Monoclonal antibodies that disrupt poliovirus only at fever temperatures

Delaet, Ingrid; Boeyé, Albert

doi:10.1128/jvi.67.9.5299-5302.1993

Cited by 14 publications

(2 citation statements)

References 19 publications

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“…Therefore, a simple steric effect in which antibody binds to the virion surface and blocks receptor attachment is sufficient to explain the neutralization behavior of many antibodies. Although some antibodies might induce secondary effects (e.g., causing conformational changes in the viral capsid) upon binding (12,27,30,60), such effects are not required for neutralization. In addition, antibodies that induce such secondary effects could not be exclusively selected for during B-cell clonal expansion.…”

Section: Mechanism Of Antibody-mediated Neutralization Of Hrv14mentioning

confidence: 99%

Antibody-Mediated Neutralization of Human Rhinovirus 14 Explored by Means of Cryoelectron Microscopy and X-Ray Crystallography of Virus-Fab Complexes

Che

Olson

Leippe

et al. 1998

J Virol

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The structures of three different human rhinovirus 14 (HRV14)-Fab complexes have been explored with X-ray crystallography and cryoelectron microscopy procedures. All three antibodies bind to the NIm-IA site of HRV14, which is the β-B–β-C loop of the viral capsid protein VP1. Two antibodies, Fab17-IA (Fab17) and Fab12-IA (Fab12), bind bivalently to the virion surface and strongly neutralize viral infectivity whereas Fab1-IA (Fab1) strongly aggregates and weakly neutralizes virions. The structures of the two classes of virion-Fab complexes clearly differ and correlate with observed binding neutralization differences. Fab17 and Fab12 bind in essentially identical, tangential orientations to the viral surface, which favors bidentate binding over icosahedral twofold axes. Fab1 binds in a more radial orientation that makes bidentate binding unlikely. Although the binding orientations of these two antibody groups differ, nearly identical charge interactions occur at all paratope-epitope interfaces. Nucleotide sequence comparisons suggest that Fab17 and Fab12 are from the same progenitor cell and that some of the differing residues contact the south wall of the receptor binding canyon that encircles each of the icosahedral fivefold vertices. All of the antibodies contact a significant proportion of the canyon region and directly overlap much of the receptor (intercellular adhesion molecule 1 [ICAM-1]) binding site. Fab1, however, does not contact the same residues on the upper south wall (the side facing away from fivefold axes) at the receptor binding region as do Fab12 and Fab17. All three antibodies cause some stabilization of HRV14 against pH-induced inactivation; thus, stabilization may be mediated by invariant contacts with the canyon.

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Section: Mechanism Of Antibody-mediated Neutralization Of Hrv14mentioning

confidence: 99%

Antibody-Mediated Neutralization of Human Rhinovirus 14 Explored by Means of Cryoelectron Microscopy and X-Ray Crystallography of Virus-Fab Complexes

Che

Olson

Leippe

et al. 1998

J Virol

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“…Studies have shown that virus dissociation can be influenced in vitro by physical disturbances, such as high pressure or extreme pH (10–12). Indeed, work on the picornaviruses has shown that binding of nAbs destabilizes the virion and releases the viral genome, even though the structural integrity of the resultant capsid is maintained (13–17). This raises the question as to whether a physical collision created while the antibody is engaged on the surface of the pathogen could eliminate the pathogen or render it harmless in situ.…”

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confidence: 99%

Viral neutralization by antibody-imposed physical disruption

Zheng

Jiang

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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In adaptive immunity, organisms produce neutralizing antibodies (nAbs) to eliminate invading pathogens. Here, we explored whether viral neutralization could be attained through the physical disruption of a virus upon nAb binding. We report the neutralization mechanism of a potent nAb 8C11 against the hepatitis E virus (HEV), a nonenveloped positive-sense single-stranded RNA virus associated with abundant acute hepatitis. The 8C11 binding flanks the protrusion spike of the HEV viruslike particles (VLPs) and leads to tremendous physical collision between the antibody and the capsid, dissociating the VLPs into homodimer species within 2 h. Cryo-electron microscopy reconstruction of the dissociation intermediates at an earlier (15-min) stage revealed smeared protrusion spikes and a loss of icosahedral symmetry with the capsid core remaining unchanged. This structural disruption leads to the presence of only a few native HEV virions in the ultracentrifugation pellet and exposes the viral genome. Conceptually, we propose a strategy to raise collision-inducing nAbs against single spike moieties that feature in the context of the entire pathogen at positions where the neighboring space cannot afford to accommodate an antibody. This rationale may facilitate unique vaccine development and antimicrobial antibody design.

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Update on the neutralisation of animal viruses

Dimmock

1995

Reviews in Medical Virology

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How a virus is neutralised depends upon several interacting factors. The most important of these, but by no means the only ones, are the interaction of a specific epitope, the properties of the cognate antibody, and the nature of the host cell. Variation in any one of these may change the mechanism by which neutralisation occurs and may obviate neutralisation altogether. The purpose of this article is to present an overview of neutralisation; for a more detailed discussion the reader should consult Dimmock' for references up to 1993 and more recent reviews2--' DEFINITIONSNeutralisation is the loss of infectivity which ensues when antibody molecule(s) bind to a virus particle, and usually occurs without the involvement of any other agency. As such this is an unusual activity of antibody paralleled only by the inhibition of toxins and enzymes. However, neutralisation by some antibodies may require or be assisted by, for example, complement or cells bearing receptors for the Fc portion of the antibody molecule. The term neutralisation is best used only in relation to in uifro systems as there is little information about how antibodies act in uiuo. The latter is defined here as protection. NEUTRALISATION EPITOPES Exposed epitopesMost epitopes are exposed and, in contrast to cryptic epitopes (see below), are available on the surface of a virion to bind antibody at all times. Most but not all viral neutralisation antigens are proteins. Figure I shows the relationship between epitope, antigenic site and antigen. An antigenic site is a collection of overlapping epitopes, but its definition is limited by the number of mAbs which are available for this purpose. In fact it is debatable whether or not discrete antigenic sites exist or' whether an antigen is a continuum of epitopes. However, the concept of an antigenic site highlights that there are regions of immunodominance to which the immune system responds by preference. Not all epitopes mediate Abbreviations used: CDR, complementary determining region. neutralisation. This is an important fact which emphasises that binding of antibody to an epitope is not in itself sufficient for neutralisation, and that neutralisation epitopes have the unique functional property which leads to loss of virus infectivity. This fact is further and very well demonstrated by some neutralising antibody-escape mutants which are still able to bind the selecting mAb (Table I; The epitope itself is unchanged, and it is likely that a mutation in another part of the molecule prevents neutralisation; this in turn implies that neutralisation via this epitope depends on the mAb being able to trigger an event within the neutralisation protein which occurs subsequent to binding. Cryptic epitopesAlthough postulated to occur some years ago, evidence for the existence of such epitopes has only recently been obtained. As their name indicates, cryptic epitopes are not normally available to bind antibody but are revealed by conformational changes in the virion which occur when it interacts with its environme...

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Monoclonal antibodies that disrupt poliovirus only at fever temperatures

Cited by 14 publications

References 19 publications

Antibody-Mediated Neutralization of Human Rhinovirus 14 Explored by Means of Cryoelectron Microscopy and X-Ray Crystallography of Virus-Fab Complexes

Antibody-Mediated Neutralization of Human Rhinovirus 14 Explored by Means of Cryoelectron Microscopy and X-Ray Crystallography of Virus-Fab Complexes

Viral neutralization by antibody-imposed physical disruption

Update on the neutralisation of animal viruses

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