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Tate, John; Liljas, Lars; Scotti, Paul D.; Christian, Peter D.; Lin, Tianwei; Johnson, John E.

doi:10.1038/11543

Cited by 112 publications

(80 citation statements)

References 45 publications

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“…The template structures used by I-TASSER for VP0 were foot-and-mouth disease virus (PDB identifiers [IDs] 1QQP, 1FMD, and 1BBT) (32-34), poliovirus 1 (PDB ID 1POV) (35), bovine enterovirus (PDB ID 1BEV) (36), and Seneca Valley virus 001 (PDB ID 3CJI) (37). For VP1, they were Triatoma virus (PDB ID 3NAP) (38), human rhinovirus 14 (PDB ID 1D3I) (39), cricket paralysis virus (PDB ID 1B35) (40), rabbit hemorrhagic disease virus (PDB ID 4EJR) (41), echovirus 7 (PDB ID 1M11) (42), and bovine enterovirus (PDB ID 1BEV) (36). For VP3, they were human enterovirus 71 (PDB ID 3VBF) (43), Seneca Valley virus 001 (PDB ID 3CJI) (37), human rhinovirus 16 (PDB ID 1AYM) (44), and poliovirus Mahoney strain (PDB ID 1HXS) (45).…”

Section: Methodsmentioning

confidence: 99%

Structural Basis of Human Parechovirus Neutralization by Human Monoclonal Antibodies

Shakeel

Westerhuis

Ora

et al. 2015

J Virol

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Since it was first recognized in 2004 that human parechoviruses (HPeV) are a significant cause of central nervous system and neonatal sepsis, their clinical importance, primarily in children, has started to emerge. Intravenous immunoglobulin treatment is the only treatment available in such life-threatening cases and has given moderate success. Direct inhibition of parechovirus infection using monoclonal antibodies is a potential treatment. We have developed two neutralizing monoclonal antibodies against HPeV1 and HPeV2, namely, AM18 and AM28, which also cross-neutralize other viruses. Here, we present the mapping of their epitopes using peptide scanning, surface plasmon resonance, fluorescence-based thermal shift assays, electron cryomicroscopy, and image reconstruction. We determined by peptide scanning and surface plasmon resonance that AM18 recognizes a linear epitope motif including the arginine-glycine-aspartic acid on the C terminus of capsid protein VP1. This epitope is normally used by the virus to attach to host cell surface integrins during entry and is found in 3 other viruses that AM18 neutralizes. Therefore, AM18 is likely to cause virus neutralization by aggregation and by blocking integrin binding to the capsid. Further, we show by electron cryomicroscopy, three-dimensional reconstruction, and pseudoatomic model fitting that ordered RNA interacts with HPeV1 VP1 and VP3. AM28 recognizes quaternary epitopes on the capsid composed of VP0 and VP3 loops from neighboring pentamers, thereby increasing the RNA accessibility temperature for the virus-AM28 complex compared to the virus alone. Thus, inhibition of RNA uncoating probably contributes to neutralization by AM28. IMPORTANCEHuman parechoviruses can cause mild infections to severe diseases in young children, such as neonatal sepsis, encephalitis, and cardiomyopathy. Intravenous immunoglobulin treatment is the only treatment available in such life-threatening cases. In order to develop more targeted treatment, we have searched for human monoclonal antibodies that would neutralize human parechoviruses 1 and 2, associated with mild infections such as gastroenteritis and severe infections of the central nervous system, and thus allow safe treatment. In the current study, we show how two such promising antibodies interact with the virus, modeling the atomic interactions between the virus and the antibody to propose how neutralization occurs. Both antibodies can cause aggregation; in addition, one antibody interferes with the virus recognizing its target cell, while the other, recognizing only the whole virus, inhibits the genome uncoating and replication in the cell. Human parechoviruses (HPeV) are single-stranded, positivesense RNA viruses in the Parechovirus genus within the Picornaviridae family (1). HPeV infections mainly cause mild gastrointestinal symptoms, although HPeV are also associated with more severe central nervous system symptoms, such as meningitis and neonatal sepsis (2-5). The HPeV genome is about 7,300 bases in length, enclose...

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Section: Methodsmentioning

confidence: 99%

Structural Basis of Human Parechovirus Neutralization by Human Monoclonal Antibodies

Shakeel

Westerhuis

Ora

et al. 2015

J Virol

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“…In mathematics, chirality transfer in FRP is highlighted as an analogous strategy to construct polyhedral dice11. In life sciences, some virus capsids can be regarded as FRP12131415, in which each face of the icosahedral cricket paralysis virus capsid contains three quasi-equivalent subunits that form identical rotational directionality (Fig. 1b)14.…”

mentioning

confidence: 99%

“…In life sciences, some virus capsids can be regarded as FRP12131415, in which each face of the icosahedral cricket paralysis virus capsid contains three quasi-equivalent subunits that form identical rotational directionality (Fig. 1b)14. The transfer of 2D chirality of the building block to 3D chirality in FRP through self-assembly can be regarded as a type of emergent property161718.…”

mentioning

confidence: 99%

Assembled molecular face-rotating polyhedra to transfer chirality from two to three dimensions

Wang

Yang

et al. 2016

Nat Commun

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In nature, protein subunits on the capsids of many icosahedral viruses form rotational patterns, and mathematicians also incorporate asymmetric patterns into faces of polyhedra. Chemists have constructed molecular polyhedra with vacant or highly symmetric faces, but very little is known about constructing polyhedra with asymmetric faces. Here we report a strategy to embellish a C3h truxene unit with rotational patterns into the faces of an octahedron, forming chiral octahedra that exhibit the largest molar ellipticity ever reported, to the best of our knowledge. The directionalities of the facial rotations can be controlled by vertices to achieve identical rotational directionality on each face, resembling the homo-directionality of virus capsids. Investigations of the kinetics and mechanism reveal that non-covalent interaction among the faces is essential to the facial homo-directionality.

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“…A high level of disassembled capsid material has also been observed in EM grids of Triatoma virus [42]. Well defined particles did not show the obvious angular profile typical of picornavirus icosahedra reflecting the fact that dicistrovirus structures, while possessing icosahedral symmetry, are generally more spherical, shown classically for cricket paralysis virus [43] and more recently for Infectious flacherie virus [44] although projections around the 5 fold axes were observed in the recently solved Triatoma dicistrovirus structure [45].…”

Section: Resultsmentioning

confidence: 82%

“…Four strongly reactive antibodies, IAPVMAb8, IAPVMAb12, IAPVMAb17 and IAPVMAb27 were selected for formal epitope mapping using a library of 20 residue peptides overlapping by 10 made to the same IAPV VP2 sequence. Interestingly all four antibodies reacted with the N-terminal extended tail of VP2 visualised in the available dicistrovirus structures [43], [45]. Three antibodies co-mapped to the extreme N-terminal sequence TMPGDSQQES and one to an adjacent sequence ASSTSENSVE (Figure 5A).…”

Section: Resultsmentioning

confidence: 97%

Assembly of Recombinant Israeli Acute Paralysis Virus Capsids

et al. 2014

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The dicistrovirus Israeli Acute Paralysis Virus (IAPV) has been implicated in the worldwide decline of honey bees. Studies of IAPV and many other bee viruses in pure culture are restricted by available isolates and permissive cell culture. Here we show that coupling the IAPV major structural precursor protein ORF2 to its cognate 3C-like processing enzyme results in processing of the precursor to the individual structural proteins in a number of insect cell lines following expression by a recombinant baculovirus. The efficiency of expression is influenced by the level of IAPV 3C protein and moderation of its activity is required for optimal expression. The mature IAPV structural proteins assembled into empty capsids that migrated as particles on sucrose velocity gradients and showed typical dicistrovirus like morphology when examined by electron microscopy. Monoclonal antibodies raised to recombinant capsids were configured into a diagnostic test specific for the presence of IAPV. Recombinant capsids for each of the many bee viruses within the picornavirus family may provide virus specific reagents for the on-going investigation of the causes of honeybee loss.

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Untitled

Cited by 112 publications

References 45 publications

Structural Basis of Human Parechovirus Neutralization by Human Monoclonal Antibodies

Structural Basis of Human Parechovirus Neutralization by Human Monoclonal Antibodies

Assembled molecular face-rotating polyhedra to transfer chirality from two to three dimensions

Assembly of Recombinant Israeli Acute Paralysis Virus Capsids

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