by Keyword: entry
Monteil, VM, Wright, SC, Dyczynski, M, Kellner, MJ, Appelberg, S, Platzer, SW, Ibrahim, A, Kwon, H, Pittarokoilis, I, Mirandola, M, Michlits, G, Devignot, S, Elder, E, Abdurahman, S, Bereczky, S, Bagci, B, Youhanna, S, Aastrup, T, Lauschke, VM, Salata, C, Elaldi, N, Weber, F, Monserrat, N, Hawman, DW, Feldmann, H, Horn, M, Penninger, JM, Mirazimi, A, (2024). Crimean-Congo haemorrhagic fever virus uses LDLR to bind and enter host cells Nature Microbiology 9, 1499-1512 
Climate change and population densities accelerated transmission of highly pathogenic viruses to humans, including the Crimean-Congo haemorrhagic fever virus (CCHFV). Here we report that the Low Density Lipoprotein Receptor (LDLR) is a critical receptor for CCHFV cell entry, playing a vital role in CCHFV infection in cell culture and blood vessel organoids. The interaction between CCHFV and LDLR is highly specific, with other members of the LDLR protein family failing to bind to or neutralize the virus. Biosensor experiments demonstrate that LDLR specifically binds the surface glycoproteins of CCHFV. Importantly, mice lacking LDLR exhibit a delay in CCHFV-induced disease. Furthermore, we identified the presence of Apolipoprotein E (ApoE) on CCHFV particles. Our findings highlight the essential role of LDLR in CCHFV infection, irrespective of ApoE presence, when the virus is produced in tick cells. This discovery holds profound implications for the development of future therapies against CCHFV. Laboratory and clinical strains of Crimean-Congo haemorrhagic fever virus use LDLR to bind and enter host cells in blood vessel organoids and mice. Infection can also occur through ApoE, possibly present on virus particles.
JTD Keywords: Cholesterol, Clathrin, Entry requires, Genetics, Localization, Protei, Receptor
Acosta-Gutierrez, S, Buckley, J, Battaglia, G, (2023). The Role of Host Cell Glycans on Virus Infectivity: The SARS-CoV-2 Case Advanced Science 10, 2201853
Glycans are ubiquitously expressed sugars, coating the cell and protein surfaces. They are found on many proteins as either short and branched chains or long chains sticking out from special membrane proteins, known as proteoglycans. This sugar cushion, the glycocalyx, modulates specific interactions and protects the cell. Here it is shown that both the expression of proteoglycans and the glycans expressed on the surface of both the host and virus proteins have a critical role in modulating viral attachment to the cell. A mathematical model using SARS-Cov-2 as an archetypical virus to study the glycan role during infection is proposed. It is shown that this occurs via a tug-of-war of forces. On one side, the multivalent molecular recognition that viral proteins have toward specific host glycans and receptors. On the other side, the glycan steric repulsion that a virus must overcome to approach such specific receptors. By balancing both interactions, viral tropism can be predicted. In other words, the authors can map out the cells susceptible to virus infection in terms of receptors and proteoglycans compositions.© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.
JTD Keywords: binding, entry, glycocalyx, mechanisms, multiplexing, multivalency, nanoparticles, recognition, super-selectivity, viral infectivity, Functional receptor, Glycans, Glycocalyx, Multiplexing, Multivalency, Nanoparticles, Super-selectivity, Viral infectivity
