lipids. HA and NA, are characterized as raft-associated proteins, \r\nwhich are likely recruited to these domains during viral assembly. The NA1 protein, in \r\nparticular, might possess an SL-interac9ng motif, potentially aiding its localization to the \r\nbudding site. Additionally, the number of SLs increases during IAV infection, and defects in \r\nsphingomyelin (SM) synthesis affect the localization of viral glycoproteins to the plasma \r\nmembrane.\r\nDespite the established role of SLs in IAV infection, the precise molecular mechanisms by \r\nwhich specific SLs contribute to viral propagation, or how IAV modulates the SL metabolic \r\npathway, remain elusive. The involvement of SL-binding host proteins in viral replication has \r\nnot yet been thoroughly explored. To address this, a stable isotope labeling by amino acids in \r\ncell culture (SILAC) proteomics approach was employed, using bifunctional sphingosine to \r\nidentify SL-interacting proteins in infected and non-infected A549 cells (AG Brügger). Several \r\nSL-interacting protein hits were selected for further investigation in IAV infection based on \r\ntheir functional relevance and existing literature evidence of their roles in various viral \r\ninfections. Knockdown experiments assessed the impact of several candidate proteins on IAV \r\ninfection. Among these, ceramide synthase 2 (CerS2) was identified as a key protein with \r\npotential antiviral effect. CerS2 catalyzes the transfer of an acyl chain from acyl-CoA to a \r\nsphingoid base, with a high selectivity for very long-chain fatty acids. Infection of two \r\nA549ΔCerS2 clones with the PR8 strain of IAV displayed increased levels of viral nucleoprotein \r\n(NP) expression and plaque titers, with some clonal differences in HA titer. Notably, the reexpression of CerS2 in the A549ΔCerS2 cells led to a significant reduction in NP expression, HA \r\ntiters, and plaque formation, supporting the hypothesis of an antiviral function for CerS2 in \r\nIAV infection. However, the molecular mechanisms through which CerS2 influences IAV \r\ninfection remain to be elucidated in future studies. In summary, this study provides novel \r\ninsights into the role of sphingolipid-interacting proteins, particularly CerS2, in the replication \r\nand pathogenesis of IAV. These findings open new avenues for future research and may \r\ncontribute to the development of innovative therapeutic strategies aimed at combating IAV \r\ninfection"^^ . "2025" . . . . . . . "Jyothirmai"^^ . "Nethi"^^ . "Jyothirmai Nethi"^^ . . . . . . "Role of Sphingolipid-interacting Proteins in \r\nInfluenza A Virus Infection (PDF)"^^ . . . "Role of Sphingolipid-interacting Proteins in \r\nInfluenza A Virus Infection (Other)"^^ . . . . . . "Role of Sphingolipid-interacting Proteins in \r\nInfluenza A Virus Infection (Other)"^^ . . . . . . "Role of Sphingolipid-interacting Proteins in \r\nInfluenza A Virus Infection (Other)"^^ . . . . . . "Role of Sphingolipid-interacting Proteins in \r\nInfluenza A Virus Infection (Other)"^^ . . . . . . "Role of Sphingolipid-interacting Proteins in \r\nInfluenza A Virus Infection (Other)"^^ . . . . . "HTML Summary of #36058 \n\nRole of Sphingolipid-interacting Proteins in \nInfluenza A Virus Infection\n\n" . "text/html" . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .