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Viruses can get into cells in several ways. Figuring out how to stop them from entering in the first place is a key to developing better vaccines and stopping future pandemics. ....
Cell entry of most alphaherpesviruses is mediated by the binding of glycoprotein D (gD) to different cell surface receptors. Equine herpesvirus type 1 (EHV-1) and EHV-4 gDs interact with equine major histocompatibility complex I (MHC-I) to initiate entry into equine cells. We have characterized the gD-MHC-I interaction by solving the crystal structures of EHV-1 and EHV-4 gDs (gD1, gD4), performing protein-protein docking simulations, surface plasmon resonance (SPR) analysis, and biological assays. The structures of gD1 and gD4 revealed the existence of a common V-set immunoglobulin-like (IgV-like) core comparable to those of other gD homologs. Molecular modeling yielded plausible binding hypotheses and identified key residues (F213 and D261) that are important for virus binding. Altering the key residues resulted in impaired virus growth in cells, which highlights the important role of these residues in the gD-MHC-I interaction. Taken together, our results add to our understanding of t ....
2Laboratory for Pharmaceutical Biotechnology, University of Ghent, Ghent, Belgium 3ProGenTomics, Ghent, Belgium 4Laboratory of Proteinscience, Proteomics and Epigenetic Signaling, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium 5Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium Chikungunya virus (CHIKV) is an arbovirus with a global spread and significant public health impact. It is a positive stranded RNA alphavirus belonging to the Togaviridae family. However, many questions about the replication cycle of CHIKV remain unanswered. The entry process of CHIKV is not completely understood nor are the associated virus-receptor interactions fully identified. Here, we designed an affinity purification mass spectrometry coupled approach that allowed the identification of factors that facilitate entry of CHIKV in human cells. The identified entry factors were further validated using CRISP ....
February 15, 2021 Researchers have identified interactions between short viral proteins and receptors that facilitate the entry of the SARS-CoV-2 virus into a host. This evidence of molecular links, published in Science Signaling on February 12, may help scientists identify drugs that are highly effective at blocking the virus. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) as a receptor to attach to host cells. ACE2 is a single-pass type I membrane protein with a short cytosolic C-terminal region. While SARS-CoV-2 primarily binds to ACE2 in the lungs, previous studies have revealed that there is very little ACE2 gene expression in normal lungs, suggesting that the ACE2 receptor is insufficient on its own to establish severe lung disease. ....