National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
5SC1GM139701
United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
5G12MD007603-30
United States
Simons Foundation
349247
United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM103310
United States
Department of Defense (DOD, United States)
W81XH19C0169
United States
Citation
Journal: Proc Natl Acad Sci U S A / Year: 2026 Title: Structure of Human adenovirus 7 virus-like particles, a platform for developing nanotherapeutics and studying capsid assembly. Authors: Kiyano Madoo / Ryan Mazboudi / Zubaida Marufee Islam / Jonathan Luo / Robert A Kuschner / Paul Gottlieb / John J Dennehy / Rinat R Abzalimov / Jose M Galarza / Reza Khayat / Abstract: Adenoviridae family members routinely infect humans, exhibit significant genetic diversity, and are associated with a variety of illnesses. Types 4 and 7 frequently circulate in the United States and ...Adenoviridae family members routinely infect humans, exhibit significant genetic diversity, and are associated with a variety of illnesses. Types 4 and 7 frequently circulate in the United States and are major causes of respiratory disease. Infections can result in hospitalization and, in severe cases, death. Although a live wild-type-virus vaccine targeting these two types exists, its use is restricted to military personnel due to concerns about viral-shedding and potential for genetic recombination. To overcome these limitations, we recently developed a virus-like particle (VLP) platform as an alternative vaccination strategy. These VLPs are stable, lack genomic material, and elicit a potent humoral immune response in mice, effectively neutralizing adenoviral infection. Here, we describe the cryo-EM structure of adenovirus 7 (AdV-7) VLPs. Structural insights are essential to ensure that neutralizing antigens displayed on the VLPs accurately mimic those of the virion, guide the design of particles with improved stability and efficacy, and enable engineering of VLPs with antigenic properties targeting multiple adenovirus types. The structure shows that hexon, penton, pIIIa, pVI, pVIII, and IX assemble comparable to AdV-5, hexon and penton neutralizing epitopes are appropriately displayed for antibody recognition, penton insertion into the hexon shell promotes cement protein pIIIa to increase its interaction with the peripentonal hexons, and presence of the core-genome is associated with increased interaction between cement protein pVIII and hexon. Finally, limited proteolysis and mass spectrometry demonstrate that VLP incorporated hexons digest more readily than virion incorporated hexons, indicating the greater dynamic nature of the VLP.
Shell ID: 1 / Name: Hexon / Diameter: 960.0 Å / T number (triangulation number): 25
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Experimental details
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Structure determination
Method
cryo EM
Processing
single particle reconstruction
Aggregation state
particle
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Sample preparation
Concentration
1 mg/mL
Buffer
pH: 7.4
Grid
Model: Quantifoil Active R2/1 / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY ARRAY / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Time: 30 sec. / Pretreatment - Atmosphere: AIR
Vitrification
Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV
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Electron microscopy
Microscope
TFS KRIOS
Image recording
Film or detector model: GATAN K3 BIOCONTINUUM (6k x 4k) / Digitization - Dimensions - Width: 5760 pixel / Digitization - Dimensions - Height: 4092 pixel / Number grids imaged: 1 / Number real images: 13608 / Average exposure time: 50.0 sec. / Average electron dose: 53.35 e/Å2 / Details: Not all images had particles
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
In the structure databanks used in Yorodumi, some data are registered as the other names, "COVID-19 virus" and "2019-nCoV". Here are the details of the virus and the list of structure data.
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