Cryo-electron tomography (cryo-ET) has emerged as a powerful tool in structural biology to study viruses and is undergoing a resolution revolution. Enveloped viruses comprise several RNA and DNA pleomorphic viruses that are pathogens of clinical importance to humans and animals. Considerable efforts in cryogenic correlative light and electron microscopy (cryo-CLEM), cryogenic focused ion beam milling (cryo-FIB), and integrative structural techniques are helping to identify virus structures within cells leading to a rise of in situ discoveries shedding light on how viruses interact with their hosts during different stages of infection. This chapter reviews recent advances in the application of cryo-ET in imaging enveloped viruses and the structural and mechanistic insights revealed studying the viral infection cycle within their eukaryotic cellular hosts, with particular attention to viral entry, replication, assembly, and egress during infection.
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http://dx.doi.org/10.1007/978-3-031-40086-5_1 | DOI Listing |
PLoS Pathog
January 2025
Microbial Sciences Institute, Yale University, West Haven, Connecticut, United States of America.
Spirochetes are a widely existing group of bacteria with a distinct morphology. Some spirochetes are important human pathogens that utilize periplasmic flagella to achieve motility and host infection. The motors that drive the rotation of periplasmic flagella have a unique spirochete-specific feature, termed the collar, crucial for the flat-wave morphology and motility of the Lyme disease spirochete Borrelia burgdorferi.
View Article and Find Full Text PDFNat Commun
January 2025
Key Laboratory for Protein Sciences of Ministry of Education, School of Life Sciences, Tsinghua University, Beijing, China.
Advancements in cryo-electron tomography (cryoET) allow the structure of macromolecules to be determined in situ, which is crucial for studying membrane protein structures and their interactions in the cellular environment. However, membranes are often highly curved and have a strong contrast in cryoET tomograms, which masks the signals from membrane proteins. These factors pose difficulties in observing and revealing the structures of membrane proteins in situ.
View Article and Find Full Text PDFNat Commun
January 2025
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
The continuing emergence of immune evasive SARS-CoV-2 variants and the previous SARS-CoV-1 outbreak collectively underscore the need for broadly protective sarbecovirus vaccines. Targeting the conserved S2 subunit of SARS-CoV-2 is a particularly promising approach to elicit broad protection. Here, we describe a nanoparticle vaccine displaying multiple copies of the SARS-CoV-1 S2 subunit.
View Article and Find Full Text PDFHIV-1 assembly is initiated by the binding of Gag polyproteins to the inner leaflet of the plasma membrane, mediated by the myristylated matrix (MA) domain of Gag. Subsequent to membrane binding, Gag oligomerizes and buds as an immature, non-infectious virus particle, which, upon cleavage of the Gag precursor by the viral protease, transforms into a mature, infectious virion. During maturation, the MA lattice underlying the viral membrane undergoes a structural rearrangement and the newly released capsid (CA) protein forms a mature capsid that encloses the viral genome.
View Article and Find Full Text PDFIt is now possible to generate large volumes of high-quality images of biomolecules at near-atomic resolution and in near-native states using cryogenic electron microscopy/electron tomography (Cryo-EM/ET). However, the precise annotation of structures like filaments and membranes remains a major barrier towards applying these methods in high-throughput. To address this, we present TARDIS ( ransformer-b sed apid imensionless nstance egmentation), a machine-learning framework for fast and accurate annotation of micrographs and tomograms.
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