The Effect of Fiber Truncations on the Stability of Adenovirus Type 5

Kupgan, Grit; Hentges, Danielle C.; Muschinske, Nathan J.; Picking, William D.; Picking, Wendy L.; Ramsey, Joshua D.

doi:10.1007/s12033-014-9777-6

Cited by 5 publications

(3 citation statements)

References 54 publications

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“…Indeed, species C Ad5 viruses were shown to release the fiber molecule upon cell binding, a step assumed to weaken the capsid and prime the disassembly process for protein VI release. In this context, fiberless Ad5 were shown to be less stable than native particles [ 358 ]. In contrast, non-matured, hyperstable Ts1 Ad2/5 do not release fiber or protein VI and are poor inducers of inflammation, since they are neither triggering TLR9 nor causing membrane damage [ 114 , 138 , 359 , 360 ].…”

Section: Modulating Adenovirus (Vaccine) Vector Efficacy the Capsid Leads The Waymentioning

confidence: 99%

Understanding Post Entry Sorting of Adenovirus Capsids; A Chance to Change Vaccine Vector Properties

Daussy

Pied

Wodrich

2021

Viruses

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Adenovirus vector-based genetic vaccines have emerged as a powerful strategy against the SARS-CoV-2 health crisis. This success is not unexpected because adenoviruses combine many desirable features of a genetic vaccine. They are highly immunogenic and have a low and well characterized pathogenic profile paired with technological approachability. Ongoing efforts to improve adenovirus-vaccine vectors include the use of rare serotypes and non-human adenoviruses. In this review, we focus on the viral capsid and how the choice of genotypes influences the uptake and subsequent subcellular sorting. We describe how understanding capsid properties, such as stability during the entry process, can change the fate of the entering particles and how this translates into differences in immunity outcomes. We discuss in detail how mutating the membrane lytic capsid protein VI affects species C viruses’ post-entry sorting and briefly discuss if such approaches could have a wider implication in vaccine and/or vector development.

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Section: Modulating Adenovirus (Vaccine) Vector Efficacy the Capsid Leads The Waymentioning

confidence: 99%

Understanding Post Entry Sorting of Adenovirus Capsids; A Chance to Change Vaccine Vector Properties

Daussy

Pied

Wodrich

2021

Viruses

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“…The virus core is enveloped by a capsid composed of major capsid proteins (hexon, penton, fiber) and minor capsid proteins (pIX, pIIIa, pVI, and pVIII). These capsid proteins are vital for stabilizing the structure of virus particles and play a crucial role in assembling and maintaining the integrity of the viral capsid [6][7][8][9]. HAdVs bind to cell surface receptors, initiating internalization via endocytosis [10].…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Demonstrates Innate Immunity Against Adenovirus-7 by Suppressing the NF-κB/JAK-STAT Pathway in a SIRT1-Dependent Manner

Wang,

Zhao

et al. 2023

Preprint

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The increasing incidence of severe adenovirus cases underscores the imperative for efficacious anti-adenovirus medications, given the current absence of targeted therapeutic options. This study explores the potential antiviral effects of the natural product Resveratrol (RSV) on various cell lines, marking the first-time discovery of such properties. The results suggest that RSV suppresses the upregulated pathways (NF-κB, JAK-STAT) triggered by viral infections, with its mechanism contingent upon the presence of the SIRT1 protein. Consequently, RSV mitigates the expression of inflammatory factors (IL-6, IL-8) as detected by ELISA. Subsequently, we elucidate the specific amino acid sites on both RSV and SIRT1 using macromolecular docking and protein docking methodologies. This revelation represents the pioneering elucidation of the mechanism and mode of action of resveratrol as an antiviral agent. These promising results establish the substantial potential of RSV as a therapeutic agent against adenovirus-7. The capacity to proficiently hinder adenovirus-7 replication and demonstrate potent antiviral properties in vitro experiments introduces novel avenues for crafting targeted therapies to combat adenovirus infections.

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“…Virion-associated fibers are commonly found in non-enveloped viruses infecting organisms ranging from bacteria to humans. These fibers assume a variety of functions, such as stabilizing the viral capsid ( 10 , 11 ), recognizing host receptors ( 12 ), facilitating virus attachment ( 13 ), and mediating host cell entry ( 14 , 15 ). For viruses infecting vertebrate hosts, viral fibers are often primary targets for neutralizing antibodies, as they are well exposed on capsid surfaces ( 16 , 17 ).…”

Section: Introductionmentioning

confidence: 99%

Orsay Virus CP-δ Adopts a Novel β-Bracelet Structural Fold and Incorporates into Virions as a Head Fiber

Guo

Fan

Zhou

et al. 2020

J Virol

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Fiber proteins are commonly found in eukaryotic and prokaryotic viruses where they play important roles in mediating viral attachment and host cell entry. They typically form trimeric structures and are incorporated into virions via non-covalent interactions. The small RNA virus Orsay, which specifically infects the laboratory model Caenorhabditis elegans, encodes a fibrous protein δ that can be expressed as a free protein and as a capsid protein-δ (CP-δ) fusion protein. Free δ has previously been demonstrated to facilitate viral exit following intracellular expression; however, the biological significance and prevalence of CP-δ remained relatively unknown. Here, we demonstrate that Orsay CP-δ is covalently incorporated into infectious particles, the first example of any attached viral fibers known to date. The crystal structure of δ (1-101) (i.e. a deletion mutant containing the first 101 amino acid (aa) residues of δ) reveals a pentameric, 145-Å long fiber with an N-terminal coiled coil followed by multiple β-bracelet repeats. Electron micrographs of infectious virions depict particle-associated CP-δ fibers with dimensions similar to free δ. δ proteins from two other nematode viruses Le Blanc and Santeuil, which both specifically infect Caenorhabditis briggsae, were also found to form fibrous molecules. Recombinant Le Blanc δ was able to block Orsay virus infection in worm culture and vice versa, suggesting these two viruses likely compete for the same cell receptor(s). Thus, we propose that while CP-δ likely mediates host cell attachment for all three nematode viruses, additional downstream factor(s) ultimately determine the host specificity and range of each virus. IMPORTANCE Viruses often have extended fibers to mediate host cell recognition and entry, serving as promising targets for antiviral drug development. Unlike other known viral fibers, the δ proteins from the three recently discovered nematode viruses are incorporated into infectious particles as protruding fibers covalently linked to the capsid. Crystal structures of δ revealed novel pentameric folding repeats, which we term β-bracelets, in the intermediate shaft region. Based on sequence analysis, the β-bracelet motif of δ is conserved in all three nematode viruses and could account for ∼60% of the total length of the fiber. Our study indicated that δ plays important roles in cell attachment for this group of nematode viruses. In addition, the tightly knitted β-bracelet fold, which presumably allows δ to survive harsh environments in the worm gut, could serve applicable to bioengineering applications given its potentially high stability.

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The Effect of Fiber Truncations on the Stability of Adenovirus Type 5

Cited by 5 publications

References 54 publications

Understanding Post Entry Sorting of Adenovirus Capsids; A Chance to Change Vaccine Vector Properties

Understanding Post Entry Sorting of Adenovirus Capsids; A Chance to Change Vaccine Vector Properties

Resveratrol Demonstrates Innate Immunity Against Adenovirus-7 by Suppressing the NF-κB/JAK-STAT Pathway in a SIRT1-Dependent Manner

Orsay Virus CP-δ Adopts a Novel β-Bracelet Structural Fold and Incorporates into Virions as a Head Fiber

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