Alteration of capsid proteins of coxsackievirus A13 by low ionic concentrations

Cords, Carl E.; James, C.; McLaren, Leroy C.

doi:10.1128/jvi.15.2.244-252.1975

Cited by 32 publications

(6 citation statements)

References 23 publications

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“…A second series of experiments was done in which the ability of chlorine-inactivated viruses to attach to host cells was compared with that of infective viruses since it has been shown that the loss of certain capsid components by enteroviruses or conformational changes impairs the ability of the viruses to attach to host cells (3,6). This possibility was eliminated by the results of the adsorption experiments (Table 1), which clearly show that the ability of chlorine-inactivated virus capsids to attach to HeLa cells was the same as that of infective virus preparations.…”

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confidence: 99%

Structural and compositional changes associated with chlorine inactivation of polioviruses

O’Brien¹,

Newman²

1979

Appl Environ Microbiol

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Chlorine inactivation of polioviruses resulted in the loss of viral ribonucleic acid, converting the viruses from 156S particles to 80S particles. However, it was found that virus inactivation occurred before the ribonucleic acid was released from the virions. Extraction of ribonucleic acid from partially inactivated virus suspensions indicated that chlorine inactivation was due to degradation of the ribonucleic acid before release and that ribonucleic acid loss was a secondary event. The empty 80S capsids had the same isoelectric point and ability to attach to host cells as infective virions. Thus, no major capsid conformational changes occurred during chlorine inactivation.

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confidence: 99%

Structural and compositional changes associated with chlorine inactivation of polioviruses

O’Brien¹,

Newman²

1979

Appl Environ Microbiol

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“…One study showed that treatment with fatty acid-free bovine serum albumin (BSA) converts echovirus 12 into A-particles, but the mechanism of action was not investigated further (21). In addition, there are only few studies reporting what effects other physiological factors, such as changes in ionic conditions, may have on the virus particle (21)(22)(23)(24)(25). X-ray crystallography as well as cryo-electron microscopy (cryoEM) and single particle reconstruction have been used to gain structural information on picornavirus particles at different stages before genome release (20,(26)(27)(28)(29)(30)(31)(32)(33).…”

mentioning

confidence: 99%

Extracellular Albumin and Endosomal Ions Prime Enterovirus Particles for Uncoating That Can Be Prevented by Fatty Acid Saturation

Ruokolainen

Domanska

Laajala

et al. 2019

J Virol

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There is limited information about the molecular triggers leading to the uncoating of enteroviruses under physiological conditions. Using real-time spectroscopy and sucrose gradients with radioactively labeled virus, we show at 37°C, the formation of albumin-triggered, metastable uncoating intermediate of echovirus 1 without receptor engagement. This conversion was blocked by saturating the albumin with fatty acids. High potassium but low sodium and calcium concentrations, mimicking the endosomal environment, also induced the formation of a metastable uncoating intermediate of echovirus 1. Together, these factors boosted the formation of the uncoating intermediate, and the infectivity of this intermediate was retained, as judged by end-point titration. Cryo-electron microscopy reconstruction of the virions treated with albumin and high potassium, low sodium, and low calcium concentrations resulted in a 3.6-Å resolution model revealing a fenestrated capsid showing 4% expansion and loss of the pocket factor, similarly to altered (A) particles described for other enteroviruses. The dimer interface between VP2 molecules was opened, the VP1 N termini disordered and most likely externalized. The RNA was clearly visible, anchored to the capsid. The results presented here suggest that extracellular albumin, partially saturated with fatty acids, likely leads to the formation of the infectious uncoating intermediate prior to the engagement with the cellular receptor. In addition, changes in mono- and divalent cations, likely occurring in endosomes, promote capsid opening and genome release. IMPORTANCE There is limited information about the uncoating of enteroviruses under physiological conditions. Here, we focused on physiologically relevant factors that likely contribute to opening of echovirus 1 and other B-group enteroviruses. By combining biochemical and structural data, we show that, before entering cells, extracellular albumin is capable of priming the virus into a metastable yet infectious intermediate state. The ionic changes that are suggested to occur in endosomes can further contribute to uncoating and promote genome release, once the viral particle is endocytosed. Importantly, we provide a detailed high-resolution structure of a virion after treatment with albumin and a preset ion composition, showing pocket factor release, capsid expansion, and fenestration and the clearly visible genome still anchored to the capsid. This study provides valuable information about the physiological factors that contribute to the opening of B group enteroviruses.

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“…In the case of poliovirus, conversion to 135S particles has been demonstrated in vitro by incubation of the virus with the solubilized receptor expressed in insect cells (23). Poliovirus and group A coxsackievirus 135S particles may also be produced simply by incubating the virus at elevated temperatures in hypotonic media in the presence of calcium (12,28,43).…”

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confidence: 99%

The poliovirus 135S particle is infectious

Curry

Chow

Hogle

1996

J Virol

125

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The molecular mechanism of cell entry by unenveloped viruses is poorly understood. The picornaviruses poliovirus, human rhinovirus, and coxsackievirus convert to an altered form (the 135S or A particle) upon interaction with receptors on susceptible cells at 37؇C. The 135S particle is thought to be a necessary intermediate because it accumulates inside susceptible cells soon after infection and drugs which inhibit conversion of the virus to this form also prevent infection. However, since a variable fraction of the altered 135S particles is reported to elute unproductively from the surface of susceptible cells, their precise role remains unclear. We have found that poliovirus 135S particles can infect Chinese hamster ovary (CHO) and murine L cells, neither of which are susceptible to infection by native poliovirus. The infectivity of the particles in tissue culture appears to be between 10 3 to 10 5 times less than that of poliovirus on HeLa cells. The 135S particle infectivity was not sensitive to RNase but was greatly reduced by proteolytic treatment. Proteolysis specifically removed the newly exposed N terminus of VP1, a feature which has previously been shown to mediate interactions of the particle with lipid membranes. These results demonstrate that although the infectivity of the 135S particle appears to be receptor independent, it nonetheless requires some property associated with the protein coat. In particular, the N terminus of VP1 plays an important role in the infection process. Our findings are consistent with the hypothesis that the 135S particle is an intermediate in the normal cell entry pathway of poliovirus infection.

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Alteration of capsid proteins of coxsackievirus A13 by low ionic concentrations

Cited by 32 publications

References 23 publications

Structural and compositional changes associated with chlorine inactivation of polioviruses

Structural and compositional changes associated with chlorine inactivation of polioviruses

Extracellular Albumin and Endosomal Ions Prime Enterovirus Particles for Uncoating That Can Be Prevented by Fatty Acid Saturation

The poliovirus 135S particle is infectious

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